All About Hepatits B

"The deadly disease called hepatitis B" by Ashoke K. Roy

2014-01-16T10:11:00.001-08:00

Hepatitis B is a liver disease caused by HBV infection. HBV can cause short-term (acute) illness that may lead to flu-like symptoms (loss of appetite, diarrhoea and vomiting, fever) and jaundice (yellow skin or eyes), and long-term (chronic) illness that may lead to liver damage (cirrhosis), liver cancer and death. Individuals with chronic infection may become carriers capable of spreading the disease to others.

World-wide, the disease is a major health problem: more than 2 billion people have been infected with HBV, about 400 million are estimated to be HBV carriers, and HBV-associated liver cancer and cirrhosis account for over 1 million deaths each year. About 75 per cent of the long-term carriers live in Asia Pacific.

Global Situation: It is estimated that at least 1 million people worldwide die prematurely each year as a result of Hepatitis B infection and there are more than 350 million long-term carrier of the disease.

* High endemicity - Hepatitis B is highly endemic in developing regions with high population densities such as South East Asia, parts of China, sub-Saharan Africa and the Amazon Basin. In these areas, 70–95 per cent of the population show serological evidence of previous or current HBV infection. Most infections occur during infancy or childhood. Carrier rates are therefore also high, at 8–20 per cent of the population.

* Intermediate endemicity - In parts of Eastern and Southern Europe, the Middle East, Japan, North Africa, Central and Latin America. 20–55 per cent of the population have HBV markers of infection and 2–7 per cent are carriers. There is a high proportion of infection in children, but infection in adults is also quite common.

* Low endemicity - The endemicity of HBV is low in North America, Northern and Western Europe and Australia. In these regions, HBV infects 4–6 per cent of the population. The disease most commonly affects adolescents and young adults. 0.5–2 per cent of the population are chronic carriers.The patterns of HBV prevalence and the incidence of hepatitis B are constantly shifting. For example, in the 1980s in the US, the number of hepatitis B infections in homosexuals showed a significant decrease, yet the number of infections in heterosexuals increased significantly.Changes in living standards, behavior and vaccination policies can all influence disease patterns.

Population groups at high-risk: In low endemicity countries, the prevalence of hepatitis B in some population groups may be markedly higher than average. For example, in the US 70–85 per cent of immigrants from high endemicity areas have HBV markers indicating past infection, and about 13 per cent are carriers.

Other groups with a high prevalence of hepatitis B include the institutionalized mentally retarded and the staff caring for them, homosexual males, intravenous drug abusers, household contacts of carriers, patients who require regular blood transfusions or hemodialysis, prisoners and prison staff, health care workers, people with sexually transmitted diseases, prostitutes and the sexually promiscuous. All of these are at increased risk as their activities may bring them into contact with infected body fluids.

Morbidity and mortality: HBV is one of the most significant viruses in terms of world-wide morbidity and mortality. In fact, the data shown here may be grossly underestimating the problem.

The virus has infected over 2000 million people and there are over 350 million chronic carriers. The pool of carriers is increasing by 2–3 per cent a year. These carriers make up an enormous reservoir from which hepatitis B can spread to susceptible individuals.

HBV is responsible for 1 million deaths a year, the majority of fatalities being due to cirrhosis and primary hepatocellular carcinoma (PHC), a form of liver cancer. Epidemiological data indicate that there is a consistent and specific causal association between infection with HBV and hepatocellular carcinoma.

Hepatocellular carcinoma is the most common form of primary liver cancer, and one of the ten most common cancers in the world. Up to 80 per cent of the world’s primary liver cancer cases are attributed to HBV. HBV is second in importance only to tobacco among the known human carcinogens. After introduction of vaccine in America in 1981 the incidence of Hepatitis B started to fall down from 1985.

In Bangladesh: Not very well studied. Several studies found huge number of patients and carriers. It is estimated that 7-9 per cent of our population may be suffering from the disease or carrying the virus. This is a great cause of concern.

HBV and the chronic carrier state: Every year millions of people are newly infected by the hepatitis B virus. About two-thirds of infected adults will show clinical symptoms which can vary in seriousness from mild to severe. In a small but significant number of cases, the infection is fatal.

Some people who are infected are unable to mount an effective immune response to eliminate the virus. They become long-term HBV carriers.

The risk of becoming a chronic carrier depends on age. Up to 80–90 per cent of newborns and infants infected with HBV may become long-term chronic hepatitis B patients. 5–10 per cent of infections in adults will also lead to a chronic carrier state. The milder the primary infection, the greater the risk of becoming a chronic carrier. Most chronic HBV carriers do not suffer from any clinical symptoms and seem perfectly healthy. However, their livers are being progressively damaged and, eventually, severe chronic liver disease may result.

Chronic carriers are also able to infect others and therefore represent a constant public health risk. It is estimated that there are over 350 million carriers of HBV world-wide - that is about 5 per cent of the world’s population!

How it spreads: HBV is spread through contact with the blood or other body fluids of an infected person, for example, by sexual contact, from mother to child during birth, by intravenous drug use with infected needles or by needle-stick injuries in certain occupations, even sharing toothbrushes or razors. In travelers from developed countries it is the second most frequent vaccine preventable disease.

Prevention of hepatitis B : Vaccination is the most effective way of preventing hepatitis B disease. Vaccination against hepatitis B is recommended for inclusion in childhood immunization programs worldwide and for groups at risk of HBV infection (e.g. healthcare workers and travelers to countries with a high prevalence of hepatitis B). More than 100 countries world wide have implemented this program already. Hepatitis B vaccines are the first which have been shown to prevent cancer (liver cancer).

Vaccination: Vaccination is the most effective and convenient way of preventing hepatitis B disease and the chronic carrier state or liver cancer that can result from it.

From that point of view Hepatitis B vaccine is the first anti-cancer vaccine.

Protection from acute and chronic infection, as well as clinical illness, is virtually complete among persons who develop a protective antibody response (anti-HBs>=10 mIU/ml) following vaccination. It is generally accepted that the threshold anti-HBs titer for protection is 10 mIU/ml. However, some health authorities (e.g. in the UK) have set the limit more conservatively at 100 mIU/ml.

The magnitude of the antibody response induced by the primary vaccination series is predictive of the persistence of detectable antibodies. Current follow-up studies indicate that protection from clinically significant HBV infection and chronic carriage remains intact for at least 15 years in immunocompetent individuals, and that immune memory continues to provide protection even when anti-HBs levels have become undetectable.

Widespread use of hepatitis B vaccine has been shown to dramatically reduce hepatitis B virus infection and the development of liver cancer from chronic hepatitis B infection. Consequently, the Centres for Disease Control and Prevention (CDC) and the World Health Organization (WHO) regard hepatitis B vaccine as the first anti-cancer vaccine since it prevents this serious consequence of hepatitis B infection. The WHO states that hepatitis B vaccine is the first and currently the only vaccine against a major human cancer.

The two main types of hepatitis B vaccine currently available are-

* plasma-derived vaccines

* genetically-engineered vaccines

Plasma-derived vaccines: Preparation of a plasma-derived vaccine.

During an HBV infection, large quantities of the surface antigen HBsAg are synthesized in the liver and released into the blood stream. This phenomenon is exploited in the production of plasma derived vaccines, when HBsAg particles are isolated from the blood of chronic carriers, purified and incorporated into a vaccine.

Plasma derived vaccines were the first vaccines to be used against hepatitis B. They have since been widely used and have been found to be safe and effective. However, with a production cycle of 1 year, supplies of these plasma-derived vaccines were limited, and there were widespread, but unjustified, fears that the vaccines could be contaminated with other blood-borne diseases such as HIV. Also the complex production procedures and lengthy testing mean that plasma-derived vaccines were expensive.

Genetically engineered vaccines: Preparation of a genetically-engineered vaccine.

The discovery of the gene expressing HBsAg in the 1970s together with developments in molecular biology have made it possible to produce genetically-engineered vaccines against hepatitis B. Today large quantities of HBsAg can be generated by inserting the gene expressing HBsAg into a suitable vehicle such as yeast. As the vehicle multiplies, the implanted DNA induces the production of HBsAg. The surface antigen is then extracted and purified and incorporated into a vaccine.

These genetically-engineered vaccines provide effective protection against hepatitis B. They also have a number of advantages compared to plasma-derived vaccines:

* They can be produced more quickly.

* They can be manufactured in larger quantities.

* They are produced from cells which contain only part of the genetic code of the hepatitis B virus, so they are free from infectious virus particles.

* Their production does not rely on the availability of carrier plasma, with its associated risk of contaminants.

Treatment: Till last year the treatment option for Hepatitis B was very limited. Only Interferon was the drug that was very expensive, toxic and the treatment success was less than 20 per cent. Now an oral medicine is available that developed in the laboratory of GlaxoSmithKline. It available at an affordable price and well tolerated. Still prevention is better and preferable. Emphasis should be given on Vaccination. Prevention is better than cure. Vaccination is preferred and easy means of preventing the deadly disease.

Prevention and Vaccination

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Prevention Measures

Hepatitis B is a vaccine-preventable disease. There is a safe and effective vaccine to protect infants, children and adults from hepatitis B. Billions of doses have been given worldwide.

All sex partners, family and close household members of a chronically infected person should be screened and vaccinated. Reassure patients and families that hepatitis B is not casually transmitted - it is spread through blood, not by coughing, sneezing, hugging or sharing food.

Additional Prevention Measures

In addition to vaccination, there are other simple ways to help stop the spread of hepatitis B:

§ Wash your hands thoroughly after any potential exposure

§ Practice safe sex with all partners

§ Avoid direct contact with blood and bodily fluids

§ Clean up blood spills with a fresh diluted bleach solution

§ Cover all cuts carefully

§ Avoid sharing sharp items such as razors, nail clippers, toothbrushes, and earrings or body rings

§ Discard sanitary napkins and tampons into plastic bags

§ Avoid illegal street drugs (injecting, inhaling, snorting, popping pills)

§ Do not donate blood or body organs

§ Make sure new, sterile needles are used for ear or body piercing, tattoos, and acupuncture

Hepatitis B Vaccine

Side Effects and Safety - Vaccine Recommendations - Vaccine Schedule - Vaccine Cost - Approved Hepatitis B Vaccines

It takes only 3 shots to protect your`self and your loved ones against hepatitis B for a lifetime.

In 1981, the Food and Drug Administration approved the first vaccine for hepatitis B, which was plasma-derived (i.e. made from blood products). This vaccine was discontinued in 1990 and is no longer available in the U.S.

The currently used hepatitis B vaccines are made synthetically (i.e. they do not contain blood products) and have been available in the U.S. since 1986. You cannot get hepatitis B from the vaccine.

This safe and effective vaccine is recommended for all infants at birth and for children up to 18 years. Adults, especially those who fall into a high-risk group, should also seriously consider getting the hepatitis B vaccine.

Vaccine Side Effects and Safety

Common side effects include soreness, swelling and redness at the injection site. The vaccine may not be recommended for those with documented yeast allergies or a history of an adverse reaction to the vaccine.

The Hepatitis B vaccine is considered one of the safest and most effective vaccines ever made. Numerous studies looking at the vaccine's safety have been conducted by the Centers for Disease Control, World Health Organization, and other professional medical associations. They have not found any evidence that the vaccine causes sudden infant deaths (SIDs), multiple sclerosis, or other neurological disorders.

Vaccine Recommendations

The hepatitis B vaccine is recommended specifically for all infants and children by the Centers for Disease Control and the American Academy of Pediatrics. The CDC also recommends that adults in high-risk groups be vaccinated.

The following list is a general guide for vaccination, but since every person is at some risk for infection, these guidelines should be individualized for each situation.

§ All infants at birth and all children up to 18 years.

§ Health care professionals and emergency personnel.

§ Sexually active teens and adults

§ Men who have sex with men.

§ Sex partners or close family/household members living with an infected person.

§ Families considering adoption, either domestic or international.

§ Travelers to countries where hepatitis B is common (Asia, Africa, South America, the Pacific Islands, Eastern Europe, and the Middle East).

§ Patients with kidney disease or undergoing dialysis.

§ Residents and staff of correctional facilities and group homes.

§ Any person who may fall into a high risk group due to occupation or lifestyle choices.

Vaccine Schedule

The vaccine is readily available at your doctor's office or local health clinic. Three doses are generally required to complete the hepatitis B vaccine series, although there is an accelerated two-dose series for adolescents.

§ First Injection - At any given time

§ Second Injection - At least one month after the first dose

§ Third Injection - Six months after the first dose

Cost of Vaccine

The three-shot vaccine series for children in the United States usually costs $75 to $165, but this can vary. Infants up to age 18 months, and sometimes older children, can receive the vaccine free of charge from most local public health clinics.

Insurance companies will usually cover the cost of vaccines for infants and children. There is also a federal program to help cover the cost of children's vaccines.

The hepatitis B vaccine costs more for adults. If an adult is in a high-risk group, the cost may be also covered by insurance. Contact your insurance company for more information about the hepatitis B vaccine.

Approved Hepatitis B Vaccines

There are currently two commercial vaccines used to prevent hepatitis B infection among infants, children and adults in the United States. They are both manufactured using recombinant technology and neither contains blood products. You cannot get hepatitis B from these vaccines.

§ Engerix-B, produced by GlaxoSmithKline

§ Recombivax HB, produced by Merck

§ There is also a combination vaccine for hepatitis A and B available for adults: TwinRix, produced by GlaxoSmithKline.

Treatment Options

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Approved Drugs for Adults

The future looks bright for individuals living with chronic hepatitis B. Only a decade ago there were no treatment options. Although there is still no complete cure for hepatitis B, there are 6 approved drugs for adults (2 for children) and many promising new drugs in development. Current treatments seem to be most effective in those who show signs of active liver disease

Not every person with chronic hepatitis B needs to be on medication. You should talk to your doctor about whether you are a good candidate for drug therapy or a clinical trial. Be sure that you understand the pros and cons of each treatment option.

Whether you decide to start treatment or not, it is very important to be seen by a liver specialist or doctor knowledgeable about hepatitis B on a regular basis.

Approved Hepatitis B Drugs in the United States

§ Interferon-alpha (Intron A) is given by injection several times a week for six months to a year, or sometimes longer. The drug can cause side effects such as flu-like symptoms, depression, and headaches. Approved in 1991 and available for both children and adults.

§ Pegylated Interferon (Pegasys) is given by injection once a week usually for six months to a year. The drug can cause side effects such as flu-like symptoms, depression and other mental health problems. Approved May 2005 for adults.

§ Lamivudine (Epivir-HBV, Zeffix, or Heptodin) is a pill that is taken once a day, with almost no side effects, for at least one year or longer. The possible development of hepatitis B virus mutants during and after treatment is a concern. Approved in 1998 and available for both children and adults.

§ Adefovir dipivoxil (Hepsera) is a pill taken once a day, with few side effects, for at least one year or longer. Kidney problems can occur while taking the drug and is a concern, but are reversible once the drug is stopped. Approved September 2002 for adults. Pediatric clinical trials are being planned.

§ Entecavir (Baraclude) is a pill taken once a day, with almost no side effects for up to one year. It is considered to be the most potent oral antiviral drug for chronic hepatitis B to date. Approved April 2005 for adults. Pediatric clinical trials may be planned for the future.

§ Telbivudine (Tyzeka, Sebivo) is a pill taken once a day, with almost no side effects for up to one year. Studies have shown that it rapidly and profoundly suppresses HBV levels. Approved October 2006 for adults.

Although the FDA has approved these six drugs for chronic hepatitis B, they do not provide a complete cure, except in rare cases (a "cure" generally means that a person loses the hepatitis B virus and develops protective surface antibodies).

The drugs, however, significantly decrease the risk of liver damage from the hepatitis B virus by slowing down or stopping the virus from reproducing. As with HIV, it appears that combination therapy will probably be the most effective method of combating chronic hepatitis B infections.

Who Should Be Treated

The decision of whether to start treatment (or enroll in a clinical trial) should be based on careful evaluation of your physical exam, blood tests, and liver biopsy (if one is done). Be sure you see a liver specialist (hepatologist) for the most current information about hepatitis B therapies.

Studies show that the current treatments appear to be of greatest benefit to those who show signs of active liver disease:

§ Elevated liver enzymes (ALT)

§ Positive blood tests for:
Hepatitis B virus (HBsAg)
Hepatitis B e-antigen (HBeAg)

§ Elevated levels of hepatitis B DNA

Some doctors may order a liver biopsy (this involves taking a small sample of your liver to examine under the microscope) to help decide whether treatment is needed, but this practice is not as common as it used to be.

It is always a good idea to get a second opinion before starting any treatment.

Hepatitis B Clinical Trials

The future is bright for people with chronic hepatitis B, thanks in a large part to advancements in medical science. All drugs must go through a testing process, which involves three phases of clinical trials, to evaluate its safety and effectiveness before being approved.

Volunteering for a clinical trial program can be very valuable. Expensive blood work, treatment medications, and doctor’s visits are usually provided free of charge for those accepted into a study. Clinical trials also provide the opportunity to potentially benefit from the latest advances in medical science.

Compounds in Development for Chronic Hepatitis B

Updated July 2007

FAMILY/DRUG NAME	MECHANISM	COMPANY	STATUS
Interferons - Mimic naturally-occurring, infection-fighting immune substance produced in the body
Intron A (Interferon alfa-2b	Immunomodulator	Schering-Plough Madison, NJ	FDA Approved 1991
Pegasys (Peginterferon alfa-2a)	Immunomodulator	Roche Switzerland	FDA Approved 2005
There are other brands of interferon approved for HCV treatment, but they have not been FDA-approved for HBV: Wellferon (Glaxo), Roferon(Hoffman-La Roche), and Infergen (Amgen)
Nucleoside Analogues - Interfere with the viral DNA polymerase enzyme used for hepatitis B virus reproduction
Epivir-HBV (Lamivudine)	Inhibits viral DNA polymerase	GlaxoSmithKline Philadelphia, PA	FDA Approved 1998
Hepsera (Adefovir Dipivoxil)	Inhibits viral DNA polymerase	Gilead Foster City, CA	FDA Approved 2002
Baraclude (Entecavir)	Inhibits viral DNA polymerase	Bristol-Myers Squibb Princeton, NJ	FDA Approved 2005
Tyzeka Sebivo (Europe) (Telbivudine)	Inhibits viral DNA polymerase	Idenix Cambridge, MA	FDA Approved 2006
Emtricitabine (FTC)	Inhibits viral DNA polymerase	Gilead Foster City, CA	Phase III
Clevudine (L-FMAU) Levovir (S. Korea)	Inhibits viral DNA polymerase	Pharmasset Princeton, NJ Bukwang South Korea Eiasai, Japan	Phase III, USA Approved S. Korea (Nov. 2006)
Viread (Tenofovir)	Inhibits viral DNA polymerase	Gilead Foster City, CA	Phase III
Valtorcitabine (monoval LdC)	Inhibits viral DNA polymerase	Idenix Cambridge, MA	Phase II
Amdoxovir (DAPD)	Inhibits viral DNA polymerase	RFS Pharm LLC Tucker, GA	Phase II
ANA 380 (LB80380)	Inhibits viral DNA polymerase	Anadys San Diego, CA	Phase II
Pradefovir (Remofovir)	Inhibits viral DNA polymerase	Schering-Plough Madison, NJ	Phase II
RCV (Racivir)	Inhibits viral DNA polymerase	Pharmasset Princeton, NJ	Phase II
Non-Nucleoside Antivirals - Interfere with proteins involved in viral reproduction
NOV-205 (BAM 205)	Small Molecule	Novelos Newton, MA	Approved in Russia
HepeX-B (XTL-001)	Human monoclonal antibodies	XTL Biopharm and Cubist Pharm, Cambridge, MA	Phase II/III Orphan drug approval in US for liver cancer
Nitazoxanide (Alinia)	Small Molecule	Romark Labs Tampa, FL	Phase II Egypt
UT 231-B *Discovered by HBF Scientists	Small Molecule	United Therapeutics Silver Spring, MD	Preclinical HBV (Phase II HCV)
Bay 41-4109	Inhibits viral nucleocapsid	Bayer AG Germany	Preclinical
Non-Interferon Immune Enhancers - Boost T-cell infection-fighting immune cells and natural interferon production
EHT899	Oral Viral Protein	Enzo Biochem New York, N.Y.	Phase II Israel
Zadaxin (Thymosin alpha-1)	Immune stimulator	SciClone San Mateo, CA	Orphan drug approval in US for liver cancer
Hi-8 HBV	Therapeutic HBV Vaccine	Oxxon U.K.	Phase II
HepX (eiRNA)	Expressed Interfering RNA	Nucleonics Horsham, PA	Phase I
HepaVaxx B	Therapeutic HBV Vaccine	Virexx Canada	Phase I
HBV Core Antigen Vaccine	Therapeutic HBV Vaccine	Emergent Europe U.K.	Phase I
SpecifEx-HepB	Immunological Cell Transfer	Chromos Burnaby, BC	Preclinical/ Phase I
Post-Exposure and/or Post-Liver Transplant Treatment
HyperHEP S/D	HBV Immuneglobulin	Talecris RTP, NC	FDA Approved 1977
Nabi-HB	HBV Immuneglobulin	Nabi Boca Raton, FL	FDA Approved 1999
Hepa Gam B	HBV Immuneglobulin	Cangene Canada	FDA Approved 2006

Children and HBV

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Hepatitis B does not usually affect a child’s normal growth and development. Most children with chronic hepatitis B infections will enjoy long and healthy lives. Unlike other chronic medical conditions, there are generally no physical disabilities associated with hepatitis B, nor are there usually any physical restrictions for these children.

As a parent, you can take comfort from the fact that every child presents unique challenges. Therefore, your child with hepatitis B is just like any other child. The challenges of raising a child with hepatitis B are manageable if you are well informed and use common sense.

Adoption

The key to successful adoption of a child with hepatitis B is to be prepared with accurate information about the disease, and to protect yourself and other members of your household with the hepatitis B vaccine prior to the child's arrival.

International and Domestic Adoption

Many people wish to adopt children from countries where hepatitis B infections are common: Asia, South America, Eastern Europe, and some parts of Africa. Children from these regions are often infected with the virus from their birth mothers who have hepatitis B and unknowingly pass the disease on to their children during delivery. In addition, many of these countries re-use needles for medications or blood tests, a practice that places children at risk if they have not already been infected at birth.

Domestic adoptions also present some risk to potential adoptive families. Children born to women in high-risk groups (e.g. illicit drug users, multiple sexual partners, etc.) could have been infected with hepatitis B at birth. In addition, children from group homes are at increased risk for hepatitis B infection.

Hepatitis B Testing

Your agency should be able to tell you if a child has been tested for hepatitis B. With an international adoption, it is advised that you do not request that your child be tested since the blood test itself could be a source of infection.

Reassurance for Adoptive Parents

Finding out that the child you wish to adopt has chronic hepatitis B can be upsetting, but should not be cause for alarm or stopping an adoption. We hope that a hepatitis B diagnosis will not change your decision to adopt a child. You can be reassured that most children will enjoy a long and healthy life. Hepatitis B does not usually affect a child's normal growth and development, and there are generally no physical disabilities or restrictions associated with this diagnosis.

Advice for Parents

Parents face a whole host of issues when making the decision to raise children. A child with hepatitis B presents new challenges, but they are manageable if you are well informed and use common sense.

The Hepatitis B Foundation has compiled a list of useful guidelines that may be helpful. Since each family is unique, and each community is different, please adjust your decisions accordingly.

Avoid the Spread of Hepatitis B

All parents, siblings, and other household members should be vaccinated. Extended family members, childcare providers, family, friends, and others should consider vaccination if they have, frequent and close contact with your child.

Know the Facts

If people are unfamiliar with hepatitis B, there is a possibility they will become alarmed when told your child has chronic hepatitis B. The key to reducing people's anxiety is to give them clear, simple facts.

§ Hepatitis B is not transmitted casually. It cannot be spread through the sharing of toys, sneezing, coughing, spitting, or hugging.

§ Hepatitis B is spread through blood and infected bodily fluids. Therefore, it could be spread through bites and scratches that result in broken skin.

§ Inform people that there is a safe hepatitis B vaccine and that the American Academy of Pediatrics recommends that all infants and children up to age 18 years be vaccinated.

Know the Risk

In making the decision about telling others, be sure to consider whether your child is at high or low risk for exposing others to his or her blood (e.g. consider age, frequency of accidents, nosebleeds, biting, etc.). Consider the degree of risk a person has for exposure (frequent vs. occasional contact), and whether a person or child may have already been vaccinated.

Although there is no specific law that addresses hepatitis B, the Americans with Disabilities Act (1991) is a federal law that may protect children and adults with hepatitis B from discrimination.

Telling Others

Use common sense in deciding who you should tell about your child's hepatitis B. Once you tell, you can't take it back. So take your time and choose wisely as you decide who can be trusted with this information.

Fortunately, most children are now vaccinated against hepatitis B, so the risk of your child infecting others is reduced. Most states also require the hepatitis B vaccine for school entry. Although you do not necessarily have a "duty" to inform people of your child's hepatitis B, there may be situations where it is wise to disclose your child's diagnosis.

If possible, give literature to reinforce your facts. The Hepatitis B Foundation publishes free educational literature that you can request to give other parents, teachers, or school nurses.

What Should You Say?

Know your facts, use simple explanations, and remain calm. Emphasize that your child is healthy and poses no risk if blood accidents are handled carefully. Remind people (and health care providers) that blood is a two-way street. Other children may have unknown infections that can be spread to your child, therefore, the blood of all children should be handled carefully.

In addition, the hepatitis B vaccine is recommended for all infants and children up to 18 years. Therefore, most children should already be vaccinated and protected against hepatitis B.

Universal Precautions

The Centers for Disease Control (CDC) recommends that everyone use "universal precautions" for any accident. This means that the blood and bodily fluids of all adults and children should be treated as if it is potentially infectious.

Universal precautions (or "standard precautions") should be followed for ALL accidents, not just the blood of those with known chronic hepatitis B infection.

Cleaning Up Blood Spills

Avoid direct contact with blood, vomit, diarrhea and other bodily secretions, and ensure that others will not come into contact with them either.

§Clean all spills with a diluted solution of bleach (mix one part fresh household bleach with nine parts water).

§Discard cleaning materials into a plastic bag and tie securely. Dispose of properly in the garbage can.

§Wash your hands thoroughly with soap and warm water.

PKIDs Pediatric Hepatitis Report

Additional information for parents can be found in the Pediatric Hepatitis Report, which is the first-ever, comprehensive resource about children living with hepatitis B and C. Information about hepatitis B, from transmission to diagnosis, to treatment and civil rights protections is included in this excellent publication. It is published by the national non-profit PKIDs (Parents of Kids with Infectious Diseases).

Approved Drugs for Children

Chronic hepatitis B is normally a mild disease in children and teens. Most children can expect to live full, healthy lives unmarked by visible symptoms. In some children, however, the virus can cause serious liver damage. These children will need medical intervention and treatment.

ALL children with chronic hepatitis B should be seen regularly by a pediatric liver specialist or knowledgeable doctor whether they are on treatment or not. Visits may be every six months or once a year, depending on your child's situation. A physical exam, blood tests, and possible ultrasounds of the liver are part of the usual visit.

Approved Treatments

There are currently two approved treatment options available in the United States for children with chronic hepatitis B.

Interferon alpha (Intron A) is an injection usually given three times a week for 6 months to a year. Children generally experience fewer side effects than adults, but they can include flu-like symptoms.

Lamivudine (Epivir-HBV, Zeffix, Heptodin) is a pill that is taken once a day for at least one year or more. There are almost no side effects.

Not every child (or adult) with chronic hepatitis B needs to be treated. A pediatric liver specialist should evaluate your child to see if she or he is a candidate for treatment based on a physical exam, blood tests, and other test results. Treatment appears to be of greatest benefit to those who show signs of active liver disease.

Disclosing Your Child's Diagnosis

If you decide to disclose your child's hepatitis B, remain calm, provide literature to reinforce the facts, and give the school a letter from your child's doctor stating that s/he is healthy and poses no risk to the other children if appropriate precautions are maintained. Most states require hepatitis B vaccination prior to school entry, so this reduces any potential risk to other students.

We recommend the following when disclosing your child's hepatitis B to school officials:

§ Stress the importance of confidentiality and universal precautions to protect your child from social discrimination.

§ Remind school officials that hepatitis B is transmitted through exposure to blood; it is not transmitted casually.

§ Explain that hepatitis B is not the only blood-borne disease that puts children at risk.

§ Consider saying "Treat my child as you should treat every child — with care. You know what risk my child poses, but you don't know the risk that other children might present."

Living with Hepatitis B

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Adults and HBV

Will I recover?
The first question most people ask is whether or not they will recover from a hepatitis B infection. The answer is directly related to that age at which a person is infected. Most infected adults will recover without any problems, but unfortunately, most infected babies and children will develop chronic hepatitis B infections.

Acute Vs. Chronic

A hepatitis B infection is considered to be “acute” during the first 6 months after being exposed. This is the average period of time it takes to recover from a hepatitis B infection. If you still test positive for the hepatitis B virus (HBsAg+) after 6 months, you are considered to have a "chronic" hepatitis B infection, which can last a lifetime.

What should I do if I am diagnosed with chronic hepatitis B?
Make an appointment with a hepatologist (liver specialist) or gastroenterologist familiar with hepatitis B. This specialist will order blood tests and possibly a liver ultrasound to evaluate your hepatitis B status and the health of your liver. Your doctor will probably want to see you at least once or twice a year to monitor you and determine if you would benefit from treatment.

Most people with chronic hepatitis B can expect to live long, healthy lives. It is important to know that you can pass the virus along to others, even if you don’t feel sick. This is why it’s so important that you make sure that all close household contacts and sex partners are vaccinated against hepatitis B.

Consider following these helpful tips:

§ Avoid alcohol and smoking, as they can be extremely harmful to a liver already infected with the hepatitis B virus.

§ Talk to your doctor before taking any prescription, over the counter medication, or herbal remedies.

§ Although there is no special diet for people who have chronic hepatitis B, a healthy, well-balanced diet that is low-fat and includes plenty of vegetables is recommended.

§ Avoid eating raw shellfish, since they can contain bacteria that are harmful to your liver.

Is there a cure for chronic hepatitis B?
Right now, there is no cure for chronic hepatitis B, but the good news is there are treatments that can help slow the progression of liver disease by slowing down the virus. If there is less hepatitis B virus being produced, then there is less damage being done to the liver. Sometimes these drugs can even get rid of the virus, although this is not common.

With all of the new exciting research, there is great hope that a complete cure will be found for chronic hepatitis B in the near future.

Should I be on medication?
It is important to understand that not every person with chronic hepatitis B needs to be on medication. You should talk to your doctor about whether you are a good candidate for drug therapy or a clinical trial. Be sure that you understand the pros and cons of each treatment option. Whether you decide to start treatment or not, you should be seen regularly by a liver specialist or a doctor knowledgeable about hepatitis B.

Treatment of Liver Cancer

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Early diagnosis and aggressive intervention are key to improving the prognosis of those diagnosed with liver cancer. Promising advances in the treatment of liver cancer are also giving patients new hope. Treatment of liver cancer is particularly challenging when compared with other types of cancer because in addition to the cancer itself, many patients have livers that have sustained damaged by chronic hepatitis B resulting in cirrhosis and various degrees of liver failure.

For each individual patient, the potential benefits of the various treatment options must be balanced with the risk of liver failure and how it affects the patient's quality of life.

Surgical Treatment

When the tumor is small or deemed surgically resectable, and the patient's liver condition is deemed fit for the planned resection, surgical removal offers the best chance for long-term survival. Despite complete removal of the tumor, patients are still at risk for recurrent disease, and they need to be followed closely long-term, especially during the first year when the risk of recurrence is greatest.

Nonsurgical Treatment

For patients who are not suitable resection candidates for anatomic or medical reasons, a number of treatment options, though limited in effectiveness, are available or being investigated in an attempt to control the disease long-term and with the aim of maintaining normal quality of life.

§ Traditional chemotherapy is generally ineffective, causes many side effects that may severely impair the patient's quality of life, and often does not prolong survival.

§ Intrahepatic arterial chemoembolization or chemoinfusion (TACE or TAC) has been adopted in the treatment of selected patients with unresectable lesions by the Stanford Multi-disciplinary Liver Tumor Clinic for the last four years. This treatment is not suitable for patients who already have signs of moderate liver failure and in patients with blockage of the portal vein. Long-term treatments with TACE or TAC have been associated with prolonged patient survival, and those who have good control or shrinkage of the tumor may even become suitable candidates for surgical resection or transplantation.

Liver Transplantation

Liver transplant is a treatment option for HCC that are surgically or medically unresectable, provided that the tumor is small (less than 5 cm or fewer than 4 lesions), confined to the liver, and without invasion into the blood vessels. More extensive tumors have a high risk for early recurrence and death after liver transplantation. After transplantation, the patient must receive either hepatitis B immunoglobulin (HBIG) or lamivudine, or both, to prevent HBV reinfection of the new liver.

Early diagnosis of small tumors is the only effective way of improving the outcome of liver cancer treatment, and that is only possible through screening of the high-risk population.

Liver Biopsy

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A liver biopsy is a procedure that involves taking a small piece of tissue from the liver to examine under the microscope. A liver biopsy is ordered to detect potential liver damage caused by chronic hepatitis B infections. The results of a biopsy can be used to help in making treatment decisions or evaluating current treatment.

A liver biopsy is considered a minor surgical procedure that is done in the hospital, but does not usually require admission (it's done as an "out-patient procedure"). From check-in to check-out, patients should expect to be in the hospital for approximately 6 - 8 hours. Although the procedure itself is relatively short, there is a longer recovery period where they will be asked to lie on their right side for several hours to prevent any bleeding. Be sure to tell patients to arrange for someone to drive them home upon discharge.

Methods of Liver Biopsy

Needle Biopsy
Most patients undergo this type of liver biopsy. This procedure involves numbing an area on the right ribcage, making a tiny incision, and then inserting a thin needle between the ribs to obtain a small tissue sample from the liver (a ½ inch sample is removed).

Laparoscopic Biopsy
This procedure is ordered when tissue samples from specific parts of the liver are required. A special tube called a "laparoscope" is inserted through a small incision in the abdomen. The laparoscope sends images of the liver to a monitor that a doctor watches to guide him or her in obtaining tissue samples from one or more parts of the liver.

Tran venous Biopsy
This procedure is used when patients have blood-clotting problems or fluid in the abdomen. It involves placing a biopsy needle inside a tube called a catheter, which is inserted into a vein in the neck and then guided into the liver to obtain a tissue sample

Evaluation of Liver Cancer

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Ultrasound of the liver and conventional CT scan are regularly obtained in the diagnostic evaluation of HCC (hepatocellular cancer or primary liver cancer), but they are often too insensitive to detect multi-focal small lesions and for treatment planning.

Thorough assessment with a biphasic spiral CT scan of the abdomen is essential. The fast spiral scanner allows scanning of the liver at the arterial phase shortly after the patient is given an intravenous bolus of contrast.

Percutaneous fine needle biopsy may be indicated in cases when the diagnosis of primary versus metastatic liver tumor is uncertain, providing that it can be safely performed. Post biopsy bleeding can be life threatening in cirrhotic patients with low platelet count, prolonged clotting time, and enlarged blood vessels that are under high pressure (portal hypertension). In general, metastatic liver lesions are rare in patients with cirrhosis. Screening for liver cancer is the only effective way of improving the outcome of treatment.

Liver Cancer Screening

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Symptoms

Liver cancer is a silent killer because the majority of the patients appear to be perfectly healthy and have no early signs or symptoms. Pain is uncommon until the tumor is quite large, and some large tumors don't even cause pain or other symptoms.

Later stages of liver cancer, when the cancer is very large or when it impairs the functions of the liver, can produce more obvious symptoms such as pain over the right upper abdomen, weight loss, lack of appetite, and finally the development of yellow discoloration of the eyes and skin (jaundice) and abdominal swelling.

Screening Frequency

Hepatitis B carriers who become infected early in childhood have a high risk of developing liver cancer whether they have cirrhosis or not. The risk is greater in men and those with a positive family history for liver cancer.

A reasonable approach to liver cancer screening includes:

§Alpha-fetoprotein (AFP) blood test every 6 months

§Liver Ultrasound at least once or twice a year

Either test alone, however, can miss the diagnosis. Once the patient develops cirrhosis, more frequent screening is generally recommended.

Hepatitis B and Primary Liver Cancer

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Chronic hepatitis B infections cause 80% of all primary liver cancer worldwide.

Patients with chronic hepatitis B infections are at increased risk for progressing to liver cancer or hepato cellular carcinoma (HCC), whether they develop cirrhosis or not.

In the U.S. the overall incidence of cancer is decreasing, except for primary liver cancer (as reported by the National Cancer Institute in 2005). This is due in large part to the increased number of Americans who are chronically infected with hepatitis B and hepatitis C. Although survival rates for most types of common cancers have improved over the years, the 5-year survival rate for liver cancer is still below 10%.

In the world, primary liver cancer is the 3^rd leading cause of death. According to the World Health Organization, at least 550,000 people die each year from primary liver cancer.

The hepatitis B vaccine was named the first "Anti-Cancer Vaccine" vaccine by the U.S. Food and Dug Administration since it prevents hepatitis B infections, the leading cause of primary liver cancer.

Who should be screened for liver cancer?

Early detection improves the chances of survival after treatment. Since liver cancer develops quietly, usually without symptoms, patients with chronic hepatitis B should undergo regular liver cancer screening. A reasonable approach is to begin regular liver cancer screening at 30 years of age (although experts are recommending starting an even earlier age since liver cancer can strike children, though rare).

It is important to stress that Asians and Asian Americans, who generally develop chronic hepatitis B infections soon at birth, have a high risk of developing liver cancer at an early age whether they have cirrhosis or not. The risk is greater in men and those with a positive family history for liver cancer.

What is liver cancer screening?

This generally consists of a simple blood test for alpha-fetoprotein (AFP) levels every 6 months and an ultrasound of the liver at least once a year. Either test alone can miss the diagnosis. Some doctors prefer CT scans to ultrasounds. Once the patient develops cirrhosis, or has a family history of liver cancer, more frequent screening is generally recommended.

What are the symptoms of liver cancer?

Liver cancer is a silent killer because the majority of patients appear to be perfectly healthy and have no early signs or symptoms. Both small and large tumors may be undetected due to the shielded location of the liver underneath the ribs.

Pain is uncommon until the tumor is quite large, and some large tumors don't even cause pain or any symptoms. Later stages of liver cancer, when the cancer is very large or when it impairs the functions of the liver, can produce more obvious symptoms such as abdominal pain, weight loss, lack of appetite, and finally the development of jaundice and abdominal swelling.

How is liver cancer treated?

Treatment of HCC is particularly challenging when compared with other types of cancer because in addition to the cancer itself, many patients have livers that have been damaged by chronic hepatitis B infections. For each individual patient, the potential benefits of the various treatment options must be balanced with the risk of liver failure and how it affects the patient's quality of life.

Surgical Treatment - When the tumor is small and the patient's liver condition is stable, surgical removal offers the best chance for long-term survival. Despite complete removal of the tumor, however, patients are still at risk for recurrent disease. They will need to be followed closely long-term, especially during the first year when the risk of recurrence is greatest.

Nonsurgical Treatment - For patients who cannot undergo surgery, a number of treatment options, though limited in effectiveness, are available or being investigated in an attempt to control the disease long-term and with the aim of maintaining normal quality of life. Traditional chemotherapy is generally ineffective, causes many side effects that may severely impair the patient's quality of life, and often does not prolong survival.

TACE (or TAC) - Since HCC are hypervascular tumors often fed by one or more blood vessels from the hepatic arteries, they present the unique opportunity to target the therapy directly into the tumor. Intrahepatic arterial chemoembolization or chemoinfusion (TACE or TAC) is used in the treatment of selected patients with tumors that cannot be surgically removed.

Long-term treatments with TACE or TAC have been associated with prolonged patient survival, and those who have good control or shrinkage of the tumor may even become suitable candidates for surgical resection or transplantation.

What about a liver transplant?

Liver transplant is the only treatment option for patients with liver cancer tumors that cannot be surgically or medically removed. The tumor must be small (less than 5 cm or fewer than 4 lesions), confined to the liver, and without invasion into the blood vessels. Larger or more extensive tumors have a high risk for early recurrence after liver transplantation.

What does the future hold?

Early diagnosis of small tumors is the only effective way of improving the outcome of liver cancer treatment, and that is only possible through screening of the high-risk population. Universal hepatitis B vaccination is ultimately the only hope for reducing the incidence of this frequently fatal cancer worldwide.

Children with Chronic Hepatitis B

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In general, the recommendations for children are the same as for adults - visits are typically every six months or once a year. Visits usually include a physical exam, HBV blood tests, AFP and LFT blood tests, and possible ultrasound imaging.

Adults with Chronic Hepatitis B

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Six-month visits are standard, but more frequent visits may be required for some patients. Visits usually include:

§Physical exam

§Blood tests for hepatitis B markers

§Blood tests for LFTs and AFP

§Ultrasound imaging of the liver

Diagnosis and Management of Hepatitis B

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High-Risk Groups

The hepatitis B virus can infect infants, children, teens and adults. Although everyone can be at some risk for a hepatitis B infection, there are people who are at greater risk because of their ethnic background, occupation, or lifestyle choices.

The following list is a guide for screening high-risk groups, but it certainly doesn't represent all potential risk factors.

§ Health care providers and emergency responders

§ Sexually active heterosexuals (more than 1 partner in the past six months)

§ Men who have sex with men

§ Individuals diagnosed with a sexually transmitted disease (STD)

§ Illicit drug users (injecting, inhaling, snorting, pill popping)

§ Sex contacts or close household members of an infected person

§ Children adopted from countries where hepatitis B is common (Asia, Africa, South America, Pacific Islands, Eastern Europe, and the Middle East)

§ Families of children adopted from the countries listed above

§ Individuals emigrating from countries where hepatitis B is common (see above)

§ Individuals born to parents who have emigrated from countries where hepatitis B is common (see above)

§ ALL pregnant women

§ Recipients of a blood transfusion before 1992

§ Kidney dialysis patients and those in early renal failure

§ Inmates of a correctional facility

§ Staff and clients of institutions for the developmentally disabled

§ Any individual who may have other risk factors not included on this list

Blood Tests

Be sure to carefully discuss your blood test results with your health care provider. Understanding your hepatitis B blood test results can be confusing, so you want to be clear about your diagnosis - do you have a new infection, have you recovered from a past infection, or do you have a chronic infection?

You may want to take a copy of this information with you to your appointment to use as a reference guide. In addition, it is helpful if you request a written copy of your blood tests so that you fully understand which test is positive or negative.

To understand your tests, you will need to understand two basic medical terms:

§Antigen -a foreign substance in the body, such as the hepatitis B virus.

§Antibody -a protein that your immune system makes in response to a foreign substance. Antibodies can be produced in response to a vaccine or a natural infection. Antibodies usually protect you from future infection.

Common Hepatitis B Blood Tests

§HBsAg (hepatitis B surface antigen) - This refers to the outer surface of the hepatitis B virus that triggers an antibody response. A "positive" or "reactive" HBsAg test result means that the person is infected with the hepatitis B virus. This can be an "acute" or a "chronic" infection. Infected people can pass the virus on to others through their blood.

§HBsAb or anti-HBs (hepatitis B surface antibody) - This refers to the protective antibody that is produced in response to an infection. It appears when a person has recovered from an acute infection and cleared the virus (usually within six months) or responded successfully to the hepatitis B vaccine shots. A "positive" or "reactive" HBsAb (or anti-HBs) test result indicates that a person is "immune" to any future hepatitis B infection and is no longer contagious. This test is not routinely included in blood bank screenings.

§HBcAb or anti-HBc (hepatitis B core antibody) - This refers to an antibody that is produced in response to the core-antigen, a component of the hepatitis B virus. However, this is not a protective antibody. In fact, it is usually present in those chronically infected with hepatitis B. A "positive" or "reactive" HBcAb (or anti-HBc) test result indicates a past or present infection, but it could also be a false positive. The interpretation of this test result depends on the first two test results. Its appearance with the protective surface antibody (positive HBsAb or anti-HBs) indicates prior infection and recovery. For chronically infected persons, it will usually appear with the virus (positive HbsAg).

Hepatitis B Blood Tests: FAQ

Is there a blood test for hepatitis B?

There is a simple hepatitis B blood test that your doctor or health clinic can order called the “hepatitis B blood panel”. This blood sample can be taken in the doctor’s office. There are 3 common tests that make up this blood panel. Sometimes the doctor may ask to check your blood again six months after your first visit to confirm your hepatitis B status. If you think you have been recently infected with hepatitis B, it will take 4 -6 weeks before the virus will be detected in your blood.

Understanding your hepatitis B blood test results can be confusing, so you want to be clear about your diagnosis - do you have a new infection, have you recovered from a past infection, or do you have a chronic infection? In addition, it is helpful if you request a written copy of your blood tests so that you fully understand which tests are positive or negative.

What three tests make up the "hepatitis B blood panel"?

The hepatitis B blood panel requires only one blood sample but includes three tests:

§HBsAg (hepatitis B surface antigen)

§HBsAb or Anti-HBs (hepatitis B surface antibody)

§HBcAb or anti-HBc (hepatitis B core antibody)

The doctor needs all 3 blood test results in order to determine your diagnosis.

What is the hepatitis B surface antigen (HBsAg)?

These tests for the presence of virus. A "positive" or "reactive" HBsAg test result means that the person is infected with the hepatitis B virus, which can be an "acute" or a "chronic" infection. Infected people can pass the virus on to others through their blood and infected bodily fluids.

What is the hepatitis B surface antibody (HBsAb oranti-HBs)?

A "positive" or "reactive" HBsAb (or anti-HBs) test result indicates that a person has successfully responded to the hepatitis B vaccine or has recovered from an acute hepatitis B infection. This result means that you are immune to future hepatitis B infection and you are not contagious. This test is not routinely included in blood bank screenings.

What is the hepatitis B core antibody (HBcAb)?

The HBcAb is an antibody that is part of the virus- it does not provide protection. A "positive" or "reactive" HBcAb (or anti-HBc) test result indicates a past or present infection, but it could also be a false positive. The interpretation of this test result depends on the results of the other two tests. Its appearance with the protective surface antibody (positive HBsAb or anti-HBs) indicates prior infection and recovery. For chronically infected persons, it will usually appear with the virus (positive HBsAg).

I donated blood and received a letter about hepatitis B from the blood bank, what does it mean?

First, do not panic. The letter does not necessarily mean that you are infected with hepatitis B. All donated blood is screened for hepatitis B. Many blood banks use the "hepatitis B core antibody" test to screen donor blood for potential hepatitis B infection (see “What is the hepatitis B core antibody?” above). This test can detect whether a person might have been exposed to the hepatitis B virus, but by itself this blood test doesn't tell whether the person is actually infected or not. This is why it is very important to see your doctor so that he can order the hepatitis B blood panel to make an accurate diagnosis.

Understanding the Results of Your Blood Tests

The interpretation of each individual's results should receive expert evaluation. Unusual results do occur and the chart below is simply an "average" representing the most likely interpretation. It is not intended as personal medical advice. All individuals are strongly encouraged to consult their own health care provider to evaluate their blood test results.

Tests	Results	Interpretation	Recommendation
HBsAg	negative	Not immune - has not been infected, but is still at risk for possible future infection. Needs protection.	Get the vaccine.
HBsAb (anti-HBs)	negative
HBcAb (anti-HBc)	negative
HBsAg	negative	Immune - surface antibodies present. You may have been already vaccinated, or you have recovered from a prior hepatitis B infection. You cannot infect others.	The vaccine is not needed.
HBsAb (anti-HBs)	positive
HBcAb (anti-HBc)	negative or positive
HBsAg	positive	New infection or a chronic infection - positive surface antigen, which means hepatitis B virus is present. You can spread the virus to others.	Find a doctor who is knowledgeable about hepatitis B for further evaluation.
HBsAb (anti-HBs)	negative
HBcAb (anti-HBc)	negative or positive
HBsAg	negative	*Unclear- Several different interpretations are possible. You may need to have these tests repeated. See below.	The vaccine may or may not be needed. Find a doctor who is knowledgeable about hepatitis B for further evaluation.
HBsAb (anti-HBs)	negative
HBcAb (anti-HBc)*	positive

*Positive Hepatitis B Core-Antibody Test Result (HBcAB+)

1. May be recovering from acute hepatitis B infection
2. May be distantly immune and test is not sensitive enough to detect low level of HBsAb (or anti-HBs) in serum
3. May be susceptible with a false positive HBcAb or anti-HBc
4. May be undetectable level of HBsAg present in the serum and the person is actually chronically infected

Additional Blood Tests

HBeAg (Hepatitis B e-Antigen) - This is a viral protein that is secreted by hepatitis B infected cells. It is associated with chronic hepatitis B infections and is used as a marker of active viral disease and a patient's degree of infectiousness.

§A positive result indicates the person has high levels of virus and greater infectiousness.

§A negative result indicates low to zero levels of virus in the blood and a person is considered non infectious. This test is often used to monitor the effectiveness of some hepatitis B therapies, whose goal is to convert a chronically infected individual to "e-antigen negative".

The absence of e-antigen, however, does not necessarily exclude active viral replication. Some patient groups have mutant viruses that do not give rise to e-antigen. Patients with negative e-antigen, but detectable viral DNA, are traditionally thought to be more resistant to conventional treatment than those who have positive e-antigen levels.

HBeAb or anti-HBe (Hepatitis B e-Antibody) - This antibody is made in response to the e-antigen and is detected in patients who have recovered from hepatitis B infections as well as those who are chronically infected. Chronically infected individuals who stop producing e-antigen sometimes produce e-antibodies. The clinical significance of this result is unclear but it is generally considered to be a good thing. In rare cases, anti-HBe may be associated with active viral replication in patients with e-antigen negative virus mutations.

Liver Function Tests (or Liver Enzymes) - Includes blood tests that assess the general health of the liver. When elevated above normal values, the ALT (alanine aminotransferase) and AST (aspartate aminotransferase) tests indicate liver damage. They are enzymes located in liver cells that can leak out into the bloodstream when liver cells are injured.

§ ALT (alanine aminotransferase) is the liver enzyme marker that is followed most closely in those chronically infected with hepatitis B. This test is useful in deciding whether a patient would benefit from treatment, or for evaluating how well s/he is responding to therapy.

AFP (Alpha-FetoProtein) - This is a normal protein produced in the developing fetus. Pregnant women will have elevated AFP's. Other adults, however, should not have elevated AFP in their blood. This test is used as a liver tumor marker for patients with chronic hepatitis B. Patients should have their AFP levels monitored routinely since high levels could indicate the possibility of liver cancer.

Ferritin - Iron is stored in the liver in the form of ferritin. Increased levels of ferritin means a high level of iron is being stored. This could result from an increased iron intake in the diet (vitamin supplements, food cooked in iron pots, etc.), but it can also occur from a destruction of liver cells causing leakage of ferritin. More research is needed to understand the relationship between elevated ferritin and liver cancer.

A Guide to Common Blood Tests

Hepatitis B Basics and Beyond, Bristol-Myers Squibb Company Issue No. 2, October 2003

Test	Normal Range	Abnormal Range Mile-Moderate	Abnormal Range Severe
Liver Enzymes
Aspartate aminotransferase (AST)	<40 IU/L	40-200 IU/L	>200 IU/lL
Alanine aminotransferase (ALT)	<40 IU/L	40-200 IU/L	>200 IU/L
Gamma-glutamyl transferase (GGT)	<60 IU/L	60-200 IU/L	>200 IU/L
Alkaline phosphatase	<112 IU/L	112-300 IU/L	>300 IU/L
Liver Function Tests
Bilirubin	<1.2 mg/dL	1.2-2.5 mg/dL	>2.5 mg/dL
Albumin	3.5-4.5 g/dL	3.0-3.5 g/dL	<3.0 g/dL
Prothrombin time	<14 seconds	14-17 seconds	>17 seconds
Blood Count
White blood count (WBC)	>6000	3000-6000	<3000
Hematocrit (HCT)	>40	35-40	<35
Platelets	>150,000	100,000-150,000	<100,000
*Key*
*U= International Unit*	*L=liter*	*dL=deciliter*	*mg=milligrams*

Positive HBV Tests

An acute hepatitis B infection follows a relatively long incubation period - from 1 to 4 months. It can take up to six months, however, for a person's serology to reflect whether they have recovered from an acute infection or have become chronically infected.

The following graphic from the Centers for Disease Control and Prevention (CDC) represents the typical course of an acute hepatitis B infection.

CDC Notes About HBV Infections

Serologic markers of HBV infection vary depending on whether the infection is acute or chronic.

§HBsAg is the first serologic marker to appear following acute infection, which can be detected as early as 1 or 2 weeks and as late as 11 or 12 weeks (mode, 30-60 days) after exposure to HBV.

§HBsAg is no longer detectable in serum after an average period of about 3 months in persons who have recovered.

§HBeAg is generally detectable in patients with acute infection; the presence of HBeAg in serum correlates with higher titers of HBV and greater infectivity.

§ A diagnosis of acute HBV infection can be made on the basis of the detection of IgM anti-HBc in serum; IgM anti-HBc is generally detectable at the time of clinical onset and declines to sub-detectable levels within 6 months.

§IgG anti-HBc persists indefinitely as a marker of past infection.

§HBsAb (or Anti-HBs) becomes detectable during convalescence after the disappearance of HBsAg in patients who do not progress to chronic infection. The presence of anti-HBs following acute infection generally indicates recovery and immunity from re-infection.

All patients with chronic hepatitis B infections, including children and adults, should be monitored regularly since they are at increased risk for developing cirrhosis, liver failure, or liver cancer.

Early intervention with the current treatments may benefit patients with signs of active liver disease. Screening and vaccination of family members is also recommended.

Donating Blood

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If you are a blood donor, you may receive blood collection agency notifying you that you may be infected with hepatitis B.

First, do not panic. The letter does not necessarily mean that you are infected with hepatitis B.

All donated blood is screened for hepatitis B, as well as other blood-borne viruses such as HIV and hepatitis C. Many blood banks use the "hepatitis B core antibody" test to screen donor blood for potential hepatitis B infection. This test can detect whether a person might have been exposed to the hepatitis B virus, but by itself this blood test doesn't tell whether the person is actually infected or not. This is why it is very important to see your doctor for additional hepatitis B blood tests.

Further Blood Tests Are Needed

If the blood bank tells you that the "hepatitis B core antibody" test was positive, you could be:

§ chronically infected with hepatitis B;

§ recovering from an infection;

§ already recovered from a past infection;

§ the result could be a false positive.

You won't know without further blood tests. This is why it is so important that you see your doctor for follow-up hepatitis B testing.

Liver & Its Functions

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The liver is such an important organ that we can survive only one or two days if it shuts down - if the liver fails, your body will fail, too. Fortunately, the liver can function even when up to 75% of it is diseased or removed. This is because it has the amazing ability to create new liver tissue (i.e. it can regenerate itself) from healthy liver cells that still exist.

If your body were an automobile, your liver would be considered the engine. It does hundreds of vital things to make sure everything runs smoothly:

§ Stores vitamins, sugar and iron to help give your body energy.

§ Controls the production and removal of cholesterol.

§ Clears your blood of waste products, drugs and other poisonous substances.

§ Makes clotting factors to stop excessive bleeding after cuts or injuries.

§ Produces immune factors and removes bacteria from the bloodstream to combat infection.

§ Releases a substance called "bile" to help digest food and absorb important nutrients.

N.B: Click on images for large view

Hepatitis B/Hepatitis D

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Hepatitis D Co-Infection

Hepatitis D is a type of viral hepatitis caused by the hepatitis D virus (HDV), which needs the hepatitis B virus to exist. Only people who are already infected with hepatitis B can be infected with hepatitis D.

HDV Co-infection - occurs simultaneously when first infected with the hepatitis B virus.

HDV Super-infection – occurs in persons with an existing chronic hepatitis B infection.

HDV-HBV Co-infection

A co-infection may result in a more severe acute disease and a higher risk (2%-20%) of developing acute liver failure compared with those infected with HBV alone.

^{HDV-HBV Super-infection}

Chronic HBV carriers who acquire HDV super-infections usually develop chronic HDV infection as well. Progression to cirrhosis is believed to be more common with HDV-HBV chronic infections.

Transmission - hepatitis D is spread the same way as hepatitis B:

§Contact with infected blood

§Unprotected sex

§Exposure to dirty needles (i.e. needle sticks, sharing drugs, tattoo parlors, body piercings).

§From an infected woman to her newborn during birth

Prevention – the only way to prevent a HDV infection is to prevent a hepatitis B infection!

Get the hepatitis B vaccine and reduce your risk.

Treatment and Management – there is really no effective treatment for HDV. For an acute HDV infection, only supportive care for symptoms can be provided. For a chronic HDV infection, some doctors may try interferon-alpha, but this may only slow disease progression. Ultimately, a liver transplant may be required.

HBV/HIV Co-infection

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A person who is infected with both the hepatitis B and the HIV viruses is said to have a HBV/HIV Co-infection. Approximately 10% of the HIV-infected population worldwide is infected with hepatitis B. This figure may approach 20% in Southeast Asia, and 5% in North America and Western Europe. Since both the hepatitis B virus and the HIV virus share similar transmission routes, it is not surprising that there is a high frequency of co-infection. Sexual activity and/or injection drug use are the most common routes of transmission of the hepatitis B virus among those also infected with HIV.

While highly active antiretroviral therapy (HAART) has dramatically improved the lives of those with HIV, the consequences of associated illnesses such as hepatitis B co-infections have become more relevant.

Conditions associated with hepatitis B and C are currently among the leading causes of hospital admission and death in the HIV-infected population. Therefore, the adequate management of hepatitis B and C is now being considered a priority in HIV-confected patients.

Since there is not a ‘cure’ at this time for hepatitis B, the main goal of treating HBV/HIV-co-infection is to stop or slow down HBV viral activity as much as possible and for as long as possible.

Diagnosis and Screening

All HIV-positive patients should be screened for viral hepatitis (A, B and C). Those who test positive for hepatitis B and C should seek care from a liver specialist (herpetologist or gastroenterologist) for further evaluation and management.

HBV/HIV co-infected patients who are not immune to the hepatitis A virus (lacking anti-HAV IgG antibodies) should be vaccinated to protect them from acquiring another harmful liver virus.

Management and Treatment

There are two main reasons for considering HBV therapy as a priority in HBV/HIV co-infected patients:

§First, liver disease may progress more rapidly in those patients co-infected with HBV/HIV and could lead to serious liver disease complications such as cirrhosis and liver cancer at younger ages.

§Second, there is a higher risk of developing hepatotoxicity following the initiation of antiretroviral therapy in HIV patients co-infected with HBV than in patients infected with HIV alone.

In patients infected with HBV, HIV can lead to higher rates of chronicity, decreased rates of anti-HBe and anti-HBs seroconversion, and increased viral replication, probably due to the impairment of the body’s immune responses. As a consequence, HBV/HIV co-infection is associated with increased liver fibrosis progression and increased rate of liver decompensation, cirrhosis, liver cancer or liver failure. Therefore, it is recommended to avoid the development of severe immune deficiency (defined as <200 CD4 cells/mm 3) in HBV/HIV co-infected persons.

There is no evidence that HBV affects HIV disease progression or that HBV alters the response of HIV to antiretroviral therapy (ART). However, starting ART may be associated with an increased risk of liver inflammation in co-infected individuals, as evidenced by ALT ( Alanine Aminotransferase) flares or rising liver enzymes. This may reflect both an immune response against HBV and/or drug toxicity.

Five drugs have been approved so far for the treatment of chronic hepatitis B:

§Interferon-alpha (Intron A) is given by injection several times a week for six months to a year, or sometimes longer. The drug can cause side effects such as flu-like symptoms, depression, and headaches. Approved in 1991 and available for both children and adults.

§Pegylated Interferon (Pegasys) is given by injection once a week usually for six months to a year. The drug can cause side effects such as flu-like symptoms, depression and other mental health problems. Approved May 2005 and available only for adults.

§ Lamivudine (Epivir-HBV, Zeffix, or Heptodin) is a pill that is taken once a day, with almost no side effects, for at least one year or longer. A primary concern is the possible development of hepatitis B virus mutants during and after treatment. Approved in 1998 and available for both children and adults.

§ Adefovir dipivoxil (Hepsera) is a pill taken once a day, with few side effects, for at least one year or longer. The primary concern is that kidney problems can occur while taking the drug. Approved September 2002 and available only for adults. Pediatric clinical trials are being planned.

§ Entecavir (Baraclude) is a pill taken once a day, with almost no side effects for up to one year. It is considered the most potent oral antiviral drug for chronic hepatitis B to date. Approved April 2005 and available only for adults. Pediatric clinical trials may be planned for the future.

Other drugs with anti-HBV activity such as tenofovir and emtricitabine are FDA approved for treatment of HIV infection and are frequently used in coinfected patients as anti-HBV agents.

The decision to treat chronic hepatitis B and the choice of drugs is controversial and likely to vary in different situations. Treatment recommendations include four main variables that should guide the selection of patients to be treated for HBV and of the drug of choice:

§Transaminase levels (ALT, AST)

§HBV DNA viral loads

§HBV e-Antigen presence (HBeAg)

§Liver fibrosis staging (liver biopsy)

§Ultrasound of the liver

Acute vs. Chronic Hepatitis B

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When a person is first infected with the hepatitis B virus, this is called an "acute infection". A person may not have any symptoms or s/he could become seriously ill. Most adults will recover and get rid of the virus without any problems. If the virus remains in the blood for more than six months, then a person is diagnosed as having a "chronic infection".

Fortunately, most healthy adults (90%) who are infected with the hepatitis B virus will recover and develop protective antibodies against future hepatitis B infections.

Unfortunately, this is not true for infants and young children — 90% of infants and up to 50% of young children infected with hepatitis B will not get rid of the virus and will develop a chronic infection. A smaller number of infected adults (5-10%) will also become chronically infected with hepatitis B.

A simple blood test can diagnose a hepatitis B infection. Repeated blood tests may be ordered over a six-month period to make an accurate diagnosis.

N.B: Click on images for large view

Symptoms of Hepatitis B

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Hepatitis B is called a "silent infection" because most people do not have noticeable symptoms when they are first infected. When a healthy adult is infected with the hepatitis B virus, their body can respond in different ways. People who do not know they are infected can unknowingly pass the virus to others.

§Hepatitis B causes no symptoms in about 69 percent of infected people.

§Approximately 30 percent of infected individuals will have some symptoms. Many will think they just have the flu and ignore the symptoms.

§About 1 percent of those infected will develop life threatening, "fulminates hepatitis". These people may go into liver failure and require immediate medical attention. Although this response is rare, fulminate hepatitis develops suddenly and can be fatal if left untreated.

Common symptoms of hepatitis B infection include:

§Fever, fatigue, muscle or joint pain

§Loss of appetite

§Mild nausea and vomiting

Serious symptoms that require immediate medical attention and maybe even hospitalization:

§Severe nausea and vomiting

§Yellow eyes and skin ("jaundice")

§Bloated or swollen stomach

It is always a good idea to talk to your doctor if you don't feel well or if you are uncertain about whether you have been infected with hepatitis B. A simple blood test can easily diagnose a hepatitis B infection.

High Risk Groups of Hepatitis B

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§ Health care workers and emergency personnel
§ Infants born to mothers who are infected at the time of delivery

§ Partners or individuals living in close household contact with an infected person

§ Individuals with multiple sex partners, past or present

§ Individuals who have been diagnosed with a sexually transmitted disease

§ Illicit drug users (injecting, inhaling, snorting, popping pills)

§ Men who have sex with men

§ Individuals who received a blood transfusion prior to 1992

§ Individuals who get tattoos or body piercing

§ Individuals who travel to countries where hepatitis B is common (Asia, Africa, South America, the Pacific Islands, Eastern Europe, and the Middle East)

§ Families adopting children from countries where hepatitis B is common

§ Individuals emigrating from countries where hepatitis B is common, or born to parents who emigrated from these countries

§ Individuals with early kidney disease or undergoing kidney dialysis

§ Individuals who use blood products for medical conditions (i.e. hemophilia)

§Residents and staff of correctional facilities and group homes

Transmission of Hepatitis B

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Hepatitis B is transmitted through blood and infected bodily fluids. This can occur through:

§ direct blood-to-blood contact

§ unprotected sex

§ unsterile needles

§ from an infected woman to her newborn during the delivery process.

Other possible routes of infection include sharing sharp instruments such as razors, toothbrushes or earrings. Body piercing, tattooing and acupuncture are also possible routes of infection unless sterile needles are used. Hepatitis B is NOT transmitted casually. It cannot be spread through sneezing, coughing, hugging or eating food prepared by someone who is infected with hepatitis B. Everyone is at some risk for a hepatitis B infection, but some groups are at higher risk because of their occupation or life choices.

Statistics of Hepatitis B

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Most healthy adults (90%) who are infected will recover and develop protective antibodies against future hepatitis B infections. A small number (5-10%) will be unable to get rid of the virus and will develop chronic infections. Unfortunately, this is not true for infants and young children – 90% of infants and up to 50% of young children infected with hepatitis B will develop chronic infections. Therefore, vaccination is essential to protect infants and children.

Hepatitis B is 100 times more infectious than the AIDS virus, yet it can be prevented with a safe and effective vaccine. For the 400 million people worldwide who are already chronically infected with hepatitis B, the vaccine is of no use. The future, however, is much brighter with the current advances in drug development and treatment options.

Hepatitis B In the World

§ 2 billion people have been infected (1 out of 3 people).

§ 400 million people are chronically infected.

§ 10-30 million will become infected each year.

§ An estimated 1 million people die each year from hepatitis B and its complications.

§ Approximately 2 people die each minute from hepatitis B.

N.B: Click on images for large view

Hepatitis B In the United States

§ 12 million Americans have been infected (1 out of 20 people).

§ More than one million people are chronically infected.

§ Up to 100,000 new people will become infected each year.

§ 5,000 people will die each year from hepatitis B and its complications.

§ Approximately 1 health care worker dies each day from hepatitis B.

Hepatitis B In Bangladesh

Not very well studied. Several studies found huge number of patients and carriers. It is estimated that 7-9 per cent of our population may be suffering from the disease or carrying the virus. This is a great cause of concern.

About Hepatitis B

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Hepatitis B is the most common serious liver infection in the world. The hepatitis B virus that attacks the liver causes it. The virus is transmitted through blood and infected bodily fluids. This can occur through direct blood-to-blood contact, unprotected sex, use of unsterile needles, and from an infected woman to her newborn during the delivery process.

The good news is that there is a simple blood test to find out if you have been infected. There is also a safe and effective vaccine to protect you and your loved ones against hepatitis B. Finally, there are promising new treatments available for those who have developed chronic hepatitis B infections.

Hepatitis B Virus

Electron microscopic image of hepatitis B virus particles

Transmission electron micrograph (TEM) revealed the presence of hepatitis B

Viral Hepatitis

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Viral hepatitis refers to infections caused by viruses that directly attack the liver. Chronic cases of viral hepatitis can lead to life-threatening liver cirrhosis (or scarring), liver failure and liver cancer. The most common forms of viral hepatitis are hepatitis A, hepatitis B, hepatitis C, and hepatitis D.

Type of Viral Hepatitis	Mode of Transmission / Prevention
Hepatitis A (HAV)	Contaminated food and water. There is a safe HAV vaccine.
Hepatitis B (HBV)	Infected blood, sex, and needles. From an infected mother to her newborn. There is a safe HBV vaccine.
Hepatitis C (HCV)	Infected blood and needles. There is no vaccine.
Hepatitis D (HDV)	Must already have hepatitis B. Infected blood, sex, and needles. From an infected mother to her newborn. Get the hepatitis B vaccine.
Hepatitis E (HEV)	Contaminated water. There is no vaccine.

Photo: Viral Hepatitis