LIVER TRANSPLANTATION

لقاء د سامى حبيب فى العاشره مساء الجزء الثانى

2011-09-22T20:29:00.000+02:00

لقاء د سامى حبيب فى العاشره مساء الجزء الاول.wmv

2011-09-22T19:18:00.000+02:00

Liver Transplant Complete Guide

2011-09-08T19:56:00.002+02:00

Liver Transplant Complete Guide

Before Liver Transplant
During Liver Transplant
After Liver Transplant
Medications

A number of diseases can directly damage the liver. Damage to the liver can seriously affect the absorption of vitamins and nutrients, prevent waste products from being effectively removed from the system, and reduce the production of proteins needed to clot the blood.

If the damage is severe enough, transplantation may be necessary. A transplant provides a patient with a liver that can keep up with the demands of a full, active life.

What the Liver Does

The liver is the largest organ in the body. It is located on the right side of the abdomen (to the right of the stomach) behind the lower ribs and below the lungs. The liver performs more than 400 functions each day to keep the body healthy. Some of its major jobs include:

• converting food into nutrients the body can use (for example, the liver produces bile to help break down fats)
• storing fats, sugars, iron, and vitamins for later use by the body
• making the proteins needed for normal blood clotting
• removing or chemically changing drugs, alcohol, and other substances that may be harmful or toxic to the body

Basic Functions of the Liver

The liver is the largest and one of the most complex organs in the body. It is located on the right side of the abdomen. The liver performs four basic functions:

• It aids in digestion by helping in the absorption of fat and certain vitamins, including vitamins A, D, E, and K
• It helps distribute the nutrients found in food
• It helps "clean" the blood by removing medications and toxins
• It produces important proteins that affect the blood, such as factorsthat are essential in making the blood clot after an injury.

The liver produces bile, which aids in the digestion and absorption of fats. Bile
also aids inthe absorption of substances such as vitamins A, D, E, and K and
medication that patients take as an immunosuppressive agent following liver
transplantation. The bile is stored in the gallbladder (which is located just below the liver) and then released into the intestines as needed. Together, these organs process the nutrients found in the foods we eat.
The liver also helps filter many chemical substances and waste products from the blood. Most medicines are cleaned from the bloodstream by the liver. The liver also removes any alcohol that's consumed.

Symptoms of Liver Disease

• jaundice (yellowing of eyes and skin)
• severe itching
• dark urine
• mental confusion or coma
• vomiting of blood
• easy bruising and tendency to bleed
• gray or clay-colored stools
• abnormal buildup of fluid in the abdomen

Before Liver Transplant

Pretransplant Evaluation
The Transplant Team
Preparing and Waiting for a Transplant

PRETRANSPLANT EVALUATION

Pretransplant tests, as well as giving a clear picture of the patient's overall health status, help in identifying potential problems before they occur. They also help in determining whether transplantation is truly the best option. This increases the likelihood of success.

The following procedures help in evaluating a patient's health status:

Chest x-ray - Determines the health of the patient's lungs and lower respiratory tract.

Electrocardiogram (EKG or ECG) - Determines how well the patient's heart is working and may reveal heart damage that was previously unsuspected.

Ultrasound with Doppler examination - Determines the openness of the bile ducts and major vessels. It is commonly done in all liver transplant recipients before and after transplantation.

CT (CAT) scan - This computerized image will show the size and shape of the patient's liver and major blood vessels.

MRI (magnetic resonance imaging) - May be used in place of CT scan or ultrasound to see inside the patient's body.

Total-body bone scan - If the patient has a liver tumor, ensures that it has not spread to his bones.

Blood tests - The patient's blood count, blood and tissue type, blood chemistries, and immune system function will all be checked. In addition, blood tests for certain infectious diseases will be performed.

Pulmonary function test - The patient will be asked to breathe into a tube attached to a measuring device, which will reveal how well his lungs are working and determine his blood's capacity to carry oxygen.

Hepatic angiograph - Dye injected into the patient's arteries will enable the transplant physician to see if there are any abnormalities or blockages in the patient's blood vessels.

Cholangiogram - Reveals any obstructions or growths in the patient's bile ducts.

Gallium, colloidal gold, or technetium scan - Gives the transplant physician a view of the patient's liver, gallbladder, and pancreas.

Peritoneoscopy - By inserting a flexible tube through a tiny incision in the patient's abdomen, the transplant physician will be able to see any structural changes in the liver.

Upper gastrointestinal (GI) series - This will show whether the patient's esophagus and stomach are disease free.

Lower GI series - Ensures that the patient is free of intestinal abnormalities.

Renal function studies - Urine may be collected from the patient for 24 hours in order to determine if the kidneys are working correctly. Blood tests such as serum creatinine are also performed to measure kidney function.

The Transplant Team

• Transplant Surgeon
• Transplant Physician (Hepatologist)
• Transplant Coordinator
• Nurse Practitioner
• Floor or Staff Nurse
• Physical Therapist • Floor or Staff Nurse
• Dietician
• Psychologist / Psychiatrist
• Pharmacist

Each of the skilled health care professionals who make up the transplant team take a personal interest in answering a patient's questions and taking care of his medical needs. They will also help the patient keep his spirits up along the way.
The patient is the most important member of the transplant team. To a certain extent, all the other team members will respond to his cues. The patient's physical, emotional, and practical needs will help them shape a personalized pretransplant and posttransplant treatment program.

Preparing and Waiting for A Liver Transplant

Days and weeks may pass while the transplant team waits?to locate the right liver for a specific patient. During this time, the patient should prepare as much as possible and take positive steps to deal with the stresses of waiting, always staying focused on reaching the goal of transplant.

During Liver Transplant

Getting the Go-Ahead
At the Hospital
Preparing the Patient for Surgery
Liver Transplant Surgery Procedure
T-Tube Placement and Bile Drainage

Getting the Go-Ahead

When that important phone call comes, the patient should make sure to bring the following to the hospital:

• A list of all the medications the patient is taking
• A list of the patient's drug allergies, if he has any
• The patient's health insurance information

IMPORTANT: As soon as a liver is available, the patient should stop all eating and drinking immediately. The patient's stomach must be empty when he is taken into the operating room.

At the Hospital

After admission, the patient will have a thorough physical examination, including more blood work, a chest x-ray, and EKG, and, possibly, other tests.

Unfortunately, surgery must be postponed in some cases. The patient will be sent home again if:

• he has an infection or has developed any other medical problem that would interfere with surgery or recovery
• The donor liver shows signs of deterioration or poor function

If surgery is postponed, the transplant team can help the patient through the disappointment. This is only a temporary setback, and the search for a new liver will go on.

Preparing the Patient for Surgery

The patient may receive an enema to clean out his intestines and prevent constipation after surgery. His chest and abdomen will be shaved clean to prevent infection, and an intravenous (IV) line will be inserted in his arm or just under his collarbone to give medication and keep him from getting dehydrated. The patient will also be given a sedative to help him relax and feel sleepy before going to the operating room.

IMPORTANT:
Because transplantation is a major surgical procedure, the patient may need a transfusion. Today, all blood is screened very carefully; the likelihood of contracting a disease is very small. Any concerns that the patient has regarding the source of the blood should be relayed to the transplant team during the waiting period, before getting to the hospital. Most hospitals offer the option of "autotransfusion" - this is when the patient donates his own blood before surgery. His own blood is stored and hen used during transplantation.

The Liver Transplant Surgery Procedure

The patient will be under general anesthesia throughout the surgery. Once asleep, the transplant surgeon will make an incision shaped like a boomerang on the upper part of the abdomen. The surgical team will then remove the patient's old liver, leaving portions of his major blood vessels in place. The new liver will then be inserted and attached to these blood vessels and to the patient's bile ducts. To help with bile drainage, a tube will also be inserted in the bile duct during surgery.

T-Tube Placement and Bile Drainage

During liver-transplant surgery, the surgeon may find it necessary to place a small tube, called a T-tube, into the bile duct. The T-tube allows bile to drain out of the patient's body into a small pouch, known as a bile bag. The amount of bile, which varies in color from deep gold to dark green, can then be measured. If a T-tube is put in place, it may remain attached to a bile bag for a week or possibly longer. When the bile bag is removed the T-tube will be tied or capped. It will remain in place for several months so that it can be used for special testing.

The T-tube is attached to the skin with a stitch. The dressing around the tube should be changed at least once daily, and more often if it becomes moist. The transplant nurse will show the patient how to change the dressing without pulling out the T-tube.

Other drains may be in the patient's abdomen during the postoperative period. A common name for these drains is Jackson-Pratt (JP). They are used to drain fluid from around the liver. Generally, these drains are removed before the patient goes home.

The surgical team will then place the donor kidney into the abdomen and connect the kidney's blood vessels to the recipient's iliac artery and vein. The surgeons will then connect the ureter to the bladder. A small drain, called a Jackson Pratt, may be placed into the abdominal cavity to drain any excess fluid.

After Liver Transplant

Waking Up in the Intensive Care Unit
Medical Management in the Acute Care Unit
Clinic and Follow-Up Visits
Lab Tests
Additional Tests and Procedures
Monitoring at Home
Resuming Normal Activities
Avoiding Infection
Communicating with the Healthcare Team

Waking Up in the Intensive Care Unit (ICU)

After the surgery, the patient will wake up in the intensive care unit after the anesthesia wears off.

This is what the patient should expect:

• Some pain and discomfort, which medication will help to relieve.
• A tube will be inserted through the patient's nose. This tube will run down the patient's throat and into his stomach. This tube will keep the stomach empty, to help prevent nausea and vomiting.
• A tube may be inserted into the patient's throat to help him get enough oxygen. It will be connected to a breathing machine called a ventilator. The patient should try to relax and let the machine breathe for him. The patient will not be able to talk with this tube in place, but he will only need it for a few days. Nurses will do everything they can to help the patient communicate. The patient's throat may feel sore or scratchy for a few days afterward.
• The patient will be asked to cough periodically to keep his lungs clear. If it hurts to cough, the patient should ask someone to support his abdomen.
• The patient will have an IV line in his arm or neck under the collarbone, which will be used to give fluids and medication for the first few days after surgery.
• For several days after surgery, the patient will have a catheter in his bladder to drain urine. He may feel uncomfortable, and may feel that he has to urinate constantly, but it is only temporary.
• During surgery, several drains will be placed in or near the incision. These drains will be removed 5 to 10 days after surgery.

Medical Management in the Acute Care Unit

After the patient's medical condition has stabilized, he will be transferred from the ICU to the acute care unit. During the patient's stay on this unit, his laboratory studies, medications, nutritional status and exercise tolerance will be monitored. As soon as the patient is able, discharge instructions will begin to prepare him for going home.

Clinic and Follow-up Visits

Upon leaving the hospital, the patient will receive a schedule of follow-up clinic visits for lab tests and checkups. The purpose is to track your progress and detect potential complications as early as possible.

On days when the patient is scheduled for follow-up visits, he should bring his medication list and his surgery handbook. He will be given specific instructions for routine lab work or special tests that he might need.

Lab Tests

A usual lab test monitors blood count, clotting, kidney function, liver function, electrolytes, and medication levels in the patient's blood. Other tests may be ordered as necessary.

Tests for BLOOD COUNT:

WBC tell if the patient's white blood cells have increased (usually a sign of infection) or decreased (indicating a lower defense against infection).
HCT measures the hematocrit, which is the percentage of red blood cells in the blood. Red blood cells carry oxygen to all parts of the body. When a patient's HCT is low, he may feel tired or have little energy.
PLTmeasures the level of platelets. Platelet cells form a blood clot when the body is injured. Low platelet levels may cause someone to bruise easily and to bleed for a longer time when injured.

Test for KIDNEY FUNCTION:

Creatinine and BUN tell how well the kidneys work by measuring levels of creatinine and blood urea nitrogen, waste products normally removed from the blood by the kidneys.

Tests for LIVER FUNCTION:

Bili measures the level of bilirubin, a normal byproduct when hemoglobin from red blood cells breaks down. The liver removes bilirubin from the blood and excretes it in the bile. When the liver is not functioning normally, bilirubin levels can increase, often resulting in jaundiced (yellowed) skin and eyes.
Alk Phos measures alkaline phosphatase, which is made in the bones, liver, pancreas, and intestines and removed from the blood by the liver.
AST, ALT, and GGTP test enzymes that are made in the liver. These tests tell how well the liver is working. K measures potassium, which is needed for normal heart and muscle function.

Tests for ELECTROLYTES (dissolved minerals):

Ca measures calcium, which is necessary for strong bones and teeth, blood clotting, and heart and nerve function. NOTE: The desired level (normal range) will differ for each person, depending on the combination of immunosuppressive medications and the length of time since the transplant.
PO4 measures phosphate, which works closely with calcium to strengthen bones.
Mg measures magnesium, which is necessary for normal functioning of muscles and for blood clotting.
K measures potassium, which is needed for normal heart and muscle function.
Na measures sodium, which helps maintain the balance of salt and water in the body.

Other blood tests:

Drug levels measure PROGRAF or SANDIMMUME in the blood. PROGRAF or SANDIMMUNE blood levels must be checked regularly to avoid levels that are too high or too low. High levels could lead to toxicity or over-immunosuppression, and low levels may lead to rejection.
NOTE: The desired level (normal range) will differ for each person, depending on the combination of immunosuppressive medications and the length of time since the transplant.
Glu measures glucose, levels of sugar in the blood; some medications may produce a diabetes-like condition in which blood-sugar levels are too high.

Additional Tests and Procedures

The transplant team may perform one or more of the following tests and procedures to monitor a patient's transplant:

Ultrasound - This test is performed to make sure all the main blood vessels leading to the liver are functioning normally. This test is also used to check for collections of fluid, such as blood or bile. The procedure consists of placing a cool gel on the patient's abdomen, over which a wand (transducer) is moved to transmit sound waves. These are converted into images of the liver and projected onto a television screen.

Percutaneous transhepatic cholangiogram (PTC) - This is an X ray that shows the patient's bile ducts to check for leaks, blockages, or other potential problems. The procedure starts with a dye injection into the T-tube. The dye makes the ducts easy to see on X ray. If a T-tube was not placed during your surgery, this X ray will be performed after dye has been injected directly into the liver-bile ducts.

Liver biopsy (test sample) This test is usually performed to check for rejection, hepatitis, or other possible problems. This may be done in the hospital or in the outpatient/short-stay unit. The patient will receive special instructions regarding the procedure. Before the procedure, the patient will receive a numbing injection (local anesthetic) on the right side of his abdomen. Then a special needle will be inserted to withdraw a small sample of liver tissue that will be examined with a microscope. After this procedure, the patient must lie on his right side for at least 1 hour and stay in bed for about 4 hours.

Computerized tomography (CT) scan - This is a type of X ray that allows the physician to view the patient's liver from many different angles to detect infections, fluid collections, or other problems. The procedure requires that the patient drink a liquid that outlines his stomach and intestines and makes his liver more visible; then he lies flat for 1 hour while the machine takes X rays around him.

Magnetic resonance imaging (MRI) - This is another type of test that produces an image. Somewhat like a CT scan, it also allows a patient's liver to be viewed from different angles and in three-dimensional images. An MRI shows soft tissues, such as the liver, more clearly than a CT scan does.

Endoscopic retrograde cholangiopancreatogram (ERCP) - This test allows the physician to see the patient's biliary tree (the various ducts in and around the liver), as well as the ducts from the pancreas. The patient will be given medicine to relax him before the procedure. An endoscope (a type of tube) is placed in his mouth; it is advanced through to his stomach and into his intestine to the liver. A dye is then infected through the endoscope that makes the ducts visible in X rays.

Monitoring Health and A New Liver at Home

After a patient is discharged from the hospital, he may be asked to monitor:

Temperature - A patient should check and record temperature any time he feels chilled, hot, achy, or ill. This may be the first sign of infection.

WARNING: DO NOT USE TYLENOLR, ADVILR (Ibuprofen), aspirin, or other such products except under the direction of a physician, as these drugs may cause further symptoms.

If a patient's temperature is higher than normal at any time, he should notify his transplant coordinator immediately. This is considered an emergency, because an elevated temperature could indicate a serious infection or rejection.

Blood pressure - A nurse or transplant coordinator will show how to measure blood pressure, if necessary. The top number (systolic) is noted at the first sound, and the bottom number (diastolic) is noted when the sound changes (not stops). It is important that a patient knows his normal blood pressure, normal changes, and when he should be concerned.

Pulse - If a patient is taking medication that affects heart rate, the nurse or coordinator will show how to check his own pulse at home.

NOTE: If a patient experiences chest pain or has difficulty breathing, he should call 911 for an ambulance and go to the nearest emergency room. He SHOULD NOT attempt to drive himself.

Weight - The patient may weigh himself on a standard bathroom scale at the same time every morning (after going to the toilet). If he gains more than 2 pounds per day, he could be retaining fluid. This should be reported to the transplant coordinator.

Resuming Normal Activities

Although the patient is encouraged to resume normal activities after recovery, it is important to understand that having a new liver brings new responsibilities.

• Skin and Hair Care
• Sexual Activity
• Smoking
• Vacations and Travel
• Dental Care
• Pregnancy
• Exercise
• Diet and Nutrition
• Alcoholic Beverages

Signs to Watch Out For

While primary concerns involve infection and rejection, many other problems, such as colds or flu, adjustment of other medications, and minor infections can be handled by a local physician. A patient needs to take precautions and learn to watch for signs of infection and rejection that necessitate notifying a local physician or transplant team immediately. These include:

• a fever that continues for more than 2 days
• shortness of breath
• a cough that produces a yellowish or greenish substance
• a dry cough that continues for more than 1 week
• prolonged nausea, vomiting, or diarrhea
• an inability to take prescribed medication
• bleeding, bruising, black stools, red or rusty-brown urine
• a rash or other skin changes
• pain, discharge, or swelling at the T-tube site
• vaginal discharge or itching
• burning discomfort with urination
• exposure to mumps, measles, chicken pox, or shingles
• unusual weakness or light-headedness
• emergency-room treatment or hospitalization

Avoiding Infection

Because immunosuppressive medications interfere with a patient's natural immune system, he needs to protect himself consciously from infection after the surgery by taking the following precautions:

• Wash hands often.
• Keep hands away from face and mouth.
• Stay away from people with colds or other infections.
• Ask friends to visit only when they are well.
• If the patient has a wound and must change his own dressing, wash hands before and after.
• Wash hands after coughing or sneezing, and throw tissues into the trash immediately.
• If someone in the patient's family becomes ill with a cold of flu, have that individual follow normal precautions (use separate drinking glasses, covering their mouths when coughing, etc.)
• Avoid working in the soil for 6 months after the transplant. Thereafter, wear gloves.
• Avoid handling animal waste and avoid contact with animals who roam outside. Do not clean bird cages or fish or turtle tanks or cat litter. The cat litter box should be covered and taken out of a patient's home before it is changed.
• Avoid vaccines that consist of live viruses, such as Sabin oral polio, measles, mumps, German measles, yellow fever, or smallpox. The live virus can cause infections. If a patient or any family member intends to receive any vaccinations, they should notify the transplant team or local physician.

SPECIAL WARNING TO PARENTS OF CHILDREN WHO HAVE HAD TRANSPLANTS:

Ask the school nurse or other official to notify you immediately of any communicable diseases (for example, measles, chicken pox) that may be circulating in your school.

Communicating with the Healthcare Team

Communication and cooperation between the transplant team, local physician, pharmacist, dentist, and the patient himself is vital to his well-being. Having a transplanted liver and taking the medications needed to prevent rejection put a patient at risk for a number of complications. It is important to follow the instructions that will help prevent or lessen complications.

One of a patient's most important jobs is to make certain that all members of his local healthcare team - family physician, dentist, local pharmacist, and any other healthcare professionals he sees - are aware of the transplant, the medications he takes each day, and the precautions he must follow to stay healthy. Each of his local healthcare providers should be given the telephone number of his transplant team. He should ask that they contact the transplant center for specific information.

Anxiety and Depression

A serious procedure such as the one just experienced can create many personal and family stresses. It is not uncommon for transplant patients to experience anxiety and perhaps depression following their surgery, hospital confinement, and return home. To help a patient adjust to life at home and an eventual return to work or school, counseling and support group services are available. The patient should consult the transplant social worker or coordinator for information regarding services available to help resolve stress and anxiety.

Medications

Medication Guidelines
Postoperative Complications

Medication Guidelines

The patient is responsible for taking the medications that have been prescribed for him. He should talk to his physician, pharmacist, transplant nurse, and/or coordinator to understand fully:

• the name and purpose of each medication
• when to take each medication
• how to take each medication
• how long to continue taking each medication
• principal side effects of each medication
• what to do if he forgets to take a dose
• when to order more medication so it doesn't run out
• how to order or obtain medications
• what to avoid while taking medications

At home, the recovering patient will continue taking most of the medicines he began taking in the hospital after the transplant surgery, especially the anti-rejection medications. His immune system recognizes the new liver as foreign and will try to reject it. Therefore, his immune system must be controlled with immunosuppressive medications. The patient probably will have to take one or more of these drugs for the rest of his life, in addition to other medications.

REMINDER : Never stop taking medication or change the dosage without a physician's approval.

Before taking medications:

• Ask the nurse, coordinator, or pharmacist to help in selecting the best times to take medications.
• Try to take each medication at the same time every day.
• Follow a written schedule.
• DO NOT cut or crush a tablet unless advised to do so.

Storing medications

• Keep medications in the original container, tightly capped. If a special container is used to hold the pills, keep the container tightly sealed.
• Store in a cool, dry place away from direct sunlight.
• Do not store medications in the bathroom -- moisture can cause medications to lose their strength.
• Do not allow liquid medications to freeze.
• Do not store medications in the refrigerator unless the physician or pharmacist advises to do so.
• Keep all medications away from children.

Postoperative Complications

A number of postoperative complications are possible:

• Infection of the T-tube site and dislodgment of the T-tube
• Bile leak and biliary stenosis (narrowing of the bile duct)
• Infections
• High blood pressure
• Rejection
• Diabetes

There is no way to predict accurately which patients will have problems. The transplant team will do their best to reduce the likelihood of complications and to treat them promptly if they occur. Following instructions carefully and keeping the transplant team informed of any difficulties will help a patient return quickly to a normal, active life.

A patient should notify the transplant team if he:

• has prolonged illness (nausea, vomiting, diarrhea)
• is unable to take medicines by mouth due to illness
• thinks the directions on the label may be different from what he was told
• has trouble removing child-resistant caps
• has a reason to take aspirin, TYLENOLR (acetaminophen), other pain relievers, cold remedies, or diet pills
• feels he is having a reaction to the medications
• has had a change in health or eating habits
• has a new prescription from his local doctor or a change in a current prescription
• experiences any unusual symptoms or side effects, as they may be related to the medications he is taking
• is undergoing dental work of any kind

الكبد الدهنى

2009-07-08T22:06:00.003+03:00

الكبد الدهنى

ما هو الكبد الدهني؟

زيادة الدهون في خلايا الكبد بحيث تزيد الدهون في الكبد على 5 % من وزنه

ما هي أسباب حدوث الكبد الدهني ؟

الأسباب المشهورة التي تؤدي للكبد الدهني هي

تناول المشروبات الكحولية .

السمنة وزيادة الوزن .

مرض السكر .

زيادة الدهون في الدم .

سوء التغذية .

بعض الأدوية مثل أقراص منع الحمل .

ما هي أعراض الكبد الدهني ؟

عادة لا يؤدي الكبد الدهني لأي أعراض ولكن في أحوال قليلة قد يحس المريض بألم بسيط في الجزء الأيمن العلوي من البطن

كيف يتم تشخيص حالات الكبد الدهني ؟

يتم اكتشاف الحالة عندما يفحص الطبيب المريض لأي سبب من الأسباب فيجد عنده تضخم بالكبد فيقوم بطلب أشعه بالموجات الصوتية للبطن وهنا قد يقوم بعض الأطباء بالتشخيص أن الحالة دهون على الكبد ولكن هذا التشخيص غير دقيق لأن التهاب الكبد يؤدي لنفس الصورة بالضبط لذلك فان تشخيص دهون على الكبد يعتمد أساسا على فحص عينة من خلايا الكبد يتبين بها وجود نسبة الدهون فيها

ما هى الأبحاثات المطلوبه للكبد الدهني ؟

أشعه بالموجات الصوتية للبطن

تحليل وظائف الكبد ( أنزيمات الكبد ) حيث إنها قد ترتفع بشكل بسيط في حالات الكبد الدهني ولكنها ترتفع بشكل أكبر في حالة التهاب الكبد

التحاليل الخاصة بالفيروسات (س ؛ ب) ليعرف إذا كان المريض مصابا بالفيروسات الكبدية أم لا

تحليل الأجسام المضادة لتشخيص حالات التهاب الكبد المناعي

تحليل عينة من خلايا الكبد للتفرقة بين التهاب الكبد والكبد الدهن

هل هناك خطورة من الكبد الدهني ؟

أغلب حالات الكبد الدهني ليس لها خطورة أو مضاعفات فقد يتم الشفاء الكامل لهم

ولكن وجد حديثا أن بعض حالات الكبد الدهنى نادرا ما قد يصاحبها التهاب بالكبد او قد يحدث بها تليف للكبد

ما هو علاج الكبد الدهني ؟

-يتم علاج السبب أولا بمعنى

يتوقف المريض عن تناول المشروبات الكحولية

التغذية الصحيحه للمرضى الذين يعانون من سوء التغذية

عمل نظام غذائي لتقليل مرض السمنة وزيادة الوزن

علاج مرض السكر

إعطاء أدوية لتقليل الدهون في الدم في المرضى الذين يعانون من زيادتها

وبالإضافة إلى هذا يتم إعطاء المريض مضادات الأكسدة التي تحافظ على خلايا الكبد وينصح المريض بتناول الخضراوات الطازجة والفاكهة حيث إنها تحتوي على الكثير من مضادات الأكسدة وتساعد على تنظيم الوزن

GB VIRUS C (GBV-C)

2009-07-07T22:28:00.001+03:00

GB virus C (GBV-C) is a species of virus in the Flaviviridae family which has not yet been assigned to a genus, is known to infect humans, but is not known to cause human disease.
There have been reports that HIV patients coinfected with GBV-C can survive longer than those without GBV-C, but the patients may be different in other ways.
There is current active research into the virus' effects on the immune system in patients coinfected with GBV-C and HIV

History

Hepatitis G virus and GB virus C (GBV-C) are RNA viruses that were independently identified in 1995, and were subsequently found to be two isolates of the same virus.
Although GBV-C was initially thought to be associated with chronic hepatitis, extensive investigation failed to identify any association between this virus and any clinical illness.

Taxonomy

GBV-C is a member of the Flaviviridae family and is phylogenetically related to hepatitis C virus but appears to replicate primarily in lymphocytes, and poorly if at all in hepatocytes.
GBV-A and GBV-B are probably Tamarin viruses, while GBV-C infects humans.

Human infection

The majority of immune-competent individuals appear to clear GBV-C viraemia within the first few years following infection and although the time interval between GBV-C infection and clearance of viraemia (detection of GBV-C RNA in plasma) is not known, infection may persist for decades in some individuals.
Approximately 2% of healthy US blood donors are viraemic with GBV-C, and up to 13% of blood donors have antibodies to E2 protein, indicating prior infection.
Parenteral, sexual and vertical transmission of GBV-C have all been documented, and because of shared modes of transmission, individuals infected with HIV are commonly co-infected with GBV-C. Among people with HIV infection, the prevalence of GBV-C viraemia ranges from 14 to 43%.
Some studies have suggested that co-infection with GBV-C will actually slow the progression of HIV disease.

HEPATITIS F

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Hepatitis F is a hypothetical virus linked to hepatitis. Several hepatitis F candidates emerged in the 1990s; none of these reports have been substantiated.
Most recently, in 1994 Deka et al. reported that novel viral particles had been discovered in the stool of post-transfusion, non-hepatitis A, non-hepatitis B, non-hepatitis C, non-hepatitis E patients.
Injection of these particles, into the bloodstream of Indian rhesus monkeys caused hepatitis, and the virus was named hepatitis F, or Toga virus.
Further investigations failed to confirm the existence of the virus, and it was delisted as a cause for infectious hepatitis.
A subsequently-discovered virus thought to cause hepatitis was named Hepatitis G, though its role in hepatitis has not been confirmed and it is now considered synonymous with GB virus C and is an "orphan virus" with no causal links to any human disease

HEPATITIS E

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Hepatitis E is a viral hepatitis (liver inflammation) caused by infection with a virus called hepatitis E virus (HEV).
HEV virus is a positive-sense single-stranded RNA icosahedral virus with a 7.5 kb genome.
HEV has a fecal-oral transmission route.
Infection with this virus was first documented in 1955 during an outbreak in New Delhi, India.

Molecular biology

Although it was originally classified in the Caliciviridae family, the virus has since been classified into the genus Hepevirus of the family Hepeviridae. The virus itself is a small non-enveloped particle.
The genome is approximately 7200 bases in length, is a polyadenylated single-strand RNA molecule that contains three discontinuous and partially overlapping open reading frames (ORFs) along with 5' and 3' cis-acting elements, which have important roles in HEV replication and transcription. ORF1 encode a methyltransferase, protease, helicase and replicase; ORF2 encode the capsid protein and ORF3 encodes a protein of undefined function.
There are currently (2009) approximately 1,600 sequences of HEV that are already available of both human and animal isolates.
Although there is one serotype of this virus, four distinct genotypes have been reported. Genotypes 1 and 2 are restricted to humans and often associated with large outbreaks and epidemics in developing countries with poor sanitation conditions.
Genotypes 3 and 4 infect humans, pigs and other animal species and have been responsible for sporadic cases of hepatitis E in both developing and industrialized countries.
An avian virus has been described that is associated with Hepatitis-Splenomegaly syndrome in chickens.
This virus is genetically and antigenically related to mammalian HEV and probably represents a new genus in the family.
Replicative virus has been found in the small intestine, lymph nodes, colon as well as the liver of experimentally infected pigs.
An in vitro culture system is not yet available.
Despite this difficulty a number of vaccine candidates are under investigation.

Epidemiology

The incidence of hepatitis E is highest in adults between the ages of 15 and 40.
Though children often contract this infection as well, they less frequently become symptomatic. Mortality rates are generally low, for Hepatitis E is a “self-limiting” disease, in that it usually goes away by itself and the patient recovers.
However, during the duration of the infection (usually several weeks), the disease severely impairs a person’s ability to work, care for family members, and obtain food.
Hepatitis E occasionally develops into an acute severe liver disease, and is fatal in about 2% of all cases.
Clinically, it is comparable to hepatitis A, but in pregnant women the disease is more often severe and is associated with a clinical syndrome called fulminant hepatic failure.
Pregnant women, especially those in the third trimester, suffer an elevated mortality rate from the disease ~20%.

Patterns

Hepatitis E is prevalent in most developing countries, and common in any country with a hot climate.
It is widespread in Southeast Asia, northern and central Africa, India, and Central America.
It is spread mainly through fecal contamination of water supplies or food; person-to-person transmission is uncommon.
Outbreaks of epidemic Hepatitis E most commonly occur after heavy rainfalls and monsoons because of their disruption of water supplies.
Major outbreaks have occurred in New Delhi, India (30,000 cases in 1955-1956), Burma (20,000 cases in 1976-1977), Kashmir, India (52,000 cases in 1978), Kanpur, India (79,000 cases in 1991), and China (100,000 cases between 1986 and 1988).

Animals as a reservoir

Domestic animals have been reported as a reservoir for the hepatitis E virus, with some surveys showing infection rates exceeding 95% among domestic pigs.
Transmission after consumption of wild boar meat and uncooked deer meat has been reported as well.
The rate of transmission to humans by this route and the public health importance of this are however still unclear.
A number of rodents have been identified as potential reservoirs: the Lesser Bandicoot Rat (Bandicota bengalensis), the Black Rat (Rattus rattus brunneusculus) and the Asian House Shrew (Suncus murinus).

Recent outbreaks

In 2004, there were two major outbreaks, both of them in sub-Saharan Africa.
There was an outbreak in Chad in which, as of September 27 there were 1,442 reported cases and 46 deaths.
In Sudan, which has been troubled with conflict recently (see, Darfur conflict), they are also suffering from a severe Hepatitis E epidemic.
As of September 28, there were 6,861 cases and 87 deaths, mainly in the West Darfur Region.
UNICEF, Doctors Without Borders, the Red Cross, and other international health organizations are currently working to increase the availability of soap, dig new wells, and chlorinate water supplies and reserves. However, the existing resources are still not enough, and more personnel and funds are severely needed in the region to assure the health and welfare of the people.
Increasingly, hepatitis E is being seen in developed nations with reports of cases in the UK, US and Japan. The disease is thought to be a zoonosis in that animals are thought to be the source. Both deer and pigs have been implicated.

Prevention

Improving sanitation is the most important measure, which consists of proper treatment and disposal of human waste, higher standards for public water supplies, improved personal hygiene procedures and sanitary food preparation.
Thus, prevention strategies of this disease are similar to those of many others that plague developing nations, and they require large-scale international financing of water supply and water treatment projects.
A vaccine based on recombinant viral proteins has been developed and recently tested in a high-risk population (military personnel of a developing country).
The vaccine appeared to be effective and safe, but further studies are needed to assess the long-term protection and the cost-effectiveness of hepatitis E vaccination.

HEPATITIS D

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Hepatitis D, also referred to as Hepatitis D virus (HDV) and classified as Hepatitis delta virus, is a disease caused by a small circular RNA virus.
HDV is considered to be a subviral satellite because it can propagate only in the presence of another virus, the Hepatitis B virus (HBV).
Transmission of HDV can occur either via simultaneous infection with HBV (coinfection) or via infection of an individual previously infected with HBV (superinfection).
Both superinfection and coinfection with HDV results in more severe complications compared to infection with HBV alone.
These complications include a greater likelihood of experiencing liver failure in acute infections and a greater likelihood of developing liver cancer in chronic infections.
In combination with hepatitis B virus, hepatitis D has the highest mortality rate of all the hepatitis infections of 20%.

Genome

The HDV genome exists as a negative sense, single-stranded, closed circular RNA.
Because of a nucleotide sequence that is 70% self-complementary, the HDV genome forms a partially double stranded RNA structure that is described as rod-like.
With a genome of approximately 1700 nucleotides, HDV is the smallest "virus" known to infect animals.
It has been proposed that HDV may have originated from a class of plant viruses called viroids.
Evidence in support of this hypothesis stems from the fact that both HDV and viroids exist as single-stranded, closed circular RNAs that have rod-like structures.
Likewise, both HDV and viroids contain RNA sequences that can assume catalytically active structures called ribozymes.
During viral replication, these catalytic RNAs are required in order to produce unit length copies of the genome from longer RNA concatamers.
Finally, neither HDV nor viroids encode their own polymerase.
Instead, replication of HDV and viroids requires a host polymerase that can utilize RNA as a template.
RNA polymerase II has been implicated as the polymerase responsible for the replication of HDV.
Normally RNA polymerase II utilizes DNA as a template and produces mRNA.
Consequently, if HDV indeed utilizes RNA polymerase II during replication, it would be the only known pathogen capable of using a DNA-dependent polymerase as an RNA-dependent polymerase.

Delta antigens

A significant difference between viroids and HDV is that, while viroids produce no proteins, HDV produces two proteins called the small and large delta antigens (HDAg-S and HDAg-L, respectively).
These two proteins are produced from a single open reading frame.
They are identical for 195 amino acids and differ only by the presence of an additional 19 amino acids at the C-terminus of HDAg-L. Despite having 90% identical sequences, these two proteins play diverging roles during the course of an infection.
HDAg-S is produced in the early stages of an infection and is required for viral replication.
HDAg-L, in contrast, is produced during the later stages of an infection, acts as an inhibitor of viral replication, and is required for assembly of viral particles.

Transmission

HDV is rare in most developed countries, and is mostly associated with intravenous drug abuse.
However HDV is much more common in Mediterranean countries, sub-Saharan Africa, the Middle East, and countries in the northern part of South America.
In all, about 20 million people may be infected with HDV.

HEPATITIS C

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The hepatitis C virus (HCV) is spread by blood-to-blood contact.
Most people have few, if any symptoms after the initial infection, yet the virus persists in the liver in about 85% of those infected.
Persistent infection can be treated with medication, peginterferon and ribavirin being the standard-of-care therapy.
Only 51% are cured overall.
Those who develop cirrhosis or liver cancer may require a liver transplant, and the virus universally recurs after transplantation.
An estimated 270-300 million people worldwide are infected with hepatitis C.
Hepatitis C is a strictly human disease.
It cannot be contracted from or given to any animal.
Chimpanzees are able to carry the disease for lab work, but the animals do not get sick.
The inability to perform animal testing has severely limited attempts to study and cure the disease in a nonhuman in vivo environment.
No vaccine against hepatitis C is available.
The existence of hepatitis C (originally "non-A non-B hepatitis") was postulated in the 1970s and proved conclusively in 1989.
It is one of five known hepatitis viruses: A, B, C, D, and E.

Signs and symptoms

Acute

Acute hepatitis C refers to the first 6 months after infection with HCV.
Between 60% to 70% of people infected develop no symptoms during the acute phase.
In the minority of patients who experience acute phase symptoms, they are generally mild and nonspecific, and rarely lead to a specific diagnosis of hepatitis C.
Symptoms of acute hepatitis C infection include decreased appetite, fatigue, abdominal pain, jaundice, itching, and flu-like symptoms.
The hepatitis C virus is usually detectable in the blood within one to three weeks after infection by PCR, and antibodies to the virus are generally detectable within 3 to 15 weeks.
Up to 50% of persons infected with HCV clear the virus from their bodies during the acute phase as shown by normalization in liver enzymes (alanine transaminase (ALT) & aspartate transaminase (AST)), as well as plasma HCV-RNA clearance (this is known as spontaneous viral clearance).
The remaining 60-85% of patients infected with HCV develop chronic hepatitis C, i.e., infection lasting more than 6 months.
Previous practice was to not treat acute infections to see if the person would spontaneously clear; recent studies have shown that treatment during the acute phase of genotype 1 infections has a greater than 90% success rate with half the treatment time required for chronic infections.

Chronic

Chronic hepatitis C is defined as infection with the hepatitis C virus persisting for more than six months.
Clinically, it is often asymptomatic (without symptoms) and it is mostly discovered accidentally.
The natural course of chronic hepatitis C varies considerably from one person to another. Although almost all people infected with HCV have evidence of inflammation on liver biopsy the rate of progression of liver scarring (fibrosis) shows significant variability among individuals. Accurate estimates of the risk over time are difficult to establish because of the limited time that tests for this virus have been available.
Recent data suggest that among untreated patients, roughly one-third progress to liver cirrhosis in less than 20 years. Another third progress to cirrhosis within 30 years.
The remainder of patients appear to progress so slowly that they are unlikely to develop cirrhosis within their lifetimes.
In contrast the NIH consensus guidelines state that the risk of progression to cirrhosis over a 20-year period is 3-20 percent.
Factors that have been reported to influence the rate of HCV disease progression include age (increasing age associated with more rapid progression), gender (males have more rapid disease progression than females), alcohol consumption (associated with an increased rate of disease progression), HIV coinfection (associated with a markedly increased rate of disease progression), and fatty liver (the presence of fat in liver cells has been associated with an increased rate of disease progression).
Symptoms specifically suggestive of liver disease are typically absent until substantial scarring of the liver has occurred. However, hepatitis C is a systemic disease and patients may experience a wide spectrum of clinical manifestations ranging from an absence of symptoms to a more symptomatic illness prior to the development of advanced liver disease. Generalized signs and symptoms associated with chronic hepatitis C include fatigue, flu-like symptoms, joint pains, itching, sleep disturbances, appetite changes, nausea, and depression.
Once chronic hepatitis C has progressed to cirrhosis, signs and symptoms may appear that are generally caused by either decreased liver function or increased pressure in the liver circulation, a condition known as portal hypertension.
Possible signs and symptoms of liver cirrhosis include ascites (accumulation of fluid in the abdomen), bruising and bleeding tendency, varices (enlarged veins, especially in the stomach and esophagus), jaundice, and a syndrome of cognitive impairment known as hepatic encephalopathy.
Hepatic encephalopathy is due to the accumulation of ammonia and other substances normally cleared by a healthy liver.
Liver enzyme tests show variable elevation of ALT and AST.
Periodically they might show normal results.
Usually prothrombin and albumin results are normal, but may become abnormal, once cirrhosis has developed.
The level of elevation of liver tests do not correlate well with the amount of liver injury on biopsy.
Viral genotype and viral load also do not correlate with the amount of liver injury.
Liver biopsy is the best test to determine the amount of scarring and inflammation.
Radiographic studies such as ultrasound or CT scan do not always show liver injury until it is fairly advanced.
Chronic hepatitis C, more than other forms of hepatitis, can be associated with extrahepatic manifestations associated with the presence of HCV such as porphyria cutanea tarda, cryoglobulinemia (a form of small-vessel vasculitis) and glomerulonephritis (inflammation of the kidney), specifically membranoproliferative glomerulonephritis (MPGN).
Hepatitis C is also rarely associated with sicca syndrome (an autoimmune disorder), thrombocytopenia, lichen planus, diabetes mellitus and with B-cell lymphoproliferative disorders.

Virology

The Hepatitis C virus (HCV) is a small (50 nm in size), enveloped, single-stranded, positive sense RNA virus. It is the only known member of the hepacivirus genus in the family Flaviviridae. There are six major genotypes of the hepatitis C virus, which are indicated numerically (e.g., genotype 1, genotype 2, etc.).
The hepatitis C virus (HCV) is transmitted by blood-to-blood contact.
In developed countries, it is estimated that 90% of persons with chronic HCV infection were infected through transfusion of unscreened blood or blood products or via injecting drug use or sexual exposure.
In developing countries, the primary sources of HCV infection are unsterilized injection equipment and infusion of inadequately screened blood and blood products. There has not been a documented transfusion-related case of hepatitis C in the United States for over a decade as the blood supply is vigorously screened with both EIA and PCR technologies.
Although injection drug use is the most common routes of HCV infection, any practice, activity, or situation that involves blood-to-blood exposure can potentially be a source of HCV infection.
The virus may be sexually transmitted, although this is rare, and usually only occurs when an STD that causes open sores and bleeding is also present and makes blood contact more likely.

Transmission

Several activities and practices were initially identified as potential sources of exposure to the hepatitis C virus. More recent studies question this route of transmission.
Currently it is felt to be a means of rare transmission of hepatitis C infection.
Injection drug use
Those who currently use or have used drug injection as their delivery route for drugs are at increased risk for getting hepatitis C because they may be sharing needles or other drug paraphernalia (includes cookers, cotton, spoons, water, etc.), which may be contaminated with HCV-infected blood. An estimated 60% to 80% of intravenous recreational drug users in the United States have been infected with HCV.
Harm reduction strategies are encouraged in many countries to reduce the spread of hepatitis C, through education, provision of clean needles and syringes, and safer injecting techniques.
For reasons that are not clear transmission by this route currently appears to be declining in the US.
Blood products
Blood transfusion, blood products, or organ transplantation prior to implementation of HCV screening (in the U.S., this would refer to procedures prior to 1992) is a decreasing risk factor for hepatitis C.
The virus was first isolated in 1989 and reliable tests to screen for the virus were not available until 1992.
Therefore, those who received blood or blood products prior to the implementation of screening the blood supply for HCV may have been exposed to the virus.
Blood products include clotting factors (taken by hemophiliacs), immunoglobulin, Rhogam, platelets, and plasma.
In 2001, the Centers for Disease Control and Prevention reported that the risk of HCV infection from a unit of transfused blood in the United States is less than one per million transfused units.
Iatrogenic medical or dental exposure
People can be exposed to HCV via inadequately or improperly sterilized medical or dental equipment. Equipment that may harbor contaminated blood if improperly sterilized includes needles or syringes, hemodialysis equipment, oral hygiene instruments, and jet air guns, etc.
Scrupulous use of appropriate sterilization techniques and proper disposal of used equipment can reduce the risk of iatrogenic exposure to HCV to virtually zero.
Occupational exposure to blood
Medical and dental personnel, first responders (e.g., firefighters, paramedics, emergency medical technicians, law enforcement officers), and military combat personnel can be exposed to HCV through accidental exposure to blood through accidental needlesticks or blood spatter to the eyes or open wounds.
Universal precautions to protect against such accidental exposures significantly reduce the risk of exposure to HCV.
Recreational exposure to blood
Contact sports and other activities, such as "slam dancing" that may result in accidental blood-to-blood exposure are potential sources of exposure to HCV.
Sexual exposure
Sexual transmission of HCV is considered to be rare. Studies show the risk of sexual transmission in heterosexual, monogamous relationships is extremely rare or even null.
The CDC does not recommend the use of condoms between long-term monogamous discordant couples (where one partner is positive and the other is negative).
However, because of the high prevalence of hepatitis C, this small risk may translate into a non-trivial number of cases transmitted by sexual routes.
Vaginal penetrative sex is believed to have a lower risk of transmission than sexual practices that involve higher levels of trauma to anogenital mucosa (anal penetrative sex, fisting, use of sex toys).
Body piercings and tattoos
Tattooing dyes, ink pots, stylets and piercing implements can transmit HCV-infected blood from one person to another if proper sterilization techniques are not followed.
Tattoos or piercings performed before the mid 1980s, "underground," or non-professionally are of particular concern since sterile techniques in such settings may have been or be insufficient to prevent disease.
Despite these risks, it is rare for tattoos to be directly associated with HCV infection and the U.S. Centers for Disease Control and Prevention's position on this subject states that, "no data exist in the United States indicating that persons with exposures to tattooing alone are at increased risk for HCV infection.
Shared personal care items
Personal care items such as razors, toothbrushes, cuticle scissors, and other manicuring or pedicuring equipment can easily be contaminated with blood.
Sharing such items can potentially lead to exposure to HCV.
Appropriate caution should be taken regarding any medical condition which results in bleeding such as canker sores, cold sores, and immediately after flossing.
HCV is not spread through casual contact such as hugging, kissing, or sharing eating or cooking utensils.

Vertical transmission

Vertical transmission refers to the transmission of a communicable disease from an infected mother to her child during the birth process.
Mother-to-child transmission of hepatitis C has been well described, but occurs relatively infrequently.
Transmission occurs only among women who are HCV RNA positive at the time of delivery; the risk of transmission in this setting is approximately 6 out of 100.
Among women who are both HCV and HIV positive at the time of delivery, the risk of transmitting HCV is increased to approximately 25 out of 100.
The risk of vertical transmission of HCV does not appear to be associated with method of delivery or breastfeeding.

Diagnosis

The diagnosis of "hepatitis C" is rarely made during the acute phase of the disease because the majority of people infected experience no symptoms during this phase of the disease.
Those who do experience acute phase symptoms are rarely ill enough to seek medical attention.
The diagnosis of chronic phase hepatitis C is also challenging due to the absence or lack of specificity of symptoms until advanced liver disease develops, which may not occur until decades into the disease.
Chronic hepatitis C may be suspected on the basis of the medical history (particularly if there is any history of IV drug abuse or inhaled substance usage such as cocaine), a history of piercings or tattoos, unexplained symptoms, or abnormal liver enzymes or liver function tests found during routine blood testing.
Occasionally, hepatitis C is diagnosed as a result of targeted screening such as blood donation (blood donors are screened for numerous blood-borne diseases including hepatitis C) or contact tracing.
Hepatitis C testing begins with serological blood tests used to detect antibodies to HCV. Anti-HCV antibodies can be detected in 80% of patients within 15 weeks after exposure, in >90% within 5 months after exposure, and in >97% by 6 months after exposure. Overall, HCV antibody tests have a strong positive predictive value for exposure to the hepatitis C virus, but may miss patients who have not yet developed antibodies (seroconversion), or have an insufficient level of antibodies to detect.
Rarely, people infected with HCV never develop antibodies to the virus and therefore, never test positive using HCV antibody screening.
Because of this possibility, RNA testing (see nucleic acid testing methods below) should be considered when antibody testing is negative but suspicion of hepatitis C is high (e.g. because of elevated transaminases in someone with risk factors for hepatitis C).
Anti-HCV antibodies indicate exposure to the virus, but cannot determine if ongoing infection is present.
All persons with positive anti-HCV antibody tests must undergo additional testing for the presence of the hepatitis C virus itself to determine whether current infection is present.
The presence of the virus is tested for using molecular nucleic acid testing methods such as polymerase chain reaction (PCR), transcription mediated amplification (TMA), or branched DNA (b-DNA). All HCV nucleic acid molecular tests have the capacity to detect not only whether the virus is present, but also to measure the amount of virus present in the blood (the HCV viral load).
The HCV viral load is an important factor in determining the probability of response to interferon-based therapy, but does not indicate disease severity nor the likelihood of disease progression.
In people with confirmed HCV infection, genotype testing is generally recommended. HCV genotype testing is used to determine the required length and potential response to interferon-based therapy.

Treatment

There is a very small chance of clearing the virus spontaneously in chronic HCV carriers (0.5 to 0.74% per year), however, the majority of patients with chronic hepatitis C will not clear it without treatment.
Current treatment is a combination of pegylated interferon alpha (brand names Pegasys and PEG-Intron) and the antiviral drug ribavirin for a period of 24 or 48 weeks, depending on genotype.
Indications for treatment include patients with proven hepatitis C virus infection and persistent abnormal liver function tests. Sustained cure rates (sustained viral response) of 75% or better occur in people with genotypes HCV 2 and 3 in 24 weeks of treatment,[21] about 50% in those with genotype 1 with 48 weeks of treatment and 65% for those with genotype 4 in 48 weeks of treatment.
About 80% of hepatitis C patients in the United States have genotype 1. Genotype 4 is more common in the Middle East and Africa. Should treatment with pegylated interferon + ribavirin not return a 2-log viral reduction or complete clearance of RNA (termed early virological response) after 12 weeks for genotype 1, the chance of treatment success is less than 1%. Early virological response is typically not tested for in non-genotype 1 patients, as the chances of attaining it are greater than 90%.
The mechanism of action is not entirely clear, because even patients who appear to have had a sustained virological response still have actively replicating virus in their liver and peripheral blood mononuclear cells.
The evidence for treatment in genotype 6 disease is currently sparse, and the evidence that exists is for 48 weeks of treatment at the same doses as are used for genotype 1 disease. Physicians considering shorter durations of treatment (e.g., 24 weeks) should do so within the context of a clinical trial.
Treatment during the acute infection phase has much higher success rates (greater than 90%) with a shorter duration of treatment; however, this must be balanced against the 15-40% chance of spontaneous clearance without treatment (see Acute Hepatitis C section above).
Those with low initial viral loads respond much better to treatment than those with higher viral loads (greater than 400,000 IU/mL).
Current combination therapy is usually supervised by physicians in the fields of gastroenterology, hepatology or infectious disease.
The treatment may be physically demanding, particularly for those with a prior history of drug or alcohol abuse.
It can qualify for temporary disability in some cases.
A substantial proportion of patients will experience a panoply of side effects ranging from a 'flu-like' syndrome (the most common, experienced for a few days after the weekly injection of interferon) to severe adverse events including anemia, cardiovascular events and psychiatric problems such as suicide or suicidal ideation.
The latter are exacerbated by the general physiological stress experienced by the patient.
Current guidelines strongly recommend that hepatitis C patients be vaccinated for hepatitis A and B if they have not yet been exposed to these viruses, as infection with a second virus could worsen their liver disease.
Alcoholic beverage consumption accelerates HCV associated fibrosis and cirrhosis, and makes liver cancer more likely; insulin resistance and metabolic syndrome may similarly worsen the hepatic prognosis.
There is also evidence that smoking increases the fibrosis (scarring) rate.

During pregnancy and breastfeeding

If a woman who is pregnant has risk factors for hepatitis C, she should be tested for antibodies against HCV. About 4% infants born to HCV infected women become infected.
There is no treatment that can prevent this from happening.
There is a high chance of the baby ridding the HCV in the first 12 months.
In a mother that also has HIV, the rate of transmission can be as high as 19%.
There are currently no data to determine whether antiviral therapy reduces perinatal transmission.
Ribavirin and interferons are contraindicated during pregnancy.
However, avoiding fetal scalp monitoring and prolonged labor after rupture of membranes may reduce the risk of transmission to the infant.
HCV antibodies from the mother may persist in infants until 15 months of age.
If an early diagnosis is desired, testing for HCV RNA can be performed between the ages of 2 and 6 months, with a repeat test done independent of the first test result.
If a later diagnosis is preferred, an anti-HCV test can performed after 15 months of age.
Most infants infected with HCV at the time of birth have no symptoms and do well during childhood.
There is no evidence that breast-feeding spreads HCV. To be cautious, an infected mother should avoid breastfeeding if her nipples are cracked and bleeding.

Alternative therapies

Several alternative therapies aim to maintain liver functionality, rather than treat the virus itself, thereby slowing the course of the disease to retain quality of life.
As an example, extract of Silybum marianum and Sho-saiko-to are sold for their HCV related effects; the first is said to provide some generic help to hepatic functions, and the second claims to aid in liver health and provide some antiviral effects.
There has never been any verifiable histologic or virologic benefit demonstrated with any of the alternative therapies.

Experimental treatments

The drug viramidine, which is a prodrug of ribavirin that has better targeting for the liver, and therefore may be more effective against hepatitis C for a given tolerated dose, is in phase III experimental trials against hepatitis C.
It will be used in conjunction with interferons, in the same manner as ribavirin.
However, this drug is not expected to be active against ribavirin-resistant strains, and the use of the drug against infections which have already failed ribavirin/interferon treatment, is unproven.
There are new drugs under development like the protease inhibitors (including VX 950) and polymerase inhibitors (such as NM 283), but development of some of these is still in the early phase. VX 950, also known as Telaprevir is currently in Phase 3 Trials.
One protease inhibitor, BILN 2061, had to be discontinued due to safety problems early in the clinical testing.
Some more modern new drugs that provide some support in treating HCV are Albuferon, Zadaxin, and DAPY.
Antisense phosphorothioate oligos have been targeted to hepatitis C.
Antisense Morpholino oligos have shown promise in preclinical studies
however, they were found to cause a limited viral load reduction.
Immunoglobulins against the hepatitis C virus exist and newer types are under development. Thus far, their roles have been unclear as they have not been shown to help in clearing chronic infection or in the prevention of infection with acute exposures (e.g. needlesticks).
They do have a limited role in transplant patients.
In addition to the standard treatment with interferon and ribavirin, some studies have shown higher success rates when the antiviral drug amantadine (Symmetrel) is added to the regimen.
Sometimes called "triple therapy", it involves the addition of 100 mg of amantadine twice a day.
Studies indicate that this may be especially helpful for "nonresponders" - patients who have not been successful in previous treatments using interferon and ribavirin only.
Currently, amantadine is not approved for treatment of Hepatitis C, and studies are ongoing to determine when it is most likely to benefit the patient.

Epidemiology

Hepatitis C infects nearly 200 million people worldwide and 4 million in the United States.
There are about 35,000 to 185,000 new cases a year in the United States.
It is currently a leading cause of cirrhosis, a common cause of hepatocellular carcinoma, and as a result of these conditions it is the leading reason for liver transplantation in the United States.
Co-infection with HIV is common and rates among HIV positive populations are higher. 10,000-20,000 deaths a year in the United States are from HCV; expectations are that this mortality rate will increase, as those who were infected by transfusion before HCV testing become apparent.
A survey conducted in California showed prevalence of up to 34% among prison inmates; 82% of subjects diagnosed with hepatitis C have previously been in jail, and transmission while in prison is well described.
Prevalence is higher in some countries in Africa and Asia.
Egypt has the highest seroprevalence for HCV, up to 20% in some areas.
There is a hypothesis that the high prevalence is linked to a now-discontinued mass-treatment campaign for schistosomiasis, which is endemic in that country.
Regardless of how the epidemic started, a high rate of HCV transmission continues in Egypt, both iatrogenically and within the community and household.

Co-infection with HIV

Approximately 350,000, or 35% of patients in the USA infected with HIV are also infected with the hepatitis C virus, mainly because both viruses are blood-borne and present in similar populations.
In other countries co-infection is less common, and this is possibly related to differing drug policies.[citation needed] HCV is the leading cause of chronic liver disease in the USA.
It has been demonstrated in clinical studies that HIV infection causes a more rapid progression of chronic hepatitis C to cirrhosis and liver failure.
This is not to say treatment is not an option for those living with co-infection.

Prevention

The following guidelines will prevent infection with the hepatitis C virus, which is spread by blood:
* Avoid sharing drug needles or any other drug paraphernalia including works for injection or bills or straws
* Avoid unsanitary tattoo methods
* Avoid unsanitary body piercing methods
* Avoid unsanitary acupuncture
* Avoid needlestick injury
* Avoid sharing personal items such as toothbrushes, razors, and nail clippers.
* Use latex condoms correctly and every time you have sex if not in a long-term monogamous relationship
Proponents of harm reduction believe that strategies such as the provision of new needles and syringes, and education about safer drug injection procedures, greatly decreases the risk of hepatitis C spreading between injecting drug users.
No vaccine protects against contracting hepatitis C, or helps to treat it. Vaccines are under development and some have shown encouraging results.

History

In the mid 1970s, Harvey J. Alter, Chief of the Infectious Disease Section in the Department of Transfusion Medicine at the National Institutes of Health, and his research team demonstrated that most post-transfusion hepatitis cases were not due to hepatitis A or B viruses. Despite this discovery, international research efforts to identify the virus, initially called non-A, non-B hepatitis (NANBH), failed for the next decade.
In 1987, Michael Houghton, Qui-Lim Choo, and George Kuo at Chiron Corporation, collaborating with Dr. D.W. Bradley from CDC, utilized a novel molecular cloning approach to identify the unknown organism.
In 1988, the virus was confirmed by Alter by verifying its presence in a panel of NANBH specimens. In April of 1989, the discovery of the virus, re-named hepatitis C virus (HCV), was published in two articles in the journal Science.
Chiron filed for several patents on the virus and its diagnosis.
A competing patent application by the CDC was dropped in 1990 after Chiron paid $1.9 million to the CDC and $337,500 to Bradley. In 1994 Bradley sued Chiron, seeking to invalidate the patent, have himself included as a co-inventor, and receive damages and royalty income. He dropped the suit in 1998 after losing before an appeals court.
In 2000, Drs. Alter and Houghton were honored with the Lasker Award for Clinical Medical Research for "pioneering work leading to the discovery of the virus that causes hepatitis C and the development of screening methods that reduced the risk of blood transfusion-associated hepatitis in the U.S. from 30% in 1970 to virtually zero in 2000.
In 2004 Chiron held 100 patents in 20 countries related to hepatitis C and had successfully sued many companies for infringement.
Scientists and competitors have complained that the company hinders the fight against hepatitis C by demanding too much money for its technology.

HEPATITIS B

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Hepatitis B is a disease caused by HBV hepatitis B virus which infects the liver of hominoidae, including humans, and causes an inflammation called hepatitis.
Originally known as "serum hepatitis", the disease has caused epidemics in parts of Asia and Africa, and it is endemic in China.
About a third of the world's population, more than 2 billion people, have been infected with the hepatitis B virus.
This includes 350 million chronic carriers of the virus.
Transmission of hepatitis B virus results from exposure to infectious blood or body fluids containing blood.
The acute illness causes liver inflammation, vomiting, jaundice and—rarely—death. Chronic hepatitis B may eventually cause liver cirrhosis and liver cancer—a fatal disease with very poor response to current chemotherapy.
The infection is preventable by vaccination.
Hepatitis B virus is an hepadnavirus—hepa from hepatotrophic and dna because it is a DNA virus—and it has a circular genome composed of partially double-stranded DNA.
The viruses replicate through an RNA intermediate form by reverse transcription, and in this respect they are similar to retroviruses.
Although replication takes place in the liver, the virus spreads to the blood where virus-specific proteins and their corresponding antibodies are found in infected people.
Blood tests for these proteins and antibodies are used to diagnose the infection.

Virology

Hepatitis B virus (HBV) is a member of the Hepadnavirus family.
The virus particle, (virion) consists of an outer lipid envelope and an icosahedral nucleocapsid core composed of protein.
The nucleocapsid encloses the viral DNA and a DNA polymerase that has reverse transcriptase activity.
The outer envelope contains embedded proteins which are involved in viral binding of, and entry into, susceptible cells.
The virus is one of the smallest enveloped animal viruses with a virion diameter of 42nm, but pleomorphic forms exist, including filamentous and spherical bodies lacking a core.
These particles are not infectious and are composed of the lipid and protein that forms part of the surface of the virion, which is called the surface antigen (HBsAg), and is produced in excess during the life cycle of the virus.

Genome

The genome of HBV is made of circular DNA, but it is unusual because the DNA is not fully double-stranded. One end of the full length strand is linked to the viral DNA polymerase.
The genome is 3020-3320 nucleotides long (for the full length strand) and 1700-2800 nucleotides long (for the short length strand).
The negative-sense, (non-coding), is complementary to the viral mRNA.
The viral DNA is found in the nucleus soon after infection of the cell. The partially double-stranded DNA is rendered fully double-stranded by completion of the (+) sense strand and removal of a protein molecule from the (-) sense strand and a short sequence of RNA from the (+) sense strand.
Non-coding bases are removed from the ends of the (-)sense strand and the ends are rejoined.
There are four known genes encoded by the genome called C, X, P, and S.
The core protein is coded for by gene C (HBcAg), and its start codon is preceded by an upstream in-frame AUG start codon from which the pre-core protein is produced.
HBeAg is produced by proteolytic processing of the pre-core protein.
The DNA polymerase is encoded by gene P. Gene S is the gene that codes for the surface antigen (HBsAg).
The HBsAg gene is one long open reading frame but contains three in frame "start" (ATG) codons that divide the gene into three sections, pre-S1, pre-S2, and S. Because of the multiple start codons, polypeptides of three different sizes called large, middle, and small (pre-S1 + pre-S2 + S, pre-S2 + S, or S) are produced.
The function of the protein coded for by gene X is not fully understood.[13]

Replication

The life cycle of Hepatitis B virus is complex. Hepatitis B is one of a few known non-retroviral viruses which use reverse transcription as a part of its replication process.
The virus gains entry into the cell by binding to an unknown receptor on the surface of the cell and enters it by endocytosis.
Because the virus multiplies via RNA made by a host enzyme, the viral genomic DNA has to be transferred to the cell nucleus by host proteins called chaperones.
The partially double stranded viral DNA is then made fully double stranded and transformed into covalently closed circular DNA (cccDNA) that serves as a template for transcription of four viral mRNAs. The largest mRNA, (which is longer than the viral genome), is used to make the new copies of the genome and to make the capsid core protein and the viral DNA polymerase.
These four viral transcripts undergo additional processing and go on to form progeny virions which are released from the cell or returned to the nucleus and re-cycled to produce even more copies.
The long mRNA is then transported back to the cytoplasm where the virion P protein synthesizes DNA via its reverse transcriptase activity.

Serotypes

The virus is divided into four major serotypes (adr, adw, ayr, ayw) based on antigenic epitopes presented on its envelope proteins, and into eight genotypes (A-H) according to overall nucleotide sequence variation of the genome.
The genotypes have a distinct geographical distribution and are used in tracing the evolution and transmission of the virus.
Differences between genotypes affect the disease severity, course and likelihood of complications, and response to treatment and possibly vaccination.

Pathogenesis

Cirrhosis of the liver and liver cancer may ensue from Hepatitis B.
The hepatitis B virus primarily interferes with the functions of the liver by replicating in liver cells, known as hepatocytes.
The receptor is not yet known, though there is evidence that the receptor in the closely related duck hepatitis B virus is carboxypeptidase D.
HBV virions (DANE particle) bind to the host cell via the preS domain of the viral surface antigen and are subsequently internalized by endocytosis.
PreS and IgA receptors are accused of this interaction.
HBV-preS specific receptors are primarily expressed on hepatocytes; however, viral DNA and proteins have also been detected in extrahepatic sites, suggesting that cellular receptors for HBV may also exist on extrahepatic cells.
During HBV infection, the host immune response causes both hepatocellular damage and viral clearance.
Although the innate immune response does not play a significant role in these processes, the adaptive immune response, particularly virus-specific cytotoxic T lymphocytes (CTLs), contributes to most of the liver injury associated with HBV infection.
By killing infected cells and by producing antiviral cytokines capable of purging HBV from viable hepatocytes, CTLs eliminate the virus.[19] Although liver damage is initiated and mediated by the CTLs, antigen-nonspecific inflammatory cells can worsen CTL-induced immunopathology, and platelets activated at the site of infection may facilitate the accumulation of CTLs in the liver.

Epidemiology

The primary method of transmission reflects the prevalence of chronic HBV infection in a given area.
In low prevalence areas such as the continental United States and Western Europe, where less than 2% of the population is chronically infected, injection drug abuse and unprotected sex are the primary methods, although other factors may be important.
In moderate prevalence areas, which include Eastern Europe, Russia, and Japan, where 2-7% of the population is chronically infected, the disease is predominantly spread among children.
In high prevalence areas such as China and South East Asia, transmission during childbirth is most common, although in other areas of high endemicity such as Africa, transmission during childhood is a significant factor.
The prevalence of chronic HBV infection in areas of high endemicity is at least 8%.

Transmission

Transmission of hepatitis B virus results from exposure to infectious blood or body fluids containing blood.
Possible forms of transmission include (but are not limited to) unprotected sexual contact, blood transfusions, re-use of contaminated needles & syringes, and vertical transmission from mother to child during childbirth.
Without intervention, a mother who is positive for HBsAg confers a 20% risk of passing the infection to her offspring at the time of birth. This risk is as high as 90% if the mother is also positive for HBeAg.
HBV can be transmitted between family members within households, possibly by contact of nonintact skin or mucous membrane with secretions or saliva containing HBV.
However, at least 30% of reported hepatitis B among adults cannot be associated with an identifiable risk factor.

Medical aspects

Several vaccines have been developed for the prevention of hepatitis B virus infection.
These rely on the use of one of the viral envelope proteins (hepatitis B surface antigen or HBsAg).
The vaccine was originally prepared from plasma obtained from patients who had long-standing hepatitis B virus infection.
However, currently, these are more often made using recombinant DNA technology, though plasma-derived vaccines continue to be used; the two types of vaccines are equally effective and safe.
Following vaccination Hepatitis B Surface antigen may be detected in serum for several days; this is known as vaccine antigenaemia.
Vaccine is generally administered in either a two, three, or four dose schedules; and can be received by infants to adults. It provides protection for 85-90% of individuals, and lasts for 23 years.
Unlike Hepatitis A, Hepatitis B does not generally spread through water and food.
Instead, it is transmitted through body fluids, from which prevention is taken to avoid: unprotected sexual contact, blood transfusions, re-use of contaminated needles and syringes, and vertical transmission during child birth.
Infants may be vaccinated at birth.

Symptoms

Acute infection with hepatitis B virus is associated with acute viral hepatitis - an illness that begins with general ill-health, loss of appetite, nausea, vomiting, body aches, mild fever, dark urine, and then progresses to development of jaundice.
It has been noted that itchy skin has been an indication as a possible symptom of all hepatitis virus types.
The illness lasts for a few weeks and then gradually improves in most affected people.
A few patients may have more severe liver disease (fulminant hepatic failure), and may die as a result of it.
The infection may be entirely asymptomatic and may go unrecognized.
Chronic infection with Hepatitis B virus may be either asymptomatic or may be associated with a chronic inflammation of the liver (chronic hepatitis), leading to cirrhosis over a period of several years.
This type of infection dramatically increases the incidence of hepatocellular carcinoma (liver cancer). Chronic carriers are encouraged to avoid consuming alcohol as it increases their risk for cirrhosis and liver cancer.
Hepatitis B virus has been linked to the development of Membranous glomerulonephritis (MGN).

Diagnosis

The hepatitis B surface antigen (HBsAg) is most frequently used to screen for the presence of this infection.
It is the first detectable viral antigen to appear during infection.
However, early in an infection, this antigen may not be present and it may be undetectable later in the infection as it is being cleared by the host.
The infectious virion contains an inner "core particle" enclosing viral genome.
The icosahedral core particle is made of 180 or 240 copies of core protein, alternatively known as hepatitis B core antigen, or HBcAg.
During this 'window' in which the host remains infected but is successfully clearing the virus, IgM antibodies to the hepatitis B core antigen (anti-HBc IgM) may be the only serological evidence of disease.
Shortly after the appearance of the HBsAg, another antigen named as the hepatitis B e antigen (HBeAg) will appear.
Traditionally, the presence of HBeAg in a host's serum is associated with much higher rates of viral replication and enhanced infectivity; however, variants of the hepatitis B virus do not produce the 'e' antigen, so this rule does not always hold true.
During the natural course of an infection, the HBeAg may be cleared, and antibodies to the 'e' antigen (anti-HBe) will arise immediately afterwards.
This conversion is usually associated with a dramatic decline in viral replication.
If the host is able to clear the infection, eventually the HBsAg will become undetectable and will be followed by IgG antibodies to the hepatitis B surface antigen and core antigen, (anti-HBs and anti HBc IgG). A person negative for HBsAg but positive for anti-HBs has either cleared an infection or has been vaccinated previously.
Individuals who remain HBsAg positive for at least six months are considered to be hepatitis B carriers.
Carriers of the virus may have chronic hepatitis B, which would be reflected by elevated serum alanine aminotransferase levels and inflammation of the liver, as revealed by biopsy.
Carriers who have seroconverted to HBeAg negative status, particularly those who acquired the infection as adults, have very little viral multiplication and hence may be at little risk of long-term complications or of transmitting infection to others.
More recently, PCR tests have been developed to detect and measure the amount of viral nucleic acid in clinical specimens.
These tests are called viral loads and are used to assess a person's infection status and to monitor treatment.

Prognosis

Hepatitis B virus infection may either be acute (self-limiting) or chronic (long-standing).
Persons with self-limiting infection clear the infection spontaneously within weeks to months.
Children are less likely than adults to clear the infection.
More than 95% of people who become infected as adults or older children will stage a full recovery and develop protective immunity to the virus.
However, only 5% of newborns that acquire the infection from their mother at birth will clear the infection. This population has a 40% lifetime risk of death from cirrhosis or hepatocellular carcinoma.
Of those infected between the age of one to six, 70% will clear the infection.
Hepatitis D infection can only occur with a concomitant infection with Hepatitis B virus because the Hepatitis D virus uses the Hepatitis B virus surface antigen to form a capsid.
Co-infection with hepatitis D increases the risk of liver cirrhosis and liver cancer.
Polyarteritis nodosa is more common in people with hepatitis B infection.

Treatment

Acute hepatitis B infection does not usually require treatment because most adults clear the infection spontaneously.
Early antiviral treatment may only be required in fewer than 1% of patients, whose infection takes a very aggressive course ("fulminant hepatitis") or who are immunocompromised.
On the other hand, treatment of chronic infection may be necessary to reduce the risk of cirrhosis and liver cancer.
Chronically infected individuals with persistently elevated serum alanine aminotransferase, a marker of liver damage, and HBV DNA levels are candidates for therapy.
Although none of the available drugs can clear the infection, they can stop the virus from replicating, and minimize liver damage such as cirrhosis and liver cancer.
Currently, there are seven medications licensed for treatment of hepatitis B infection in the United States.
These include antiviral drugs lamivudine (Epivir), adefovir (Hepsera), tenofovir (Viread), telbivudine (Tyzeka) and entecavir (Baraclude) and the two immune system modulators interferon alpha-2a and pegylated interferon alfa-2a (Pegasys). The use of interferon, which requires injections daily or thrice weekly, has been supplanted by long-acting pegylated interferon, which is injected only once weekly.
However, some individuals are much more likely to respond than others and this might be because of the genotype of the infecting virus or the patient's heredity.
The treatment works by reducing the viral load, (the amount of virus particles as measured in the blood), which in turn reduces viral replication in the liver.
Infants born to mothers known to carry hepatitis B can be treated with antibodies to the hepatitis B virus (hepatitis B immune globulin or HBIg).
When given with the vaccine within twelve hours of birth, the risk of acquiring hepatitis B is reduced 95%. This treatment allows a mother to safely breastfeed her child.

Reactivation

Hepatitis B virus DNA persists in the body after infection and in some people the disease recurs.
Although rare, reactivation is seen most often in people with impaired immunity.
Hepatitis B goes through cycles of replication and non-replication.
Approximately 50% of patients experience acute reactivation.
Male patients with baseline ALT of 200 UL/L are three times more likely to develop a reactivation than patients with lower levels.
Patients who undergo chemotherapy are at risk for HBV reactivation.
The current view are that immunosuppressive drugs favor increased HBV replication while inhibiting cytotoxic T cell function in the liver.

History

The earliest record of an epidemic caused by Hepatitis B virus was made by Lurman in 1885.
An outbreak of smallpox occurred in Bremen in 1883 and 1,289 shipyard employees were vaccinated with lymph from other people. After several weeks, and up to eight months later, 191 of the vaccinated workers became ill with jaundice and were diagnosed as suffering from serum hepatitis.
Other employees who had been inoculated with different batches of lymph remained healthy.
Lurman's paper, now regarded as a classical example of an epidemiological study, proved that contaminated lymph was the source of the outbreak.
Later, numerous similar outbreaks were reported following the introduction, in 1909, of hypodermic needles that were used, and more importantly reused, for administering Salvarsan for the treatment of syphilis.
The virus was not discovered until 1965 when Baruch Blumberg, then working at the National Institutes of Health (NIH), discovered the Australia antigen (later known to be Hepatitis B surface antigen, or HBsAg) in the blood of Australian aboriginal people.
Although a virus had been suspected since the research published by MacCallum in 1947, D.S. Dane and others discovered the virus particle in 1970 by electron microscopy.
By the early 1980s the genome of the virus had been sequenced, and the first vaccines were being tested.
Hepatitis C is an infectious disease affecting the liver, caused by the hepatitis C virus (HCV).
The infection is often asymptomatic, but once established, chronic infection can progress to scarring of the liver (fibrosis), and advanced scarring (cirrhosis) which is generally apparent after many years. In some cases, those with cirrhosis will go on to develop liver failure or other complications of cirrhosis, including liver cancer.

HEPATITIS A

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Hepatitis A

Hepatitis A (formerly known as infectious hepatitis) is an acute infectious disease of the liver caused by the hepatitis A virus (HAV)
It is most commonly transmitted by the fecal-oral route via contaminated food or drinking water. Every year, approximately 10 million people worldwide are infected with the virus.
The time between infection and the appearance of the symptoms, (the incubation period), is between two and six weeks and the average incubation period is 28 days.
In developing countries, and in regions with poor hygiene standards, the incidence of infection with this virus is high and the illness is usually contracted in early childhood.
HAV has also been found in samples taken to study ocean water quality.
Hepatitis A infection causes no clinical signs and symptoms in over 90% of these children and since the infection confers lifelong immunity, the disease is of no special significance to the indigenous population. In Europe, the United States and other industrialized countries, on the other hand, the infection is contracted primarily by susceptible young adults, most of whom are infected with the virus during trips to countries with a high incidence of the disease.
Hepatitis A does not have a chronic stage and does not cause permanent liver damage.
Following infection, the immune system makes antibodies against HAV that confer immunity against future infection.
The disease can be prevented by vaccination and hepatitis A vaccine has been proven effective in controlling outbreaks worldwide.

Virology

The Hepatitis virus (HAV) is a Picornavirus; it is non-enveloped and contains a single-stranded RNA packaged in a protein shell. There is only one type of the virus.

Pathogenesis

Following ingestion, HAV enters the bloodstream through the epithelium of the oropharynx or intestine.
The blood carries the virus to its target, the liver, and multiplies within hepatocytes and Kupffer cells (i.e., liver macrophages). There is no apparent virus-mediated cytotoxicity, and liver pathology is likely immune-mediated.
Virions are secreted into the bile and released in stool.
HAV is excreted in large quantities approximately 11 days prior to appearance of symptoms or anti-HAV IgM antibodies in the blood.
The incubation period is 15-50 days, and mortality is less than 0.5%.

Epidemiology

HAV is found in the feces of infected persons and those who are at higher risk include travelers to developing countries where there is a higher incidence rate, and those having sexual contact or drug use with infected persons.
There were 30,000 cases of Hepatitis A reported to the CDC in the U.S. in 1997. The agency estimates that there were as many as 270,000 cases each year from 1980 through 2000.

Transmission

The virus spreads by the fecal-oral route and infections often occur in conditions of poor sanitation and overcrowding.
Hepatitis A can be transmitted by the parenteral route but very rarely by blood and blood products.
Food-borne outbreaks are not uncommon, and ingestion of shellfish cultivated in polluted water is associated with a high risk of infection.
Approximately 40% of all acute viral hepatitis is caused by HAV.
Infected individuals are infectious prior to onset of symptoms, roughly 10 days following infection.
The virus is resistant to detergent, acid (pH 1), solvents (e.g., ether, chloroform), drying, and temperatures up to 60oC. It can survive for months in fresh and salt water.
Common-source (e.g., water, restaurant) outbreaks are typical.
Infection is common in children in developing countries, reaching 100% incidence, but following infection there is life-long immunity.
HAV can be inactivated by: chlorine treatment (drinking water), formalin (0.35%, 37oC, 72 hours), peracetic acid (2%, 4 hours), beta-propiolactone (0.25%, 1 hour), and UV radiation (2 μW/cm2/min).

Cases

The most widespread hepatitis A outbreak in the United States afflicted at least 640 people (killing four) in north-eastern Ohio and south-western Pennsylvania in late 2003.
The outbreak was blamed on tainted green onions at a restaurant in Monaca, Pennsylvania. In 1988, 300,000 people in Shanghai, China were infected with HAV after eating clams from a contaminated river.[14]

Prevention

Hepatitis A can be prevented by vaccination, good hygiene and sanitation.[1][15] Hepatitis A is also one of the main reasons not to surf or go in the ocean after rains in coastal areas that are known to have bad runoff.
The vaccine protects against HAV in more than 95% of cases for 10 years. It contains inactivated Hepatitis A virus providing active immunity against a future infection.
The vaccine was first phased in 1996 for children in high-risk areas, and in 1999 it was spread to areas with elevating levels of infection.
The vaccine is given in two doses in the muscle of the upper arm.
The first dose provides protection two to four weeks after initial vaccination; the second booster dose, given six to twelve months later, provides protection for up to twenty years.

Symptoms

Early symptoms of hepatitis A infection can be mistaken for influenza, but some sufferers, especially children, exhibit no symptoms at all.
Symptoms typically appear 2 to 6 weeks, (the incubation period ), after the initial infection.
Symptoms can return over the following 6-9 months which include:

* Fatigue
* Fever
* Abdominal pain
* Nausea
* Diarrhea
* Appetite loss
* Depression
* Jaundice, a yellowing of the skin or whites of the eyes
* Sharp pains in the right-upper quadrant of the abdomen
* Weight loss
* Itching

Diagnosis

Serum IgG, IgM and ALT following Hepatitis A virus infection
Although HAV is excreted in the feces towards the end of the incubation period, specific diagnosis is made by the detection of HAV-specific IgM antibodies in the blood.
IgM antibody is only present in the blood following an acute hepatitis A infection.
It is detectable from one to two weeks after the initial infection and persists for up to 14 weeks.
The presence of IgG antibody in the blood means that the acute stage of the illness is past and the person is immune to further infection.
IgG antibody to HAV is also found in the blood following vaccination and tests for immunity to the virus are based on the detection of this antibody.
During the acute stage of the infection, the liver enzyme alanine transferase (ALT) is present in the blood at levels much higher than is normal.
The enzyme comes from the liver cells that have been damaged by the virus.
Hepatitis A virus is present in the blood, (viremia), and feces of infected people up to two weeks before clinical illness develops.

Prognosis

The United States Centers for Disease Control and Prevention (CDC) in 1991 reported a low mortality rate for hepatitis A of 4 deaths per 1000 cases for the general population but a higher rate of 17.5 per 1000, in those aged 50 and over.
Death usually occurs when the patient contracts Hepatitis A while already suffering from another form of Hepatitis, such as Hepatitis B or Hepatitis C or AIDS.
Young children who are infected with hepatitis A typically have a milder form of the disease, usually lasting from 1-3 weeks, whereas adults tend to experience a much more severe form of the disease.

Treatment

There is no specific treatment for hepatitis A.
Sufferers are advised to rest, avoid fatty foods and alcohol (these may be poorly tolerated for some additional months during the recovery phase and cause minor relapses), eat a well-balanced diet, and stay hydrated. Approximately 15% of people diagnosed with hepatitis A may experience one or more symptomatic relapse(s) for up to 24 months after contracting this disease.

HEPATITIS

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Hepatitis

Hepatitis (plural hepatitides) implies injury to the liver characterized by the presence of inflammatory cells in the tissue of the organ. The name is from ancient Greek hepar (ἧπαρ), the root being hepat- (ἡπατ-), meaning liver, and suffix -itis, meaning "inflammation" (c. 1727)[1]. The condition can be self-limiting, healing on its own, or can progress to scarring of the liver. Hepatitis is acute when it lasts less than six months and chronic when it persists longer. A group of viruses known as the hepatitis viruses cause most cases of liver damage worldwide. Hepatitis can also be due to toxins (notably alcohol), other infections or from autoimmune process. It may run a subclinical course when the affected person may not feel ill. The patient becomes unwell and symptomatic when the disease impairs liver functions that include, among other things, removal of harmful substances, regulation of blood composition, and production of bile to help digestion.

Causes

Acute

* Viral hepatitis: Hepatitis A through E (more than 95% of viral cause), Herpes simplex, Cytomegalovirus, Epstein-Barr, yellow fever virus, adenoviruses.
* Non viral infection: toxoplasma, Leptospira, Q fever,[2] rocky mountain spotted fever[3]
* Alcohol
* Toxins: Amanita toxin in mushrooms, carbon tetrachloride, asafetida
* Drugs: Paracetamol, amoxycillin, antituberculosis medicines, minocycline and many others (see longer list below).
* Ischemic hepatitis (circulatory insufficiency)
* Pregnancy
* Auto immune conditions, e.g., Systemic Lupus Erythematosus (SLE)
* Metabolic diseases, e.g., Wilson's disease

Chronic

* Viral hepatitis: Hepatitis B with or without hepatitis D, hepatitis C (neither hepatitis A nor hepatitis E causes chronic hepatitis)
* Autoimmune: Autoimmune hepatitis
* Alcohol
* Drugs: methyldopa, nitrofurantoin, isoniazid, ketoconazole
* Non-alcoholic steatohepatitis
* Heredity: Wilson's disease, alpha 1-antitrypsin deficiency
* Primary biliary cirrhosis and primary sclerosing cholangitis occasionally mimic chronic hepatitis[4]

Symptoms

Acute

Clinically, the course of acute hepatitis varies widely from mild symptoms requiring no treatment to fulminant hepatic failure needing liver transplantation. Acute viral hepatitis is more likely to be asymptomatic in younger people. Symptomatic individuals may present after convalescent stage of 7 to 10 days, with the total illness lasting 2 to 6 weeks.[4]

Initial features are of nonspecific flu-like symptoms, common to almost all acute viral infections and may include malaise, muscle and joint aches, fever, nausea or vomiting, diarrhea, and headache. More specific symptoms, which can be present in acute hepatitis from any cause, are: profound loss of appetite, aversion to smoking among smokers, dark urine, yellowing of the eyes and skin (i.e., jaundice) and abdominal discomfort. Physical findings are usually minimal, apart from jaundice (33%) and tender hepatomegaly (10%). There can be occasional lymphadenopathy (5%) or splenomegaly (5%).[5]

Chronic

Majority of patients will remain asymptomatic or mildly symptomatic, abnormal blood tests being the only manifestation. Features may be related to the extent of liver damage or the cause of hepatitis. Many experience return of symptoms related to acute hepatitis. Jaundice can be a late feature and may indicate extensive damage. Other features include abdominal fullness from enlarged liver or spleen, low grade fever and fluid retention (ascites). Extensive damage and scarring of liver (i.e., cirrhosis) leads to weight loss, easy bruising and bleeding tendencies. Acne, abnormal menstruation, lung scarring, inflammation of the thyroid gland and kidneys may be present in women with autoimmune hepatitis.[6]

Findings on clinical examination are usually those of cirrhosis or are related to aetiology.

Types

Viral

Most cases of acute hepatitis are due to viral infections:
* Hepatitis A
* Hepatitis B
* Hepatitis C
* Hepatitis B with D
* Hepatitis E
* Hepatitis F virus (existence unknown)
* Hepatitis G, or GBV-C
* In addition to the hepatitis viruses (please note that the hepatitis viruses are not all related), other viruses can also cause hepatitis, including cytomegalovirus, Epstein-Barr virus, yellow fever, etc.

Other viral infections can cause hepatitis (inflammation of the liver):
* Mumps virus
* Rubella virus
* Cytomegalovirus
* Epstein-Barr virus
* Other herpes viruses

Alcoholic hepatitis

Ethanol, mostly in alcoholic beverages, is a significant cause of hepatitis. Usually alcoholic hepatitis comes after a period of increased alcohol consumption. Alcoholic hepatitis is characterized by a variable constellation of symptoms, which may include feeling unwell, enlargement of the liver, development of fluid in the abdomen ascites, and modest elevation of liver blood tests. Alcoholic hepatitis can vary from mild with only liver test elevation to severe liver inflammation with development of jaundice, prolonged prothrombin time, and liver failure. Severe cases are characterized by either obtundation (dulled consciousness) or the combination of elevated bilirubin levels and prolonged prothrombin time; the mortality rate in both categories is 50% within 30 days of onset.

Alcoholic hepatitis is distinct from cirrhosis caused by long term alcohol consumption. Alcoholic hepatitis can occur in patients with chronic alcoholic liver disease and alcoholic cirrhosis. Alcoholic hepatitis by itself does not lead to cirrhosis, but cirrhosis is more common in patients with long term alcohol consumption. Patients who drink alcohol to excess are also more often than others found to have hepatitis C.[citation needed] The combination of hepatitis C and alcohol consumption accelerates the development of cirrhosis.

Drug induced

A large number of drugs can cause hepatitis:[7]
* Allopurinol
* Amitriptyline (antidepressant)
* Amiodarone (antiarrhythmic)
* Atomoxetine [8]
* Azathioprine[9]
* Halothane (a specific type of anesthetic gas)
* Hormonal contraceptives
* Ibuprofen and indomethacin (NSAIDs)
* Isoniazid (INH), rifampicin, and pyrazinamide (tuberculosis-specific antibiotics)
* Ketoconazole (antifungal)
* Loratadine (antihistamine)
* Methotrexate (immune suppressant)
* Methyldopa (antihypertensive)
* Minocycline (tetracycline antibiotic)
* Nifedipine (antihypertensive)
* Nitrofurantoin (antibiotic)
* Paracetamol (acetaminophen in the United States) can cause hepatitis when taken in an overdose. The severity of liver damage may be limited by prompt administration of acetylcysteine.
* Phenytoin and valproic acid (antiepileptics)
* Troglitazone (antidiabetic, withdrawn in 2000 for causing hepatitis)
* Zidovudine (antiretroviral i.e., against HIV)
* Some herbs and nutritional supplements[10]

The clinical course of drug-induced hepatitis is quite variable, depending on the drug and the patient's tendency to react to the drug. For example, halothane hepatitis can range from mild to fatal as can INH-induced hepatitis. Hormonal contraception can cause structural changes in the liver. Amiodarone hepatitis can be untreatable since the long half life of the drug (up to 60 days) means that there is no effective way to stop exposure to the drug. Statins can cause elevations of liver function blood tests normally without indicating an underlying hepatitis. Lastly, human variability is such that any drug can be a cause of hepatitis.

Toxins

Other Toxins can cause hepatitis:
* Amatoxin-containing mushrooms, including the Death Cap (Amanita phalloides), the Destroying Angel (Amanita ocreata), and some species of Galerina. A portion of a single mushroom can be enough to be lethal (10 mg or less of α-amanitin).
* White phosphorus, an industrial toxin and war chemical.
* Carbon tetrachloride ("tetra", a dry cleaning agent), chloroform, and trichloroethylene, all chlorinated hydrocarbons, cause steatohepatitis (hepatitis with fatty liver).
* Cylindrospermopsin, a toxin from the cyanobacterium Cylindrospermopsis raciborskii and other cyanobacteria.

Metabolic disorders

Some metabolic disorders cause different forms of hepatitis. Hemochromatosis (due to iron accumulation) and Wilson's disease (copper accumulation) can cause liver inflammation and necrosis.

Non-alcoholic steatohepatitis (NASH) is effectively a consequence of metabolic syndrome.

Obstructive

"Obstructive jaundice" is the term used to describe jaundice due to obstruction of the bile duct (by gallstones or external obstruction by cancer). If longstanding, it leads to destruction and inflammation of liver tissue.

Autoimmune

Anomalous presentation of human leukocyte antigen (HLA) class II on the surface of hepatocytes, possibly due to genetic predisposition or acute liver infection; causes a cell-mediated immune response against the body's own liver, resulting in autoimmune hepatitis.

Alpha 1-antitrypsin deficiency

In severe cases of alpha 1-antitrypsin deficiency (A1AD), the accumulated protein in the endoplasmic reticulum causes liver cell damage and inflammation.

Non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the occurrence of fatty liver in people who have no history of alcohol use. It is most commonly associated with obesity (80% of all obese people have fatty liver). It is more common in women. Severe NAFLD leads to inflammation, a state referred to as non-alcoholic steatohepatitis (NASH), which on biopsy of the liver resembles alcoholic hepatitis (with fat droplets and inflammatory cells, but usually no Mallory bodies).

The diagnosis depends on medical history, physical exam, blood tests, radiological imaging and sometimes a liver biopsy. The initial evaluation to identify the presence of fatty infiltration of the liver is medical imaging, including such ultrasound, computed tomography (CT), or magnetic resonance (MRI). However, imaging cannot readily identify inflammation in the liver. Therefore, the differentiation between steatosis and NASH often requires a liver biopsy. It can also be difficult to distinguish NASH from alcoholic hepatitis when the patient has a history of alcohol consumption. Sometimes in such cases a trial of abstinence from alcohol along with follow-up blood tests and a repeated liver biopsy are required.

NASH is becoming recognized as the most important cause of liver disease second only to hepatitis C in numbers of patients going on to cirrhosis.[citation needed]

Ischemic hepatitis

Ischemic hepatitis is caused by decreased circulation to the liver cells. Usually this is due to decreased blood pressure (or shock), leading to the equivalent term "shock liver". Patients with ischemic hepatitis are usually very ill due to the underlying cause of shock. Rarely, ischemic hepatitis can be caused by local problems with the blood vessels that supply oxygen to the liver (such as thrombosis, or clotting of the hepatic artery which partially supplies blood to liver cells). Blood testing of a person with ischemic hepatitis will show very high levels of transaminase enzymes (AST and ALT), which may exceed 1000 U/L. The elevation in these blood tests is usually transient (lasting 7 to 10 days). It is rare that liver function will be affected by ischemic hepatitis.

LIVER FUNCTIONS

2009-07-06T20:11:00.003+03:00

The liver is an organ in living beings, including humans.

It plays a major role in metabolism and has a number of functions in the body including

glycogen storage,

plasma protein synthesis,

drug detoxification.

This organ also is the largest gland in the human body. It produces bile, which is important in digestion.

It performs and regulates a wide variety of high-volume biochemical reactions requiring specialized tissues

NBC4 News - Georgetown's 500th Liver Transplant

2009-06-03T02:08:00.000+03:00

http://

Liver Transplant Update

2009-06-03T01:47:00.001+03:00

http://

Liver Transplantation, Ask Dr. J. Keith Melancon

2009-05-31T20:07:00.001+03:00

Ranking Need for Liver Transplant-Mayo Clinic

2009-05-31T13:41:00.000+03:00

Medical Treatment of Hepatocellular Carcinoma ( HCC )

2009-05-24T20:21:00.000+03:00

Chemotherapy Systemic (entire body) chemotherapy

The most commonly used systemic chemotherapeutic agents are doxorubicin (Adriamycin) and 5-fluorouracil (5 FU). These drugs are used together or in combination with new experimental agents. These drugs are quite toxic and results have been disappointing. A few studies suggest some benefit with tamoxifen (Nolvadex) but just as many studies show no advantage. Octreotide (Sandostatin) given as an injection was shown in one study to slow down the progression of large liver cancer tumors, but so far, no other studies have confirmed this benefit.

Hepatic arterial infusion of chemotherapy

The normal liver gets its blood supply from two sources; the portal vein (about 70%) and the hepatic artery (30%). However, liver cancer gets its blood exclusively from the hepatic artery. Making use of this fact, investigators have delivered chemotherapy agents selectively through the hepatic artery directly to the tumor. The theoretical advantage is that higher concentrations of the agents can be delivered to the tumors without subjecting the patients to the systemic toxicity of the agents.

In reality, however, much of the chemotherapeutic agents does end up in the rest of the body. Therefore, selective intra-arterial chemotherapy can cause the usual systemic (body-wide) side effects. In addition, this treatment can result in some regional side effects, such as inflammation of the gallbladder (cholecystitis), intestinal and stomach ulcers, and inflammation of the pancreas (pancreatitis). Liver cancer patients with advanced cirrhosis may develop liver failure after this treatment. Well then, what is the benefit of intra-arterial chemotherapy? The bottom line is that fewer than 50% of patients will experience a reduction in tumor size.

An interventional radiologist (one who does therapeutic procedures) usually carries out this procedure. The radiologist must work closely with an oncologist (cancer specialist), who determines the amount of chemotherapy that the patient receives at each session. Some patients may undergo repeat sessions at 6 to 12 week intervals. This procedure is done with the help of fluoroscopy (type of x-ray) imaging. A catheter (long, narrow tube) is inserted into the femoral artery in the groin and is threaded into the aorta (the main artery of the body). From the aorta, the catheter is advanced into the hepatic artery. Once the branches of the hepatic artery that feed the liver cancer are identified, the chemotherapy is infused. The whole procedure takes one to two hours, and then the catheter is removed.

The patient generally stays in the hospital overnight for observation. A sandbag is placed over the groin to compress the area where the catheter was inserted into the femoral artery. The nurses periodically check for signs of bleeding from the femoral artery puncture. They also check for the pulse in the foot on the side of the catheter insertion to be sure that the femoral artery is not blocked as a result of the procedure. (Blockage would be signaled by the absence of a pulse.)

Generally, the liver tests increase (get worse) during the two to three days after the procedure. This worsening of the liver tests is actually due to death of the tumor (and some non-tumor) cells. The patient may experience some post-procedure abdominal pain and low-grade fever. However, severe abdominal pain and vomiting suggest that a more serious complication has developed. Imaging studies of the liver are repeated in six to 12 weeks to assess the size of the tumor in response to the treatment. For more, please read the Chemotherapy article.

Chemoembolization (trans-arterial chemoembolization or TACE)

This technique takes advantage of the fact that liver cancer is a very vascular (contains many blood vessels) tumor and gets its blood supply exclusively from the branches of the hepatic artery. This procedure is similar to intra-arterial infusion of chemotherapy. But in TACE, there is the additional step of blocking (embolizing) the small blood vessels with different types of compounds, such as gelfoam or even small metal coils. Thus, TACE has the advantages of exposing the tumor to high concentrations of chemotherapy and confining the agents locally since they are not carried away by the blood stream. At the same time, this technique deprives the tumor of its needed blood supply, which can result in the damage or death of the tumor cells.

The type and frequency of complications of TACE and intra-arterial chemotherapy are similar. The potential disadvantage of TACE is that blocking the feeding vessels to the tumor(s) may make future attempts at intra-arterial infusions impossible. Moreover, so far, there are no head-to-head studies directly comparing the effectiveness of intra-arterial infusion versus chemoembolization. In Japan, the chemotherapeutic agents are mixed with lipiodol. The idea is that since the tumor cells preferentially take up lipiodol, they would likewise take up the chemotherapy. This Japanese technique has not yet been validated in head-to-head comparisons with conventional TACE.

What are the benefits of TACE? In one large study involving several institutions in Italy, chemoembolization did not seem to be beneficial. Patients who did not undergo TACE lived as long as patients who received TACE, even though the tumors were more likely to shrink in size in patients who were treated. Does this mean that TACE or intra-arterial chemotherapy does not work? Maybe, maybe not.

Studies in Japan have shown that TACE can downstage liver cancer. In other words, the tumors shrank enough to lower (improve) the stage of the cancer. From the practical point of view, shrinking the tumor creates the option for surgery in some of these patients. Otherwise, these patients had tumors that were not operable (eligible for operation) because of the initial large size of their tumors. More importantly, these same studies showed an improvement in survival in patients whose tumors became considerably smaller. In the U.S., trials are underway to see whether doing TACE before liver transplantation increases patient survival as compared to liver transplantation without TACE.

It is safe to say that TACE or intra-arterial chemoinfusion are palliative treatment options for liver cancer. This means that these procedures can provide relief or make the disease less severe. However, they are not curative (do not result in a cure). Fewer than 50% of patients will have some shrinkage in tumor size. Further, they can be used only in patients with relatively preserved liver function. The reason for this is that these procedures, as mentioned previously, can lead to liver failure in individuals with poor liver function.

Ablation techniques

Radiofrequency ablation (RFA) therapy

In the U.S., RFA therapy has become the ablation (tissue destruction) therapy of choice among surgeons. The surgeon can perform this procedure laparoscopically (through small holes in the abdomen) or during open exploration of the abdomen. In some instances, the procedure can be done without opening the abdomen by just using ultrasound for visual guidance.

In RFA, heat is generated locally by a high frequency, alternating current that flows from the electrodes. A probe is inserted into the center of the tumor and the non-insulated electrodes, which are shaped like prongs, are projected into the tumor. The local heat that is generated melts the tissue (coagulative necrosis) that is adjacent to the probe. The probe is left in place for about 10 to 15 minutes. The whole procedure is monitored visually by ultrasound scanning. The ideal size of an liver cancer tumor for RFA is less than 3 cm. Larger tumors may require more than one session. This treatment should be viewed as palliative (providing some relief), not curative.

Percutaneous ethanol (alcohol) injection

In this technique, pure alcohol is injected into the tumor through a very thin needle with the help of ultrasound or CT visual guidance. Alcohol induces tumor destruction by drawing water out of tumor cells (dehydrating them) and thereby altering (denaturing) the structure of cellular proteins. It may take up to five or six sessions of injections to completely destroy the cancer. The ideal patient for alcohol injection has fewer than three liver cancer tumors, each of which is:

* well defined (distinct margins)
* less than 3 cm in diameter
* surrounded by a shell consisting of scar tissue (fibrous encapsulation)
* not near the surface of the liver

Additionally, patients with liver cancer undergoing alcohol injection should have no signs of chronic liver failure, such as ascites or jaundice. (Patients with liver failure would not be able to tolerate the alcohol injections.)

The most common side effect of alcohol injection is leakage of alcohol onto the surface of the liver and into the abdominal cavity, thereby causing pain and fever. It is important that the location of the tumor relative to the adjacent blood vessels and bile ducts is clearly identified. The reason for needing to locate these structures is to avoid injuring them during the procedure and causing bleeding, bile duct inflammation, or bile leakage.

Proton beam therapy

This technique is able to deliver high doses of radiation to a defined local area. Proton beam therapy is used in the treatment of other solid tumors as well. There are not much data yet regarding the efficacy of this treatment in liver cancer. The ideal patient is one with only asmall(<5 style="font-size:130%;">Surgery

Surgical options are limited to individuals whose tumors are less than 5 cm and confined to the liver, with no invasion of the blood vessels.

Diagnosis of Liver Cancer

2009-05-24T20:19:00.000+03:00

Blood tests

Liver cancer is not diagnosed by routine blood tests, including a standard panel of liver tests. This is why the diagnosis of liver cancer depends so much on the vigilance of the physician screening with a tumor marker (alpha-fetoprotein) in the blood and radiological imaging studies. Since most patients with liver cancer have associated liver disease (cirrhosis), their liver blood tests may not be normal to begin with. If these blood tests become abnormal or worsen due to liver cancer, this usually signifies extensive cancerous involvement of the liver. At that time, any medical or surgical treatment would be too late.
Sometimes, however, other abnormal blood tests can indicate the presence of liver cancer. Remember that each cell type in the body contains the full complement of genetic information. What differentiates one cell type from another is the particular set of genes that are turned on or off in that cell. When cells become cancerous, certain of the cell's genes that were turned off may become turned on. Thus, in liver cancer, the cancerous liver cells may take on the characteristics of other types of cells. For example, liver cancer cells sometimes can produce hormones that are ordinarily produced in other body systems. These hormones then can cause certain abnormal blood tests, such as a high red blood count (erythrocytosis), low blood sugar (hypoglycemia) and high blood calcium (hypercalcemia).
Another abnormal blood test, high serum cholesterol (hypercholesterolemia), is seen in up to 10% of patients from Africa with liver cancer. The high cholesterol occurs because the liver cancer cells are not able to turn off (inhibit) their production of cholesterol. (Normal cells are able to turn off their production of cholesterol.)
There is no reliable or accurate screening blood test for liver cancer. The most widely used biochemical blood test is alpha-fetoprotein (AFP), which is a protein normally made by the immature liver cells in the fetus. At birth, infants have relatively high levels of AFP, which fall to normal adult levels by the first year of life. Also, pregnant women carrying babies with neural tube defects may have high levels of AFP. (A neural tube defect is an abnormal fetal brain or spinal cord that is caused by folic acid deficiency during pregnancy.)
In adults, high blood levels (over 500 nanograms/milliliter) of AFP are seen in only three situations:
• Liver cancer
• Germ cell tumors (cancer of the testes and ovaries)
• Metastatic cancer in the liver (originating in other organs)
Several assays (tests) for measuring AFP are available. Generally, normal levels of AFP are below 10 ng/ml. Moderate levels of AFP (even almost up to 500 ng/ml) can be seen in patients with chronic hepatitis. Moreover, many patients with various types of acute and chronic liver diseases without documentable liver cancer can have mild or even moderate elevations of AFP.
The sensitivity of AFP for liver cancer is about 60%. In other words, an elevated AFP blood test is seen in about 60% of liver cancer patients. That leaves 40% of patients with liver cancer who have normal AFP levels. Therefore, a normal AFP does not exclude liver cancer. Also, as noted above, an abnormal AFP does not mean that a patient has liver cancer. It is important to note, however, that patients with cirrhosis and an abnormal AFP, despite having no documentable liver cancer, still are at very high risk of developing liver cancer. Thus, any patient with cirrhosis and an elevated AFP, particularly with steadily rising blood levels, will either most likely develop liver cancer or actually already have an undiscovered liver cancer.
An AFP greater than 500 ng/ml is very suggestive of liver cancer. In fact, the blood level of AFP loosely relates to (correlates with) the size of the liver cancer. Finally, in patients with liver cancer and abnormal AFP levels, the AFP may be used as a marker of response to treatment. For example, an elevated AFP is expected to fall to normal in a patient whose liver cancer is successfully removed surgically (resected).
There are a number of other liver cancer tumor markers that currently are research tools and not generally available. These include des-gamma-carboxyprothrombin (DCP), a variant of the gamma-glutamyltransferase enzymes, and variants of other enzymes (for example, alpha-L-fucosidase), which are produced by normal liver cells. (Enzymes are proteins that speed up biochemical reactions.) Potentially, these blood tests, used in conjunction with AFP, could be very helpful in diagnosing more cases of liver cancer than with AFP alone.

Imaging studies

Imaging studies play a very important role in the diagnosis of liver cancer. A good study can provide information as to the size of the tumor, the number of tumors, and whether the tumor has involved major blood vessels locally or spread outside of the liver. There are several types of studies, each having its merits and disadvantages. In practice, several studies combined often complement each other. On the other hand, a plain X-ray is not very helpful, and therefore, is not routinely done in the diagnostic work-up of liver cancer. Further, there is no practical role for nuclear medicine scans of the liver and spleen in the work-up for liver cancer. Such scans are not very sensitive and they provide no additional information beyond that provided by the other (ultrasound, CT, and MRI) scans.
Ultrasound examination is usually the first study ordered if liver cancer is suspected in a patient. The accuracy of an ultrasound depends very much on the technician and radiologist who perform the study (operator dependent). Studies from Japan and Taiwan report that ultrasound is the most sensitive imaging study for diagnosing and characterizing liver cancer. But you should know that in these studies, highly experienced individuals performed the scans and spent up to one hour scanning each patient suspected of having liver cancer. An ultrasound has the advantages of not requiring intravenous contrast material and not involving radiation. Moreover, the price of an ultrasound is quite low as compared to the other types of scans.
Computerized axial tomography (CT scan) is a very common study used in the U.S. for the work-up of tumors in the liver. The ideal CT study is a multi-phase, spiral CT scan using oral and intravenous contrast material. Pictures are taken in three phases:
• Without intravenous contrast
• With intravenous contrast (enhanced imaging) that highlights the arterial system (arterial phase)
• When the contrast is in the venous phase
The pictures are taken at very frequent intervals (thin slices) as the body is moved through the CT scanner. Many radiologists use a specific protocol that determines how the contrast is infused in relation to how the pictures are taken. Therefore, CT is much less operator-dependent than is ultrasound. However, CT is considerably more expensive. Furthermore, CT requires the use of contrast material, which has the potential risks of an allergic reaction and adverse effects on kidney function.
There are several variations to CT scanning. For example, in a CT angiogram, which is a highly invasive (enters a part of the body) study, intravenous contrast is selectively infused through the hepatic artery (artery to the liver). The purpose is to highlight the vessels for better visualization of them by the CT scan. Also, in Japan, an oily contrast material called lipiodol, which is selectively taken up by liver cancer cells, has been used with CT. The purpose of this approach is to improve the sensitivity of the scan. That is to say, the goal is to increase the percentage of abnormal CT scans in patients who have liver cancer.
Magnetic resonance imaging (MRI) can provide very clear images of the body. Its advantage over CT is that MRI can provide sectional views of the body in different planes. The technology has evolved to the point that the newer MRIs can actually reconstruct images of the biliary tree (bile ducts and gallbladder) and of the arteries and veins of the liver. (The biliary tree transports bile from the liver to the duodenum, the first part of the intestine.) MRI studies can be made even more sensitive by using intravenous contrast material (for example, gadolinium).
MRI scans are very expensive and there is tremendous variability in the quality of the images. The quality depends on the age of the machine and the ability of the patients to hold their breath for up to 15 to 20 seconds at a time. Furthermore, many patients, because of claustrophobia, cannot tolerate being in the MRI scanner. However, the current open MRI scanners generally do not provide as high quality images as the closed scanners do.
Advances in ultrasound, CT, and MRI technology have almost eliminated the need for angiography. An angiography procedure involves inserting a catheter into the femoral artery (in the groin) through the aorta, and into the hepatic artery, the artery that supplies blood to the liver. Contrast material is then injected, and X-ray pictures of the arterial blood supply to the liver are taken. An angiogram of liver cancer shows a characteristic blush that is produced by newly formed abnormal small arteries that feed the tumor (neovascularization).
What, then, is the best imaging study for diagnosing liver cancer? There is no simple answer. Many factors need to be taken into consideration. For example, is the diagnosis of liver cancer known or is the scan being done for screening? What is the expertise of doctors in the patient's area? What is the quality of the different scanners at a particular facility? Are there economic considerations? Does the patient have any other conditions that need to be considered, such as claustrophobia or kidney impairment? Does the patient have any hardware, for example, a pacemaker or metal prosthetic device? (The hardware would make doing an MRI impossible.)
If you live in Japan or Taiwan and have access to a radiologist or hepatologist with expertise in ultrasound, then it may be as good as a CT scan. Ultrasound is also the most practical (easier and cheaper) for regular screening (surveillance). In North America, a multi-phase spiral CT scan is probably the most accurate type of scan. However, for patients with impaired renal function or who have access to a state-of-the-art MRI scanner, the MRI may be the diagnostic scan of choice. Finally, keep in mind that the technology of ultrasound, CT, and MRI is ever evolving with the development of better machines and the use of special contrast materials to further characterize the tumors.

Liver biopsy or aspiration

In theory, a definitive diagnosis of liver cancer is always based on microscopic (histological) confirmation. However, some liver cancers are well differentiated, which means they are made up of nearly fully developed, mature liver cells (hepatocytes). Therefore, these cancers can look very similar to non-cancerous liver tissue under a microscope. Moreover, not all pathologists are trained to recognize the subtle differences between well-differentiated liver cancer and normal liver tissue. Also, some pathologists can mistake liver cancer for adenocarcinoma in the liver. An adenocarcinoma is a different type of cancer, and, as previously mentioned, it originates from outside of the liver. Most importantly, a metastatic adenocarcinoma would be treated differently from a primary liver cancer (liver cancer). Therefore, all of this considered, it is important that an expert liver pathologist review the tissue slides of liver tumors in questionable situations.
Tissue can be sampled with a very thin needle. This technique is called fine needle aspiration. When a larger needle is used to obtain a core of tissue, the technique is called a biopsy. Generally, radiologists, using ultrasound or CT scans to guide the placement of the needle, perform the biopsies or fine needle aspirations. The most common risk of the aspiration or biopsy is bleeding, especially because liver cancer is a tumor that is very vascular (contains many blood vessels). Rarely, new foci (small areas) of tumor can be seeded (planted) from the tumor by the needle into the liver along the needle track.
The aspiration procedure is safer than a biopsy with less risk for bleeding. However, interpretation of the specimen obtained by aspiration is more difficult because often only a cluster of cells is available for evaluation. Thus, a fine needle aspiration requires a highly skilled pathologist. Moreover, a core of tissue obtained with a biopsy needle is more ideal for a definitive diagnosis because the architecture of the tissue is preserved. The point is that sometimes a precise diagnosis can be important clinically. For example, some studies have shown that the degree of differentiation of the tumor may predict the patient's outcome (prognosis). That is to say, the more differentiated (resembling normal liver cells) the tumor is, the better the prognosis.
All of that said, in many instances, there is probably no need for a tissue diagnosis by biopsy or aspiration. If a patient has a risk factor for liver cancer (for example, cirrhosis, chronic hepatitis B, or chronic hepatitis C) and a significantly elevated alpha-fetoprotein blood level, the doctor can be almost certain that the patient has liver cancer without doing a biopsy. The patient and physician should always ask two questions before deciding on doing a liver biopsy:
1. Is this tumor most likely an liver cancer?
2. Will the biopsy findings change the management of the patient?
If the answer to both questions is yes, then the biopsy should be done. Finally, there are two other situations related to liver cancer in which a biopsy may be considered. The first is to characterize a liver abnormality (for example, a possible tumor) seen by imaging in the absence of risk factors for liver cancer or elevated alpha-fetoprotein. The second is to determine the extent of disease when there are multiple areas of abnormalities (possibly tumors) seen by imaging in the liver.
Overall, no blanket recommendation can be given regarding the need for liver biopsy or aspiration. The decision has to be made on an individual basis, depending on the treatment options and the expertise of the medical and surgical teams.

Symptoms and Signs of Liver Cancer

2009-05-24T20:16:00.000+03:00

Symptoms

The initial symptoms (the clinical presentations) of liver cancer are variable. In countries where liver cancer is very common, the cancer generally is discovered at a very advanced stage of disease for several reasons. For one thing, areas where there is a high frequency of liver cancer are generally developing countries where access to healthcare is limited. For another, screening examinations for patients at risk for developing liver cancer are not available in these areas. In addition, patients from these regions actually have more aggressive liver cancer disease. In other words, the tumor usually reaches an advanced stage and causes symptoms more rapidly. In contrast, patients in areas of low liver cancer frequency tend to have liver cancer tumors that progress more slowly and, therefore, remain without symptoms longer.
Abdominal pain is the most common symptom of liver cancer and usually signifies a very large tumor or widespread involvement of the liver. Additionally, unexplained weight loss or unexplained fevers are warning signs of liver cancer in patients with cirrhosis. These symptoms are less common in individuals with liver cancer in the U.S. because these patients are usually diagnosed at an earlier stage. However, whenever the overall health of a patient with cirrhosis deteriorates, every effort should be made to look for liver cancer.
A very common initial presentation of liver cancer in a patient with compensated cirrhosis (no complications of liver disease) is the sudden onset of a complication. For example, the sudden appearance of ascites (abdominal fluid and swelling), jaundice (yellow color of the skin), or muscle wasting without causative (precipitating) factors (for example, alcohol consumption) suggests the possibility of liver cancer. What's more, the cancer can invade and block the portal vein (a large vein that brings blood to the liver from the intestine and spleen). When this happens, the blood will travel paths of less resistance, such as through esophageal veins. This causes increased pressure in these veins, which results in dilated (widened) veins called esophageal varices. The patient then is at risk for hemorrhage from the rupture of the varices into the gastrointestinal tract. Rarely, the cancer itself can rupture and bleed into the abdominal cavity, resulting in bloody ascites.

Signs

On physical examination, an enlarged, sometimes tender, liver is the most common finding. Liver cancers are very vascular (containing many blood vessels) tumors. Thus, increased amounts of blood feed into the hepatic artery (artery to the liver) and cause turbulent blood flow in the artery. The turbulence results in a distinct sound in the liver (hepatic bruit) that can be heard with a stethoscope in about one quarter to one half of patients with liver cancer. Any sign of advanced liver disease (for example, ascites, jaundice, or muscle wasting) means a poor prognosis. Rarely, a patient with liver cancer can become suddenly jaundiced when the tumor erodes into the bile duct. The jaundice occurs in this situation because both sloughing of the tumor into the duct and bleeding that clots in the duct can block the duct.
In advanced liver cancer, the tumor can spread locally to neighboring tissues or, through the blood vessels, to elsewhere in the body (distant metastasis). Locally, liver cancer can invade the veins that drain the liver (hepatic veins). The tumor can then block these veins, which results in congestion of the liver. The congestion occurs because the blocked veins cannot drain the blood out of the liver. (Normally, the blood in the hepatic veins leaving the liver flows through the inferior vena cava, which is the largest vein that drains into the heart.) In African patients, the tumor frequently blocks the inferior vena cava. Blockage of either the hepatic veins or the inferior vena cava results in a very swollen liver and massive formation of ascites. In some patients, as previously mentioned, the tumor can invade the portal vein and lead to the rupture of esophageal varices.
Regarding the distant metastases, liver cancer frequently spreads to the lungs, presumably by way of the blood stream. Usually, patients do not have symptoms from the lung metastases, which are diagnosed by radiologic (x-ray) studies. Rarely, in very advanced cases, liver cancer can spread to the bone or brain.

Risk factors for Liver Cancer

2009-05-24T20:07:00.000+03:00

Hepatitis B infection

The role of hepatitis B virus (HBV) infection in causing liver cancer is well established. Several lines of evidence point to this strong association. As noted earlier, the frequency of liver cancer relates to (correlates with) the frequency of chronic hepatitis B virus infection. In addition, the patients with hepatitis B virus who are at greatest risk for liver cancer are men with hepatitis B virus cirrhosis (scarring of the liver) and a family history of liver cancer. Perhaps the most convincing evidence, however, comes from a prospective (looking forward in time) study done in the 1970's in Taiwan involving male government employees over the age of 40. In this study, the investigators found that the risk of developing liver cancer was 200 times higher among employees who had chronic hepatitis B virus as compared to employees without chronic hepatitis B virus!
Studies in animals also have provided evidence that hepatitis B virus can cause liver cancer. For example, we have learned that liver cancer develops in other mammals that are naturally infected with hepatitis B virus-related viruses. Finally, by infecting transgenic mice with certain parts of the hepatitis B virus, scientists caused liver cancer to develop in mice that do not usually develop liver cancer. (Transgenic mice are mice that have been injected with new or foreign genetic material.)
How does chronic hepatitis B virus cause liver cancer? In patients with both chronic hepatitis B virus and liver cancer, the genetic material of hepatitis B virus is frequently found to be part of the genetic material of the cancer cells. It is thought, therefore, that specific regions of the hepatitis B virus genome (genetic code) enter the genetic material of the liver cells. This hepatitis B virus genetic material may then disrupt the normal genetic material in the liver cells, thereby causing the liver cells to become cancerous.
The vast majority of liver cancer that is associated with chronic hepatitis B virus occurs in individuals who have been infected most of their lives. In areas where hepatitis B virus is not always present (endemic) in the community (for example, the U.S.), liver cancer is relatively uncommon. The reason for this is that most of the people with chronic hepatitis B virus in these areas acquired the infection as adults. However, liver cancer can develop in individuals who acquired chronic hepatitis B virus in adulthood if there are other risk factors, such as chronic alcohol use or co-infection with chronic hepatitis C virus infection.

Hepatitis C infection

Hepatitis C virus (HCV) infection is also associated with the development of liver cancer. In fact, in Japan, hepatitis C virus is present in up to 75% of cases of liver cancer. As with hepatitis B virus, the majority of hepatitis C virus patients with liver cancer have associated cirrhosis (liver scarring). In several retrospective-prospective studies (looking backward and forward in time) of the natural history of hepatitis C, the average time to develop liver cancer after exposure to hepatitis C virus was about 28 years. The liver cancer occurred about eight to 10 years after the development of cirrhosis in these patients with hepatitis C. Several prospective European studies report that the annual incidence (occurrence over time) of liver cancer in cirrhotic hepatitis C virus patients ranges from 1.4 to 2.5% per year.
In hepatitis C virus patients, the risk factors for developing liver cancer include the presence of cirrhosis, older age, male gender, elevated baseline alpha-fetoprotein level (a blood tumor marker), alcohol use, and co-infection with hepatitis B virus. Some earlier studies suggested that hepatitis C virus genotype 1b (a common genotype in the U.S.) may be a risk factor, but more recent studies do not support this finding.
The way in which hepatitis C virus causes liver cancer is not well understood. Unlike hepatitis B virus, the genetic material of hepatitis C virus is not inserted directly into the genetic material of the liver cells. It is known, however, that cirrhosis from any cause is a risk factor for the development of liver cancer. It has been argued, therefore, that hepatitis C virus, which causes cirrhosis of the liver, is an indirect cause of liver cancer.
On the other hand, there are some chronic hepatitis C virus infected individuals who have liver cancer without cirrhosis. So, it has been suggested that the core (central) protein of hepatitis C virus is the culprit in the development of liver cancer. The core protein itself (a part of the hepatitis C virus) is thought to impede the natural process of cell death or interfere with the function of a normal tumor suppressor (inhibitor) gene (the p53 gene). The result of these actions is that the liver cells go on living and reproducing without the normal restraints, which is what happens in cancer.
Alcohol

Cirrhosis caused by chronic alcohol consumption

It is the most common association of liver cancer in the developed world. Actually, we now understand that many of these cases are also infected with chronic hepatitis C virus. The usual setting is an individual with alcoholic cirrhosis who has stopped drinking for ten years, and then develops liver cancer. It is somewhat unusual for an actively drinking alcoholic to develop liver cancer. What happens is that when the drinking is stopped, the liver cells try to heal by regenerating (reproducing). It is during this active regeneration that a cancer-producing genetic change (mutation) can occur, which explains the occurrence of liver cancer after the drinking has been stopped.
Patients who are actively drinking are more likely to die from non-cancer related complications of alcoholic liver disease (for example, liver failure). Indeed, patients with alcoholic cirrhosis who die of liver cancer are about 10 years older than patients who die of non-cancer causes. Finally, as noted above, alcohol adds to the risk of developing liver cancer in patients with chronic hepatitis C virus or hepatitis B virus infections.

Aflatoxin B1

Aflatoxin B1 is the most potent liver cancer-forming chemical known. It is a product of a mold called Aspergillus flavus, which is found in food that has been stored in a hot and humid environment. This mold is found in such foods as peanuts, rice, soybeans, corn, and wheat. Aflatoxin B1 has been implicated in the development of liver cancer in Southern China and Sub-Saharan Africa. It is thought to cause cancer by producing changes (mutations) in the p53 gene. These mutations work by interfering with the gene's important tumor suppressing (inhibiting) functions.

Drugs, medications, and chemicals

There are no medications that cause liver cancer, but female hormones (estrogens) and protein-building (anabolic) steroids are associated with the development of hepatic adenomas. These are benign liver tumors that may have the potential to become malignant (cancerous). Thus, in some individuals, hepatic adenoma can evolve into cancer.
Certain chemicals are associated with other types of cancers found in the liver. For example, thorotrast, a previously used contrast agent for imaging, caused a cancer of the blood vessels in the liver called hepatic angiosarcoma. Also, vinyl chloride, a compound used in the plastics industry, can cause hepatic angiosarcomas that appear many years after the exposure.
Hemochromatosis

Liver cancer will develop in up to 30% of patients with hereditary hemochromatosis. Patients at the greatest risk are those who develop cirrhosis with their hemochromatosis. Unfortunately, once cirrhosis is established, effective removal of excess iron (the treatment for hemochromatosis) will not reduce the risk of developing liver cancer.
Cirrhosis

Individuals with most types of cirrhosis of the liver are at an increased risk of developing liver cancer. In addition to the conditions described above (hepatitis B, hepatitis C, alcohol, and hemochromatosis), alpha 1 anti-trypsin deficiency, a hereditary condition that can cause emphysema and cirrhosis, may lead to liver cancer. Liver cancer is also strongly associated with hereditary tyrosinemia, a childhood biochemical abnormality that results in early cirrhosis.
Certain causes of cirrhosis are less frequently associated with liver cancer than are other causes. For example, liver cancer is rarely seen with the cirrhosis in Wilson's disease (abnormal copper metabolism) or primary sclerosing cholangitis (chronic scarring and narrowing of the bile ducts). It used to be thought that liver cancer is rarely found in primary biliary cirrhosid (PBC) as well. Recent studies, however, show that the frequency of liver cancer in PBC is comparable to that in other forms of cirrhosis.

Surgical Treatment of Hepatocellular Carcinoma ( HCC )

2009-05-11T21:37:00.000+03:00

The treatment options are dictated by the stage of liver cancer and the overall condition of the patient. The only proven cure for liver cancer is liver transplantation for a solitary, small (<3cm)>

Liver resection

The goal of liver resection is to completely remove the tumor and the appropriate surrounding liver tissue without leaving any tumor behind. This option is limited to patients with one or two small (3 cm or less) tumors and excellent liver function, ideally without associated cirrhosis. As a result of these strict guidelines, in practice, very few patients with liver cancer can undergo liver resection. The biggest concern about resection is that following the operation, the patient can develop liver failure. The liver failure can occur if the remaining portion of the liver is inadequate to provide the necessary support for life. Even in carefully selected patients, about 10% of them are expected to die shortly after surgery, usually as a result of liver failure.

When a portion of a normal liver is removed, the remaining liver can grow back (regenerate) to the original size within one to two weeks. A cirrhotic liver, however, cannot grow back. Therefore, before resection is performed for liver cancer, the non-tumor portion of the liver should be biopsied to determine whether there is associated cirrhosis.

For patients whose tumors are successfully resected, the five-year survival is about 30 to 40%. This means that 30 to 40 % of patients who actually undergo liver resection for liver cancer are expected to live five years. Many of these patients, however, will have a recurrence of liver cancer elsewhere in the liver. Moreover, it should be noted that the survival rate of untreated patients with similar sized tumors and similar liver function is probably comparable. Some studies from Europe and Japan have shown that survival rates with alcohol injection or radiofrequency ablation procedures are comparable to the survival rates of those patients who underwent resection. But again, the reader should be cautioned that there are no head-to-head comparisons of these procedures versus resection.

Liver transplantation

Liver transplantation has become an accepted treatment for patients with end-stage (advanced) liver disease of various types (for example, chronic hepatitis B and C, alcoholic cirrhosis, primary biliary cirrhosis, and sclerosing cholangitis). Survival rates for these patients without liver cancer are 90% at one year, 80% at three years, and 75% at five years. Moreover, liver transplantation is the best option for patients with tumors that are less than 5 cm in size who also have signs of liver failure. In fact, as one would expect, patients with small cancers (less than 3 cm) and no involvement of the blood vessels do very well. These patients have a less than 10% risk of recurrent liver cancer after transplant. On the other hand, there is a very high risk of recurrence in patients with tumors greater than 5 cm or with involvement of blood vessels. For these reasons, when patients are being evaluated for treatment of liver cancer, every effort should be made to characterize the tumor and look for signs of spread beyond the liver.

There is a severe shortage of organ donors in the U.S. Currently, there are about 18,000 patients on the waiting list for liver transplantation. About 4,000 donated cadaver livers (taken at the time of death) are available per year for patients with the highest priority. This priority goes to patients on the transplant waiting list who have the most severe liver failure. As a result, in many liver cancer patients, while they are on the waiting list, the tumor may become too large for the patient to benefit from liver transplantation. Doing palliative treatments, such as TACE, while the patient is on the waiting list for liver transplantation is currently being evaluated.

The use of a partial liver from a healthy, live donor may provide a few patients with liver cancer an opportunity to undergo liver transplantation before the tumor becomes too large. This innovation is a very exciting development in the field of liver transplantation.

As a precaution, doing a biopsy or aspiration of liver cancer should probably be avoided in patients considering liver transplantation. The reason to avoid needling the liver is that there is about a 1-4% risk of seeding (planting) cancer cells from the tumor by the needle into the liver along the needle track. You see, after liver transplantation, patients take powerful anti-rejection medications to prevent the patient's immune system from rejecting the new liver. However, the suppressed immune system can allow new foci (small areas) of cancer cells to multiply rapidly. These new foci of cancer cells would normally be kept at bay by the immune cells of an intact immune system.

In summary, liver resection should be reserved for patients with small tumors and normal liver function (no evidence of cirrhosis). Patients with multiple or large tumors should receive palliative therapy with intra-arterial chemotherapy or TACE, provided they do not have signs of severe liver failure. Patients with an early stage of cancer and signs of chronic liver disease should receive palliative treatment and undergo evaluation for liver transplantation.

Is there a role for routine screening for liver cancer?

It makes sense to screen for liver cancer just as we do for colon, cervical, breast, and prostate cancer. However, the difference is that there is, as yet, no cost-effective way of screening for liver cancer. Blood levels of alpha-fetoprotein are normal in up to 50% of patients with small liver cancer. Ultrasound scanning, which is non-invasive and very safe, is, as mentioned before, operator-dependent. Therefore, the effectiveness of a screening ultrasound that is done at a small facility can be very suspect.

Even more disappointing is the fact that no study outside of Asia has shown, on a large scale, that early detection of liver cancer saved lives. Why is that? It is because, as already noted, the treatment for liver cancer, except for liver transplantation, is not very effective. Also, keep in mind that patients found with small tumors on screening live longer than patients with larger tumors only because of what is called a "lead time bias." In other words, they seem to liver longer (the bias) only because the cancer was discovered earlier (the lead time), not because of any treatment given.

Nevertheless, strong arguments can be made for routine screening. For example, the discovery of an liver cancer in the early stages allows for the most options for treatment, including liver resection and liver transplantation. Therefore, all patients with cirrhosis, particularly cirrhosis caused by chronic hepatitis B or C, hemochromatosis, and alcohol, should be screened at six- to 12-month intervals with a blood alpha-fetoprotein and an imaging study. I favor alternating between an ultrasound and CT scan (or MRI). Patients with chronically (long duration) elevated alpha-fetoprotein levels warrant more frequent imaging since these patients are at even higher risk of developing liver cancer.

Hepatocellular Carcinoma ( HCC )

2009-04-12T14:15:00.000+02:00

hepatocellular carcinoma - HCC

What is liver cancer (hepatocellular carcinoma - HCC)?

Liver cancer (hepatocellular carcinoma) is a Cancer arising from the liver. It is also known as primary liver cancer or hepatoma. The liver is made up of different cell types (for example, bile ducts, blood vessels, and fat-storing cells). However, liver cells (hepatocytes) make up 80% of the liver tissue. Thus, the majority of primary liver cancers (over 90 to 95%) arises from liver cells and is called hepatocellular cancer or carcinoma.
When patients or physicians speak of liver cancer, however, they are often referring to cancer that has spread to the liver, having originated in other organs (such as the colon, stomach, pancreas, breast, and lung). More specifically, this type of liver cancer is called metastatic liver disease (cancer) or secondary liver cancer. Thus, the term liver cancer actually can refer to either metastatic liver cancer or hepatocellular cancer. The subject of this article is hepatocellular carcinoma, which I will refer to as liver cancer.

What is the problem of the liver cancer?

Liver cancer is the fifth most common cancer in the world. A deadly cancer, liver cancer will kill almost all patients who have it within a year. In 1990, the World Health Organization estimated that there were about 430,000 new cases of liver cancer worldwide, and a similar number of patients died as a result of this disease. About three quarters of the cases of liver cancer are found in Southeast Asia (China, Hong Kong, Taiwan, Korea, and Japan). Liver cancer is also very common in sub-Saharan Africa (Mozambique and South Africa).
The frequency of liver cancer in Southeast Asia and sub-Saharan Africa is greater than 20 cases per 100,000 population. In contrast, the frequency of liver cancer in North America and Western Europe is much lower, less than five per 100,000 population. However, the frequency of liver cancer among native Alaskans is comparable to that seen in Southeast Asia. Moreover, recent data show that the frequency of liver cancer in the U.S. overall is rising. This increase is due primarily to chronic Hepatits C , an infection of the liver that causes liver cancer.

What are the population characteristics (epidemiology) of liver cancer?

In the U.S. the highest frequency of liver cancer occurs in immigrants from Asian countries, where liver cancer is common. The frequency of liver cancer among Caucasians is the lowest, whereas among African-Americans and Hispanics, it is intermediate. The frequency of liver cancer is high among Asians because liver cancer is closely linked to hepatitis B chronic infection. This is especially so in individuals who have been infected with chronic hepatitis B for most of their lives. If you take a world map depicting the frequency of chronic hepatitis B infection, you can easily superimpose that map on a map showing the frequency of liver cancer.
The initial presentation (symptoms) of liver cancer in patients in areas of high liver cancer frequency is quite different from that seen in low frequency areas. Patients from high frequency areas usually start developing liver cancer in their 40s, and the cancer is usually more aggressive. That is, the liver cancer presents with severe symptoms and is inoperable (too advanced for surgery) at the time of diagnosis. Also, in these areas, the frequency of liver cancer is three to four times higher in men than in women, and most of these patients are infected with chronic hepatitis B. In contrast, liver cancer in lower risk areas occurs in patients in their 50s and 60s and the predominance of men is less striking.

What is the natural history of liver cancer?

The natural history of liver cancer depends on the stage of the tumor and the severity of associated liver disease (for example, cirrhosis) at the time of diagnosis. For example, a patient with a 1 cm tumor with no cirrhosis has a greater than 50% chance of surviving three years, even without treatment. In contrast, a patient with multiple tumors involving both lobes of the liver (multicentric tumors) with decompensated cirrhosis (signs of liver failure) is unlikely to survive more than six months, even with treatment.
What are the predictors of a poor outcome? Our knowledge of the prognosis is based on studying many patients with liver cancer, separating out their clinical characteristics, and relating them to the outcome. Grouped in various categories, the unfavorable clinical findings include;
• Population characteristics (demographics); male gender, older age, or alcohol consumption.
• Symptoms; weight loss or decreased appetite.
• Signs of impaired liver function; jaundice, ascites, or encephalopathy (altered mental state).
• Blood tests; elevated liver tests (bilirubin or transaminase), reduced albumin, elevated AFP, elevated blood urea nitrogen (BUN), or low serum sodium.
• Staging of tumor (based on imaging or surgical findings); more than one tumor, tumor over 3 cm (almost 1¼ inches), tumor invasion of local blood vessels (portal and/or hepatic vein), tumor spread outside of the liver (to lymph nodes or other organs).
There are various systems for staging liver cancer. Some systems look at clinical findings while others rely solely on pathological (tumor) characteristics. It makes the most sense to use a system that incorporates a combination of clinical and pathological elements. In any event, it is important to stage the cancer because staging can provide guidelines not only for predicting outcome (prognosis) but also for decisions regarding treatment.
The doubling time for a cancer is the time it takes for the tumor to double in size. For liver cancer, the doubling time is quite variable, ranging from one month to eighteen months. This kind of variability tells us that every patient with liver cancer is unique. Therefore, an assessment of the natural history and the evaluation of different treatments are very difficult. Nevertheless, in patients with a solitary liver cancer that is less than 3 cm, with no treatment, we can expect that 90% of the patients will survive (live) for one year, 50% for three years, and 20% for five years. In patients with more advanced disease, we can expect that 30% will survive for one year, 8% for three years, and none for five years.

What is fibrolamellar carcinoma?

Fibrolamellar carcinoma is an liver cancer variant that is found in non-cirrhotic livers, usually in younger patients between the ages of 20 and 40 years. In fact, these patients have no associated liver disease and no risk factors have been identified. The alpha-fetoprotein in these patients is usually normal. The appearance of fibrolamellar carcinoma under the microscope is quite characteristic. That is, broad bands of scar tissue are seen running through the cancerous liver cells. The important thing about fibrolamellar carcinoma is that it has a much better prognosis than the common type of liver cancer. Thus, even with a fairly extensive fibrolamellar carcinoma, a patient can have a successful surgical removal.

What's in the future for the prevention and treatment of liver cancer?

Prevention

Worldwide, the majority of liver cancer is associated with chronic hepatitis B virus infection. Today, however, all newborns are vaccinated against hepatitis B in China and other Asian countries. Therefore, the frequency of chronic hepatitis B virus in future generations will decrease. Eventually, perhaps in three or four generations, hepatitis B virus will be totally eradicated, thereby eliminating the most common risk factor for liver cancer.

Some retrospective (looking back in time) studies suggest that patients with chronic hepatitis C who were treated with interferon were less likely to develop liver cancer than patients who were not treated. Interestingly, in these studies, interferon treatment seemed to provide this benefit, even to patients who had less than an optimal antiviral response to interferon. Still, it remains to be seen whether the risk of developing cirrhosis and liver cancer is significantly decreased in prospectively (looking ahead) followed patients who responded to interferon.

One Japanese study has reported that a retinoid derivative (a compound related to vitamin A) was effective in preventing recurrence of liver cancer after resection of the liver. As of now, this compound is not available in the U.S. It would be of great interest to study the use of this compound in conjunction with other palliative therapy for liver cancer.

Treatment

Unfortunately, there have been no significant new developments in the treatment of liver cancer. Medical therapy remains a disappointment. Scientists are working hard, however, to address this problem. For example, anti-angiogenesis compounds, which inhibit blood vessel formation, may hold promise in the treatment of liver cancer since this tumor depends on a rich blood supply. Also, different ways to deliver drugs or treatment to the tumors are being investigated. This includes attaching radioactive material to antibodies that are directed at specific targets in liver cancer cells (immunotherapy).

Problem of the Liver Cancer

2009-04-12T11:51:00.000+02:00

What is the problem of the Liver Cancer?

Liver cancer is the fifth most common cancer in the world. A deadly cancer, liver cancer will kill almost all patients who have it within a year. In 1990, the World Health Organization estimated that there were about 430,000 new cases of liver cancer worldwide, and a similar number of patients died as a result of this disease. About three quarters of the cases of liver cancer are found in Southeast Asia (China, Hong Kong, Taiwan, Korea, and Japan). Liver cancer is also very common in sub-Saharan Africa (Mozambique and South Africa).
The frequency of liver cancer in Southeast Asia and sub-Saharan Africa is greater than 20 cases per 100,000 population. In contrast, the frequency of liver cancer in North America and Western Europe is much lower, less than five per 100,000 population. However, the frequency of liver cancer among native Alaskans is comparable to that seen in Southeast Asia. Moreover, recent data show that the frequency of liver cancer in the U.S. overall is rising. This increase is due primarily to chronic Hepatits C , an infection of the liver that causes liver cancer.

وظائف الكبد

2007-07-24T12:20:00.001+03:00

الكـبد عضو هام جدا بجسم الانسان ولا يمكن الاستغناء عنه لاهميته الشديده
الوضع التشريحى يوجد فى بطن الانسان باعلا الجانب الايمن تحت الحجاب الحاجز مباشرا يتكون الكبد من جزئين اساسيان هما الفص الايمن والفص الايسر الفص الايمن وهو الفص الاكبر حجما وعدد خلايه اكثر من الفص الايسر ينقسم كل فص الى اجزاء صعيرة الدورة الدموية للكبد يستقبل الكبد الدم الرئيسى من الوريد البابى الذى يجمع الدم من الجهاز الهضمى ( المعدة – الامعاء الدقيقة – الامعاء الغليظة – المستقيم – الطحال ) وايضا يستقبل الدم من الشريان الكبدى ويصب الدم من الفصين الايمن والايسر فى الوريد الاجوف السفلى ما هى فؤائد الكـبد
يعتبر الكبد مصنع كبير للكمياء الحيوية فهو يقوم بالعمليات الاتية
تخليق البروتنات لجسم الانسان تكوين العوامل اللازمة لتجلط الدم تحويل عناصر الطعام من صورة الى أخرة من تبسيط وتعقيد لمركبات الطعام تخزين بعض عناصر الطعام المركبة مثل الجليكوجين التعامل مع الادوية فى تنشيطها وابطال مفعولها الضار التعامل مع السموم وابطال مفعولها الضار تكوين العصارة الصفراوية الهامة لهضم الطعام تخليق وتجديد خلايا الكبد التالفة