Ian Quill : My World

Leisure, A Poem by W. H. Davies

2015-06-10T22:16:00.000+01:00

Leisure

What is this life if, full of care,

We have no time to stand and stare.

No time to stand beneath the boughs

And stare as long as sheep or cows.

No time to see, when woods we pass,

Where squirrels hide their nuts in grass.

No time to see, in broad daylight,

Streams full of stars, like skies at night.

No time to turn at Beauty's glance,

And watch her feet, how they can dance.

No time to wait till her mouth can

Enrich that smile her eyes began.

A poor life this if, full of care,

We have no time to stand and stare.

A Poem by W. H. Davies,

"Leisure" is a poem by Welsh poet W. H. Davies, appearing originally in his Songs Of Joy and Others, published in 1911 by A. C. Fifield and then in Davies' first anthology Collected Poems, by the same publisher in 1916. – via Wikipedia

Cranky Old Man

2012-12-20T07:40:00.000+00:00

Cranky Old Man...

When an old man died in the geriatric ward of a nursing home in an Australian country town, it was believed that he had nothing left of any value.

Later, when the nurses were going through his meagre possessions, they found this poem. Its quality and content so impressed the staff that copies were made and distributed to every nurse in the hospital.

One nurse took her copy to Melbourne. The old man's sole bequest to posterity has since appeared in the Christmas editions of magazines around the country and appearing in mags for Mental Health. A slide presentation has also been made based on his simple, but eloquent, poem.

And this old man, with nothing left to give to the world, is now the author of this 'anonymous' poem winging across the Internet.

Cranky Old Man

What do you see nurses? . . .. . .What do you see?
What are you thinking .. . when you're looking at me?
A cranky old man, . . . . . .not very wise,
Uncertain of habit .. . . . . . . .. with faraway eyes?
Who dribbles his food .. . ... . . and makes no reply.
When you say in a loud voice . .'I do wish you'd try!'
Who seems not to notice . . .the things that you do.
And forever is losing . . . . . .. . . A sock or shoe?
Who, resisting or not . . . ... lets you do as you will,
With bathing and feeding . . . .The long day to fill?
Is that what you're thinking?. .Is that what you see?
Then open your eyes, nurse .you're not looking at me.
I'll tell you who I am . . . . .. As I sit here so still,
As I do at your bidding, .. . . . as I eat at your will.
I'm a small child of Ten . .with a father and mother,
Brothers and sisters .. . . .. . who love one another
A young boy of Sixteen . . . .. with wings on his feet
Dreaming that soon now . . .. . . a lover he'll meet.
A groom soon at Twenty . . . ..my heart gives a leap.
Remembering, the vows .. .. .that I promised to keep.
At Twenty-Five, now . . . . .I have young of my own.
Who need me to guide . . . And a secure happy home.
A man of Thirty . .. . . . . My young now grown fast,
Bound to each other . . .. With ties that should last.
At Forty, my young sons .. .have grown and are gone,
But my woman is beside me . . to see I don't mourn.
At Fifty, once more, .. ...Babies play 'round my knee,
Again, we know children . . . . My loved one and me.
Dark days are upon me . . . . My wife is now dead.
I look at the future ... . . . . I shudder with dread.
For my young are all rearing .. . . young of their own.
And I think of the years . . . And the love that I've known.
I'm now an old man . . . . . . .. and nature is cruel.
It's jest to make old age . . . . . . . look like a fool.
The body, it crumbles .. .. . grace and vigour, depart.
There is now a stone . . . where I once had a heart.
But inside this old carcass . A young man still dwells,
And now and again . . . . . my battered heart swells
I remember the joys . . . . .. . I remember the pain.
And I'm loving and living . . . . . . . life over again.
I think of the years, all too few . . .. gone too fast.
And accept the stark fact . . . that nothing can last.
So open your eyes, people .. . . . .. . . open and see.
Not a cranky old man .
Look closer . . . . see .. .. . .. .... . ME!!

Remember this poem when you next meet an older person who you might brush aside without looking at the young soul within. We will all, one day, be there, too!

With thanks to: J.J. Cohen

What if Money didn't matter?

2012-11-23T14:16:00.000+00:00

Margaret’s Story

2012-11-14T14:02:00.000+00:00

Margaret’s Story

Hi folks, here is a story from a good freind of mine and I would appreciate it if you could read and click on the links to sign our petition, thank-you.... Ian

This is my story…how I got to be here…and why I started the campaign at Change.org.

My name is Margaret Dudley, I am 61 years old and live in the great city of San Antonio, Texas. I have a wonderful, supportive husband and we have three daughters and six beautiful grandchildren.

Remember when cosmetic tattoos were first becoming popular? Permanent lip liner and eyebrows were all the rage. Many of my girlfriends and I had these procedures done and the results were great. It was nothing extreme… just a little subtle enhancement. We are ‘baby boomers’ and quite honestly not ready to look like our mothers. I looked and felt great…for a while.

I had not felt well in the years following my cosmetic “tattooing” procedure, and my doctors attributed my many symptoms to just getting older and said it was likely the onset of menopause.

I was really exhausted and fatigued all the time, and was often nauseated and bloated. I began to experience other stomach problems as well as crippling back pain. The worst of it was an awful four-year long ordeal with skin problems on the palms of both hands… severe cracks, bleeding, and extreme itching. I became very depressed as doctors continued to misdiagnose my symptoms for eleven years.

One day, a proverbial light came on and I told my doctor about a lady who had this procedure done at the same place that my friends and I did and she was diagnosed with the Hepatitis C virus (HCV) after she donated blood(More).My doctor immediately ran the test and the very next day (September 9th, 2011) I received the devastating news that I, too, was infected with this disease.

I immediately began researching and learning everything I could about this disease, trying to learn what was in store for me, what treatment was available, and most importantly, if there was a CURE!

Then I found the best news…

I learned there was indeed a cure for this awful virus that was now growing rampantly in my body. This cure consisted of two drugs, GS-7977 (now called sofosbuvir) and daclatasvir. When combined in Phase II trials this combination cured 100% of the most prevalent type of Hepatitis C.

And this treatment had minimal or no side effects!

The two drugs with this amazing success rate are owned by Gilead Sciences and Bristol-Myers Squibb. I was actually scheduled to be in this very trial which was being conducted by my hepatologist and leading HCV researcher, Dr. Eric Lawitz who heads Alamo Medical Research Center here in San Antonio; but due to a delay in my liver biopsy I missed the trial by mere weeks. Dr. Lawitz assured me once the results were released in April 2012 the two drug companies who owned these two successful and miraculous drugs would enter immediately into Phase III trials and this life-saving combo would soon be available for me and the countless millions of others who are suffering and dying with this disease.

There were many news articles on Fox News and other media outlets discussing the progress and amazing success of these trials. My family and I were so confident that these Phase III trials would soon be underway. My youngest daughter even postponed her wedding by six months knowing by then I would be cured. (Kim was married this past September 29th)

Then all of a sudden it was abruptly announced by Gilead Sciences that there would be no Phase III trials, with no conceivable or plausible explanation as to why! This felt even more devastating than my initial diagnosis, if that is possible!

Seeing that my life and millions of others now hang in the balance, I launched a petition at Change.org urging Gilead Sciences to make this life-saving medication available for the millions of HCV sufferers as well as for myself. Although it feels much like a David vs. Goliath battle trying to get Gilead Sciences to reconsider their position I have now become an advocate for this cause and have formed a grassroots effort, HCV Coalition for The Cure. I want to bring the nation’s attention to this dire situation.

I have heard thousands of heartbreaking stories from people who need this cure and they need it NOW! I am asking you to sign this petition because everyone is affected by Hepatitis C, either fighting it, or knows a family or friend who is.

“Individually, we are one drop. Together, we are an ocean.” -Ryunosuke Satoro

Your signature could be the drop that creates this ocean! And it may be the very one needed to get this cure for millions.

Sincerely,

Margaret Dudley.

Gilead Sciences: Please collaborate with Bristol Myers for the Cure for Hepatitis C NOW!

2012-09-16T08:39:00.003+01:00

Please read and then click here to sign this petition to Gilead Sciences, organised by Margret Dudley via Change.org -

"Because patients should be first and foremost. This disease is now killing more then HIV"

Dear Gilead Sciences

Over 170 million Hepatitis C Virus sufferers and their families were ecstatic when you released the data at the past European Association for the Study of the Liver (EASL) conference about the spectacular results achieved with the drug combination of your GS-7977 and Bristol-Myers’ daclatasvir.

It was nothing short of amazing, a 100% cure rate in genotype 1 patients and 91% in genotypes 2 & 3 without the utilization of Interferon or Ribavirin. Our prayers were finally answered, or so it seemed. Then, to our utter dismay and puzzlement, Gilead Sciences elected not to take these drugs into Phase III trials!

If recouping the investment of $11 billion and making profits are at the forefront of Gilead’s considerations, it would seem that expediting these drugs to market would be the paramount concern. If Gilead Sciences is determined to move ahead without Bristol Myers Squibb’s Daclatasvir and elects to pursue drug trials with GS-7977 + Ribavirin (along with its dreadful side effects) or GS-7977 + GS-5885, then it is a shame that the published results of the drug combination of GS-7977 and Bristol-Myers’ Daclatasvir has brought false hopes to over 170 million HCV sufferers and summarily, left us in a state of despair!

What is to be achieved in future trials with other drugs? How can Gilead Sciences abandon a proven drug combination that has 100% cure rate, with minimal side effects (headaches, fatigue, and nausea)? These are results that are going to be hard to top.

It is estimated that currently only 3% of the HCV population elects to undergo treatment because of the dreadful side effects of Interferon & Ribavirin. Please factor into your considerations that nearly 100% of HCV patients would undergo treatment if these drugs were made available.

If Gilead Sciences delays moving ahead with the efficacious GS-7977 and Bristol-Myers’ daclatasvir trial-proven drug combination, how many more people will advance to cirrhosis and/or liver cancer, how many more will require a liver transplant, and how many more lives will be lost?

Click here to sign this petition, Thank you... Ian

Valuable Lesson from Bill Gates

2012-08-14T01:08:00.000+01:00

Hi folks, sorry it's been a while!!! Recovery is ongoing but going well and I WILL get round to posting about life 'post-treatment'. I get final results in Feb 2013 but currently I'm HCV NEGATIVE and feel fantastic!!!

In the meantime, I saw this which caught my eye and thought I'd share it. It's a speech written by the great Bill Gates, founder of Microsoft and a wonderful humanitarian. It was a speech he gave to an American high school and I love it.

Speaking as someone who has ridden the' roller-coaster of life' and a parent, I thought it poignant and held some valuable lessons that I could pass on. Enjoy...

Rule 1 : Life is not fair - get used to it!

Rule 2 : The world doesn't care about your self-esteem.
The world will expect you to accomplish something
BEFORE you feel good about yourself.

Rule 3 : You will NOT make $60,000 a year right out of high school.
You won't be a vice-president with a car phone until you earn both.

Rule 4 : If you think your teacher is tough, wait till you get a boss

Rule 5 : Flipping burgers is not beneath your dignity.
Your Grandparents had a different word for burger flipping:
They called it opportunity.

Rule 6 : If you mess up, it's not your parents' fault,
so don't whine about your mistakes, learn from them.

Rule 7 : Before you were born, your parents weren't as boring
as they are now. They got that way from paying your bills,
cleaning your clothes and listening to you
talk about how cool you thought you were:
So before you save the rain forest
from the parasites of your parent's generation,
try delousing the closet in your own room.

Rule 8 : Your school may have done away with winners and losers,
but life HAS NOT. In some schools, they have abolished failing grades
and they'll give you as MANY TIMES as you want to get the right answer.
*This doesn't bear the slightest resemblance to ANYTHING in real life.

Rule 9 : Life is not divided into semesters.
You don't get summers off and very few employers
are interested in helping you FIND YOURSELF.
*Do that on your own time.

Rule 10 : Television is NOT real life.
In real life people actually have to leave the coffee shop and go to jobs.

Rule 11 : Be nice to nerds.
Chances are you'll end up working for one..

Hope you enjoyed it. Take care everyone... Ian

Happiness Challenge Meditation

2012-01-04T12:53:00.003+00:00

Former Buddhist monk Andy Puddicombe guides you through a mindfulness exercise that he says will help you worry less, enjoy daily life more and get on better with the people around you

(n.b. If you can't see the video below, click here to be taken to the BBC iplayer where you can watch the video)

Andy has a fantastic website that is definitely worth a look at: http://www.getsomeheadspace.com

BattleCry (Hepatitis C / Liver Transplant & Biopsy (Hep C) HCV Blog)

2011-08-04T23:18:00.000+01:00

So here it is, the night before the day to come. The day that I have been longing for and dreading at the same time.

Tomorrow morning I report back to St Jimmy's to start my treatment for Hepatitis C, the bloody virus that has taken so much from me. I feel like I've waited so long for this day to come and yet now that it's here I'd be bloody lying if I didn't admit that I'm terrified.

Not of the fight, I'm ready for that, I'm up for it. I've been dying to pick a fight with this fucker for ages. Smack it straight in the face and shout "How do you like that you fucker? Well come back here and have some more!" and then smack it again and again and keep on smacking it and kicking it and anything else I can do to the bastard to hurt it. Until it drops down dead in front of me and even then I'll keep jumping up and down on it 'till I'm panting so bloody hard that I've got to stop. And before I walk away from it I'll kick the fucker again for good luck.

Not the pain, I'm even ready for that too. And in some ways I feel I need to feel pain to justify the enormous battle I'm fighting. I'm ready to feel my bloodied knuckles stinging and the rips and cuts of my bleeding body from the teeth and claws of this bloody thing I'm fighting.

And I'm ready for this long war of attrition. The week after relentless week of going back and fighting it again and again and again. 48 weeks of sticking myself with needles and gorging on pills and no matter how many loved ones are there for me, it will only be me who presses the needle into my skin and pushes down on the plunger. It will be a lonely battle but I'm ready for that too.

But it's the thought of defeat. That if, at the end of all the fighting and all of the pain that it might not be enough and I may need to crawl away to lick my wounds before I can return to fight another day. I'm aware I'm the underdog, that the odds are against me, but I need to finish this now, once and for all.

I don't want this life anymore. I don't even want my old life back. I want a shiny new one please, with a winners Challis to prove it.

And I'm coming to get it you fucker, I'm coming to get what's mine!

Telaprevir & Boceprevir - A potentially lethal cocktail for Post-Transplant Patients (Hepatitis C / Liver Transplant & Biopsy (Hep C) HCV Blog)

2011-07-13T08:57:00.000+01:00

Telaprevir, boceprevir, cytochrome P450 and immunosuppressive agents - A potentially lethal cocktail
(see article below editorial)

Editorial

Download the PDF here

"Finally, telaprevir has not been studied in pre-, post-, or peritransplant patients. The degree of the interaction with calcineurin inhibitors reported here suggests potential implications for patient safety. Telaprevir should not be administered to these patients, because the required studies have not been completed to understand appropriate dose adjustments needed for safe coadministration of telaprevir with cyclosporine or tacrolimus, and regulatory approval has not been obtained."

HEPATOLOGY, July 2011

Michael Charlton, MD, FRCP, Department of Gastroenterology and Hepatology, Mayo Clinic Transplant Center CH-10, Mayo Clinic, 200 First St. S.W., Rochester, MN. 55905. E-mail: charlton.michael@ mayo.edu; Fax: 507-266-1856.

Hepatitis C virus (HCV) associated liver disease continues to be the most common indication for liver transplantation. Although the impact of HCV infection varies substantially between recipients, allograft failure secondary to recurrence of HCV infection is the most frequent cause of death and graft failure in HCV-infected recipients, accounting for two thirds of long term graft loss.1 Histological features of hepatitis develop in approximately 75% of recipients in the first 6 months following liver transplantation,2 with up to 30% progressing to cirrhosis by the fifth postoperative year.2 Mortality and graft loss related to recurrence of HCV has led to long-term graft survival for recipients with HCV infection that is lower than that of recipients undergoing liver transplantation for most other indications.3 Patients who achieve sustained virological response (SVR) to treatment of posttransplant HCV infection experience less severe recurrence and lower mortality and graft loss rates than nonresponders.4-6 Although the likelihood of response to antiviral therapy varies substantially with donor and recipient IL28B genotype,7 the overall safety and efficacy of peginterferon and ribavirin in the treatment of posttransplant HCV infection are both lower than we would wish.8, 9 A recent prospective randomized controlled trial found that less than 60% of liver transplant recipients are able to complete peginterferon and ribavirin antiviral therapy and, on an intention to treat basis, the SVR rate was just over 20%.10 Results of meta-analyses and single center studies are only slightly more encouraging.11, 12 Developing safe and effective treatment of posttransplant HCV infection is one of the most important clinical challenges in our field. It has been with great anticipation that we have observed the steady progress of the lead candidate direct-acting antiviral agents, telaprevir and boceprevir, move through their respective clinical trial development, culminating in the Food and Drug Administration's (FDA) approval in May of 2011. These agents offer compelling and meaningful improvements in the efficacy of treatment of genotype 1 chronic HCV infection. In the preliminary summary of the presentations for telaprevir and boceprevir the FDA Antiviral Products Advisory Committee concluded (www.FDA.gov downloads posted May 5th 2011) that for Caucasian patients who are treatment-naïve and have genotype 1 chronic HCV infection SVR rates were 75% (telaprevir) and 69% (boceprevir). For African American patients who are treatment-naïve with genotype 1 chronic HCV infection SVR rates were 65% (telaprevir) and 53% (boceprevir). Proportional increases in efficacy of these agents over peginterferon and ribavirin are even greater among treatment experienced patients. It is expected that many patients who have taken to the sidelines awaiting the routine availability of a more efficacious anti-HCV therapy will now step forward to consider treatment or re-treatment. It is likely, and with good cause, that the expectations among patients and providers are even greater among liver transplant recipients and their physicians. In this issue of HEPATOLOGY, Garg et al.,13 report findings of a drug-drug interaction study that suggests that for transplant recipients the protease inhibitors may add peril and promise in equal measure.

Telaprevir, is an inhibitor of the enzyme cytochrome P450 3A, which is responsible for the metabolism of both cyclosporine and tacrolimus. Garg et al., conducted a Phase I, open-label, nonrandomized, single sequence study to assess the effect of telaprevir coadministration on the pharmacokinetics of a single dose of cyclosporine and tacrolimus in two separate panels of 10 healthy volunteers each. The study design is somewhat unusual and merits detailed consideration. In Part A of this study, cyclosporine was administered alone as a single 100-mg oral dose, followed by a minimum 8-day washout period, and subsequent coadministration of a single 10-mg oral dose of cyclosporine with either a single dose of telaprevir (750 mg) or with steady-state telaprevir (750 mg q8h). In Part B of the study by Garg et al., tacrolimus was administered alone as a single 2-mg oral dose, followed by a minimum 14-day washout period, and subsequent coadministration of a single 0.5-mg dose of tacrolimus with steady-state telaprevir (750 mg q8h). Coadministration with steady-state telaprevir increased cyclosporine dose-normalized (DN) exposure (DN_AUC) by approximately 4.6-fold and increased tacrolimus DN_AUC by approximately 70-fold. Similar effects were observed for elimination half-life (t1/2) of cyclosporine and tacrolimus. The authors conclude that "telaprevir increased the blood concentrations of both cyclosporine and tacrolimus significantly." The authors go on to point out that telaprevir has not been studied in organ transplant patients and its use in these patients is not recommended until the required studies have been completed and regulatory approval has been obtained. I couldn't agree more. The risk to transplant recipients of drug toxicities from inappropriate use of telaprevir cannot be overstated. Although drug-drug interaction studies with immunosuppressive agents have not been completed, as boceprevir is also known to be an inhibitor of cytochrome P450 3A4, the only safe course is to presume similar effects of boceprevir and telaprevir on calcineurin inhibitor pharmacokinetics.

It is highly responsible of Vertex to have conducted these drug-drug interaction studies and to have released the results to HEPATOLOGY so soon. The preparedness to conduct and publish these studies will, without question, save many patients from avoidable calcineurin inhibitor toxicities that would have inevitably resulted from a rush to administer telaprevir (or boceprevir) to liver transplant recipients. Sadly, the rush to treat is unlikely to be completely avoided.

We would do well to consider some of the limitations (distinct from criticisms) of the study by Garg et al., the results of which only hint at the potential for pharmacological misadventure. The first important limitation of the study is that the studies were conducted in healthy volunteers, not liver transplant recipients with recurrence of HCV. Both telaprevir and boceprevir are primarily cleared through hepatic metabolism, with only small amounts appearing in urine. As HCV infection has biologically meaningful effects on hepatic function, including inhibition of mitochondrial cytochromes,14 the effects of standard doses of telaprevir and boceprevir on CNI clearance are likely to be magnified in liver transplant recipients with HCV infection through reduced clearance and greater exposure to telaprevir and boceprevir. The effect of HCV on posttransplant cytochrome function is apparent clinically in the metabolism of tacrolimus and cyclosporine, which increases by approximately 30% following clearance of HCV in liver transplant recipients.15, 16 The effect of telaprevir/boceprevir administration on tacrolimus and cyclosporine levels and exposure is thus likely to be highly variable during the course of antiviral therapy. In addition, the effects of multiple co-administered doses of telaprevir (or boceprevir) cannot be accurately predicted from the study by Garg et al., as drug dosing only minimally overlapped in this study, probably before the maximal effect on tacrolimus and cyclosporine pharmacokinetics was achieved.

The reported magnitude of the effects of telaprevir on the pharmacokinetics of cyclosporine and tacrolimus are greater than those reported for ritonavir and lopinavir, highly potent cytochrome P450 inhibitors.17 This has important implications. A tacrolimus dose of less than 1 mg/wk can be sufficient to maintain adequate blood tacrolimus concentrations in patients on ritonavir/lopinavir, with further dosing not required for 3 to 5 weeks, depending on liver function.18

It should also be noted that cyclosporine and tacrolimus are only two of the many agents that transplant recipients receive that are metabolized by cytochrome P450. Others include sirolimus, mycophenolate, macrolides, HIV antivirals, Ca2+ channel blockers, statins, analgesics and many more. The potential for medically significant drug interactions in liver transplant recipients who might receive telaprevir/boceprevir is almost limitless.

Should any liver transplant recipients receive these HCV protease inhibitors? I would counsel that three criteria should be met by any recipient who for whom telaprevir or boceprevir is prescribed: 1. There should be evidence of aggressive histological recurrence of HCV (e.g. ≤ stage 3 fibrosis) in the absence of hepatic decompensation; 2. The patient should be treated by physicians experienced in managing complex drug-drug interactions; and 3. Treatment should be in the context of informed consent by the recipient to participate in a protocol reviewed and approved by the appropriate Insititutional Review Board/Ethics Committee.

In Samuel Beckett's play Waiting for Godot, the protagonists Vladimir and Estragon wait endlessly in vain for Godot. The tragedy is that despite both claiming Godot as an acquaintance, they hardly know him and he never arrives. Physicians treating and patients with posttransplant recurrence of HCV have similarly waited for safer and more efficacious treatments. For Vladimir and Estragon the combination of impatience and ignorance was nearly lethal. Thanks to the study by Garg et al., we know enough about telaprevir and, by inference, boceprevir to avoid turning frustration into tragedy.
----------------------------------------

Effect of telaprevir on the pharmacokinetics of cyclosporine and tacrolimus - pdf attached

HEPATOLOGY, Vol. 54, No. 1, 2011

Varun Garg,1 Rolf van Heeswijk,2 Jee Eun Lee,1 Katia Alves,1 Priya Nadkarni,1 and Xia Luo1
From the 1Vertex Pharmaceuticals Inc., Cambridge, MA; and 2Tibotec BVBA, Beerse, Belgium.

ABSTRACT

The hepatitis C virus protease inhibitor telaprevir is an inhibitor of the enzyme cytochrome P450 3A, responsible for the metabolism of both cyclosporine and tacrolimus. This Phase I, open-label, nonrandomized, single-sequence study assessed the effect of telaprevir coadministration on the pharmacokinetics of a single dose of either cyclosporine or tacrolimus in two separate panels of 10 healthy volunteers each. In Part A, cyclosporine was administered alone as a single 100-mg oral dose, followed by a minimum 8-day washout period, and subsequent coadministration of a single 10-mg oral dose of cyclosporine with either a single dose of telaprevir (750 mg) or with steady-state telaprevir (750 mg every 8 hours [q8h]). In Part B, tacrolimus was administered alone as a single 2-mg oral dose, followed by a minimum 14-day washout period, and subsequent coadministration of a single 0.5-mg dose of tacrolimus with steady-state telaprevir (750 mg q8h). Coadministration with steady-state telaprevir increased cyclosporine dose-normalized (DN) exposure (DN_AUC0-∞) by approximately 4.6-fold and increased tacrolimus DN_AUC0-∞ by approximately 70-fold. Coadministration with telaprevir increased the terminal elimination half-life (t1/2) of cyclosporine from a mean (standard deviation [SD]) of 12 (1.67) hours to 42.1 (11.3) hours and t1/2 of tacrolimus from a mean (SD) of 40.7 (5.85) hours to 196 (159) hours. Conclusion: In this study, telaprevir increased the blood concentrations of both cyclosporine and tacrolimus significantly, which could lead to serious or life-threatening adverse events. Telaprevir has not been studied in organ transplant patients; its use in these patients is not recommended because the required studies have not been completed to understand appropriate dose adjustments needed for safe coadministration of telaprevir with cyclosporine or tacrolimus, and regulatory approval has not been obtained. (HEPATOLOGY 2011;)

The global prevalence of hepatitis C virus (HCV) infection is estimated to be 130 to 170 million, with approximately 3 to 4 million persons newly infected annually.1, 2 Approximately 38,000 new HCV cases occur annually in the United States alone.3 An estimated 75%-85% of infected individuals who do not clear the virus by 6 months develop chronic hepatitis that is often associated with serious liver disease.4, 5 Cirrhosis develops in 4%-20% of patients with chronic HCV infection, leading to hepatocellular carcinoma at an annual rate of 1%-5%.6 Furthermore, cirrhosis due to chronic HCV infection is the leading cause for liver transplantation; the incidence of such cases in the United States and Europe as of 2005 was approximately 30%-50%.7

Standard treatment for chronic HCV infection includes a combination of pegylated interferon and ribavirin, shown to cause sustained viral response in 45%-50% of patients treated.8-10 In recent clinical studies, the coadministration of telaprevir, an HCV protease inhibitor, with pegylated interferon/ribavirin resulted in substantial improvements in sustained viral response compared with pegylated interferon/ribavirin alone in patients with genotype 1 chronic HCV infection (treatment-naïve patients and in patients who had failed prior standard treatment).11-15 Patients who are not eligible for standard treatment often require liver transplant due to accompanying comorbid conditions.16 Recurrence of HCV infection occurs in 100% of liver transplantations if not eradicated prior to transplantation.17 Cyclosporine and tacrolimus are immunosuppressants with narrow therapeutic ranges used in the postoperative phase of liver or kidney transplants to prevent allograft rejection. Cyclosporine and tacrolimus are substrates of both cytochrome P450 3A (CYP3A), the primary enzyme responsible for their metabolism,18, 19 and P-glycoprotein (P-gp), a transmembrane transporter.20, 21 Telaprevir is a CYP3A4 substrate and inhibitor and has the potential to saturate or inhibit P-gp in the gut (data on file, Vertex Pharmaceuticals Inc.). Therefore, coadministration with telaprevir may increase the systemic exposure to cyclosporine and tacrolimus. The current study was designed to gain an understanding of the effect of telaprevir on the single-dose pharmacokinetic (PK) parameters of tacrolimus and cyclosporine to provide guidance for dose adjustments of these drugs prior to initiation of trial(s) in transplant patients.

RESULTS

Disposition and Demographics.
The first volunteer signed the informed consent form in January 2010, and the last volunteer completed the last visit in April 2010. In Part A, all 10 volunteers received at least one dose of cyclosporine and nine volunteers received at least one dose of cyclosporine coadministered with telaprevir. Mean (SD) volunteer age was 45.8 (9.19) years, height was 167 (11.8) cm, weight was 68.5 (11.6) kg, and body mass index was 24.4 (2.56) kg/m2. The majority of volunteers were females (70%) and white (80%).

In Part B, all 10 volunteers received at least one dose of tacrolimus administered alone and nine volunteers received at least one dose of telaprevir. One volunteer was withdrawn due to noncompliance with study procedures. Mean (SD) volunteer age was 38.0 (11.0) years, height was 175 (6.73) cm, weight was 77.4 (11.7) kg, and body mass index was 25.4 (3.53) kg/m2. All volunteers were male (100%) and the majority were white (70%).

Cyclosporine Pharmacokinetics.
The dose-normalized mean (SD) blood concentration-time profiles for cyclosporine administered either alone (day 1, period 1) or with telaprevir (days 1 and 8, period 2) are presented in Fig. 1. The dose-normalized concentrations of cyclosporine were higher when coadministered with telaprevir than for cyclosporine administered alone. Without dose normalization, the cyclosporine concentrations were lower when coadministered as a 10-mg dose with telaprevir than following administration of a 100-mg dose of cyclosporine alone (concentration-time profile without dose normalization not shown). Cyclosporine concentration-time profiles were comparable on day 1, period 2 and day 8, period 2, when a 10-mg dose of cyclosporine was administered with either a single dose of telaprevir or at steady-state telaprevir.

The mean (SD) PK and statistical parameters for cyclosporine administered either alone (100-mg dose; day 1, period 1) or with telaprevir (10-mg dose; days 1 and 8, period 2) are summarized in Table 1. In Part A, a comparison of PK parameters when cyclosporine was administered alone versus coadministered with telaprevir indicated that median tmax of cyclosporine increased from 1.50 hours on day 1, period 1 to 2.50 hours on both days 1 and 8, period 2; mean Vz/F changed from 955 L on day 1, period 1 to 1,010 L on day 1, period 2 and 735 L on day 8, period 2; mean CL/F decreased from 56.3 L/h on day 1, period 1 to 14.3 L/h on day 1, period 2 and 12.5 L/h on day 8, period 2; and mean t1/2 increased from 12.0 hours on day 1, period 1 to 52.5 hours on day 1, period 2 and 42.1 hours on day 8, period 2. The DN_Cmax GLS mean ratios (90% CI) for cyclosporine coadministered with telaprevir were 1.36 (1.12, 1.65) on day 1, period 2 and 1.32 (1.08, 1.60) on day 8, period 2 compared to cyclosporine administered alone. Similarly, the DN_AUC0-∞ GLS mean ratios (90% CI) for cyclosporine coadministered with telaprevir were 4.11 (3.49, 4.85) on day 1, period 2 and 4.64 (3.90, 5.51) on day 8, period 2 compared to cyclosporine administered alone on day 1, period 1, indicating a significant effect of a single dose and steady-state telaprevir on the PK of cyclosporine.

Tacrolimus Pharmacokinetics.
The dose-normalized mean (SD) blood concentration-time profiles for tacrolimus administered either alone (2-mg dose; day 1, period 1) or with telaprevir (0.5-mg dose; day 8, period 2) are presented in Fig. 2. Tacrolimus concentrations were considerably higher when coadministered with telaprevir than for tacrolimus administered alone.

The mean (SD) PK and statistical parameters for tacrolimus administered either alone (2-mg dose; day 1, period 1) or with telaprevir (0.5-mg dose; day 8, period 2) are summarized in Table 2. In Part B, a comparison of PK parameters when tacrolimus was administered alone versus coadministered with telaprevir indicated that median tmax of tacrolimus increased from 2.25 hours on day 1, period 1 to 3.03 hours on day 8, period 2; mean Vz/F decreased from 1,910 L on day 1, period 1 to 106 L on day 8, period 2; mean CL/F decreased from 32.0 L/h on day 1, period 1 to 0.48 L/h on day 8, period 2; and mean t1/2 increased from 40.7 hours on day 1, period 1 to 196 hours on day 8, period 2. The DN_Cmax GLS mean ratio (90% CI) for tacrolimus coadministered with telaprevir was 9.35 (6.73, 13.0) on day 8, period 2 compared to tacrolimus administered alone (day 1, period 1). Similarly, the DN_AUC0-∞ GLS mean ratio (90% CI) for tacrolimus coadministered with telaprevir was 70.3 (52.9, 93.4) on day 8, period 2 compared to tacrolimus administered alone (day 1, period 1), indicating a significant effect of telaprevir on the PK of tacrolimus.

Plasma Pharmacokinetics of Telaprevir.
Mean (SD) PK parameters for telaprevir when coadministered with either cyclosporine or tacrolimus are shown in Table 3. Steady-state concentrations of telaprevir on day 8, period 2 were similar when telaprevir was coadministered with either cyclosporine or tacrolimus. Steady-state exposure of telaprevir reported in this study was comparable with historical data.22

Safety.
In Part A, adverse events of mild vessel puncture site pain (n = 1), mild pharyngitis (n = 1), mild accidental needle stick (n = 1), and moderate neutropenia (n = 1) occurred when cyclosporine was administered alone. Moderate neutropenia led to premature discontinuation of the volunteer from the study. Adverse events of mild dyspepsia (n = 1); mild rash (n = 2); mild herpes simplex (n = 1); mild contusion (n = 1); mild blood creatine phosphokinase increase (n = 1); mild somnolence (n = 1); and mild vaginal discharge (n = 1) occurred when cyclosporine was coadministered with telaprevir. Dyspepsia and rash were considered by the study investigator to be possibly related to the study drugs.

In Part B, an adverse event of mild constipation (n = 1) occurred when tacrolimus was administered alone. Adverse events of mild pruritus (n = 1) and mild excoriation (n = 1) occurred when tacrolimus was coadministered with telaprevir.

No serious, life-threatening, or severe adverse events occurred in any group. There were no notable clinically significant trends for any of the chemistry parameters, hematology parameters, vital signs, 12-lead electrocardiograms, or physical examination findings.

Discussion
The primary objective of this study was to evaluate the effect of telaprevir on the PK of single doses of cyclosporine and tacrolimus in healthy volunteers. The 100-mg cyclosporine dose and the 2-mg tacrolimus dose were chosen as they were well tolerated in healthy volunteers in previous studies.23, 24 The doses of cyclosporine and tacrolimus were lowered when coadministered with telaprevir because of the potential for marked increase in cyclosporine and tacrolimus exposure.

Dose-normalized cyclosporine exposure increased significantly when coadministered with telaprevir compared to administration of cyclosporine alone: the dose-normalized Cmax increased by approximately 1.3- to 1.4-fold, dose-normalized AUC increased by approximately 4.1- to 4.6-fold, and mean t1/2 of cyclosporine increased approximately 4-fold following coadministration of cyclosporine with either a single dose or steady-state telaprevir. Cyclosporine exposure was comparable when administered with either a single dose of telaprevir (day 1, period 2) or when telaprevir reached steady-state (day 8, period 2), suggesting an absence of time-dependent inhibition of cyclosporine metabolism by telaprevir.

The effect of telaprevir coadministration was much greater with tacrolimus: the dose-normalized Cmax increased by approximately 9.3-fold, dose-normalized AUC increased by approximately 70-fold, and the mean t1/2 of tacrolimus increased approximately 5-fold. Because of the long t1/2 of tacrolimus and the long time it would take to wash out any effect of telaprevir on its PK, the interaction with tacrolimus was only evaluated with steady-state telaprevir. It is unknown whether the magnitude of the effect of telaprevir on tacrolimus would be similar after the first dose of telaprevir, as seen with cyclosporine.

These results are significant and indicate that without understanding the adjustments required for dose and/or dosing frequency of cyclosporine and tacrolimus, telaprevir coadministration could lead to serious or life-threatening adverse events. The mechanism for the greater effect of telaprevir on the PK of tacrolimus compared to cyclosporine is unknown, but may be related to lower bioavailability of tacrolimus (≈18%) in healthy volunteers,19 making it more susceptible to CYP3A and/or P-gp inhibition in the gut and during first-pass metabolism. This is also suggested by the 9.3-fold increase in the tacrolimus Cmax and the sharp decrease in the mean (SD) apparent volume of distribution (Vz/F) of tacrolimus from 1,910 (859) L when administered alone to 106 (34) L (Table 2) in the presence of telaprevir (i.e., an increase in oral bioavailability, F, without a proportional change in volume of distribution, Vz, may decrease the ratio, Vz/F closer to the reported value of Vz, corrected for F, in healthy volunteers of 1.94 L/kg19). In contrast, there was no apparent change in the Vz/F of cyclosporine after the first or last telaprevir dose (Table 1) compared to cyclosporine administered alone, suggesting that bioavailability of cyclosporine was not changed in the presence of telaprevir, consistent with the observed modest effect of telaprevir on the Cmax of cyclosporine. However, the bioavailability of cyclosporine varies considerably depending on patient population (ranging from <10% in liver transplant patients to 89% in some kidney transplant patients).18 Therefore, the effect of telaprevir on cyclosporine concentrations in liver transplant patients may differ from that observed in this healthy volunteer study, and close monitoring of cyclosporine concentrations to guide individual dose adaptations would be necessary during coadministration.

The decrease in hepatic clearance and increase in t1/2 of both cyclosporine and tacrolimus upon telaprevir coadministration suggests that systemic clearance of these immunosuppressants was also reduced by telaprevir. The effect of telaprevir on hepatic transporters that could have contributed to lower clearance or enhanced absorption is unknown.

Notably, in this study the effect of steady-state telaprevir on the PK of cyclosporine or tacrolimus was evaluated only at single doses of these immunosuppressants. Because the elimination half-lives increased significantly for both cyclosporine and tacrolimus when telaprevir was coadministered, without proper adjustment of dose and dosing interval of these immunosuppressants, further increases in blood exposure may occur when multiple doses of these drugs are coadministered with telaprevir. However, studies of telaprevir with multiple doses of cyclosporine and tacrolimus have not been performed.

The effects of telaprevir on cyclosporine and tacrolimus exposure were similar to that reported for human immunodeficiency virus (HIV) protease inhibitors known to be potent CYP3A inhibitors, where significant reductions in dose and/or dosing interval of immunosuppressants were needed to achieve the desired range of trough concentrations, based on frequent monitoring of trough concentrations of the immunosuppressants.25 For example, addition of lopinavir/ritonavir (n = 7 patients) reduced tacrolimus dose by 99% to maintain tacrolimus concentrations within the therapeutic range.26 Similarly, during coadministration of Highly Active Antiretroviral Therapy (HAART) regimens with ritonavir-boosted HIV protease inhibitors, daily cyclosporine doses were reduced by 80%-95% to maintain cyclosporine exposure at pre-HAART levels. Because of the flat absorption/elimination profiles of cyclosporine during combination with ritonavir-boosted HAART therapy, cyclosporine exposure could be reliably monitored long-term by measuring cyclosporine trough concentrations.27 Treatment of posttransplant patients coinfected with HIV/HCV with antiretrovirals and telaprevir could be even more challenging, depending on the drugs involved. Telaprevir levels are not significantly affected by ritonavir28; however, whether the net effect of antiretroviral drugs on cyclosporine and tacrolimus PK would be similar or different is hard to predict, as these drugs may have their own effects. The PK of tacrolimus and cyclosporine may also vary based on CYP3A5 genotype.29 Therefore, the effect of telaprevir on these drugs may also vary based on CYP3A5 genotype.

Although cyclosporine is a CYP3A and P-gp inhibitor,18 the effects of a single cyclosporine dose on systemic telaprevir exposure were considered negligible, because the cyclosporine dose (10 mg) was low and administered 2 hours after telaprevir administration. This study was not designed to test the effect of cyclosporine and tacrolimus on telaprevir exposure. However, telaprevir steady-state exposure in Parts A and B were similar to previous Phase I studies,22 so it is unlikely that coadministration of cyclosporine or tacrolimus had a relevant effect on telaprevir exposure.

Food decreases cyclosporine and tacrolimus exposure (Cmax by 33% and 65%; AUC by 13% and 28%, respectively),18, 19 whereas telaprevir exposure increases with food. Telaprevir was administered 30 minutes after the start of a meal and cyclosporine or tacrolimus were administered 2 hours after telaprevir during coadministration. Volunteers refrained from further food or drink during the period between administration of telaprevir and cyclosporine or tacrolimus. This approach was used to minimize food effect on cyclosporine and tacrolimus exposure, while providing appropriate telaprevir dosing conditions. The extent to which simultaneous telaprevir administration with cyclosporine or tacrolimus in the fed state would impact these results is unknown.

Another important consideration about concomitant tacrolimus or cyclosporine use with telaprevir in organ transplant patients is that after telaprevir treatment is completed or stopped, its inhibitory effect on CYP3A/P-gp would wear off and doses of immunosuppressant would need readjustments. Estimates of the recovery time of CYP3A activity vary widely30 and precise timing for CYP3A activity to resume to the levels before the start of telaprevir is unknown. Therefore, careful blood concentration monitoring of immunosuppressants will be needed for approximately 2 weeks after telaprevir is stopped.

Besides cyclosporine and tacrolimus, other immunosuppressants that are likely to have a significant interaction with telaprevir include those known to have increased exposures when coadministered with strong CYP3A inhibitors, such as sirolimus and everolimus. Exposure of corticosteroids known to be metabolized by way of CYP3A may also increase in the presence of strong CYP3A inhibitors. However, studies with these drugs in combination with telaprevir have not been conducted.

Finally, telaprevir has not been studied in pre-, post-, or peritransplant patients. The degree of the interaction with calcineurin inhibitors reported here suggests potential implications for patient safety. Telaprevir should not be administered to these patients, because the required studies have not been completed to understand appropriate dose adjustments needed for safe coadministration of telaprevir with cyclosporine or tacrolimus, and regulatory approval has not been obtained.

An Open Letter To Those Without HCV (Hepatitis C / Liver Transplant & Biopsy (Hep C) HCV Blog)

2011-07-03T20:24:00.000+01:00

Hi Folks,

I wish I could take credit for this 'open letter' which describes almost exactly how most of us feel who are trying to cope with the effects of this virus, but I can't.
I found it on the very excellent 'Hep C Nomads' website which is a forum for those who have HCV and their carers.
For me, the Hep C Nomads site has not been just an excellent source of information but more than that, I have met many courageous and inspiring individuals who helped me through some of the hardest of times of my continuing fight with this disease. I continue to be in their debt.

For anyone who has Hepatitis C or is affected by this virus, I would strongly recommend that they register with this forum. Links to their site can be found by clicking on the links on this page or by clicking on their site and facebook links & logo's to either side of this page.

Take care everyone... Ian

An Open Letter To Those Without HCV (Hepatitis C Virus)

Having Hepatitis C means that many things change. Just because you can't see the changes doesn't mean they aren't real.

Most people don't understand much about this disease or the disability the treatment causes and their effects, and of those that think they know many are actually misinformed. In the spirit of informing those who wish to understand.....

These are the things that I would like you to understand about me before you judge me.

Please understand that HCV and its treatment doesn't mean I'm not still a human being. I have to spend most of my day being very careful what I do, and if you visit I might not seem like much fun to be with, but I'm still me stuck inside this body. I still worry about school and work and my family and friends, and most of the time I'd still like to hear you talk about yours too.

Please understand the difference between "happy" and "healthy". When you've got the flu you probably feel miserable with it, but I've been sick for years. I can't be miserable all the time, in fact I work hard at not being miserable. So if you're talking to me and I sound happy, it means I'm happy. That's all. I may be tired. I may be in pain. I may be sicker than ever. Please, don't say, "Oh, you're sounding better!" I am not sounding better, I am sounding happy. If you want to comment on that, you're welcome.

Please understand that being able to stand up for five minutes, doesn't necessarily mean that I can stand up for ten minutes, or an hour. It's quite likely that doing those five minutes has exhausted my resources and I'll need to recover - imagine an athlete after a race. They couldn't repeat that feat right away either.

Please repeat the above paragraph substituting, "sitting up", "walking", "thinking", "being sociable" and so on ... it applies to everything that I do.

Please understand that HCV and its treatment are variable. It's quite possible (for me, it's common) that one day I am able to walk to the park and back, while the next day I'll have trouble getting to the kitchen. Please don't scold me when I'm ill by saying, "But you did it before!" If you want me to do something, ask if I can and I'll tell you. In a similar vein, I may need to cancel an invitation at the last minute, if this happens please don't take it personally.

Please understand that "getting out and doing things" does not make me feel better, and can often make me worse. HCV (and if on treatment) may cause a secondary/reactive depression but they are not caused by depression. Telling me that I need some fresh air and exercise is not correct and probably not appreciated - if I could possibly do it that, I would.

Please understand that if I say I have to leave/sit down/lie down/take these pills now, that I do have to do it right now - it can't be put off or forgotten just because I'm doing something else more exciting. HCV does not forgive their victims easily.

Please understand that I can't spend all of my energy trying to get well from my chronic illness. With a short-term illness like the flu, you can afford to put life on hold for a week or two while you get well. But an important part of having a chronic illness is coming to the realization that you have to spend energy on having a life while you're sick/disabled. This doesn't mean I'm not trying to get better. It doesn't mean I've given up. It's just how life is when you're dealing with a chronic illness and its treatment.

If you want to suggest a cure to me, please don't. It's not because I don't appreciate the thought; and it's not because I don't want to get well. It's because I have had many people suggest one at one point or another. At first I tried to research or try them, but then I realized that I was using up so much energy looking for answers that I was making myself sicker, not better. If there was something that cured, or even helped, all people with a certain illness or disability then we'd know about it. This is not a drug-company conspiracy, there is worldwide networking (both on and off the Internet) between people with similar and different chronic illnesses and disabilities, and if something worked we would know about it.

If after reading that, you still want to suggest a cure, then do it if you must. Preferably in writing and accompanied by the scientific papers that prove it works. But don't expect me to rush out and try it. I might not even reply. If I haven't had it or something like it suggested before, and it sounds reasonable, I'll probably take what you said and discuss it with my doctor.

Please understand that getting better from an illness can be very slow. And getting better might not happen at all. People with Chronic HCV have so many systems in their bodies out of equilibrium, and functioning wrongly, that it may take a long time to sort everything out, if it ever happens. But most importantly, I need you to understand me.

by Beth Oberin via Hep C Nomads

Hepatitis C and its Effects on Liver Transplantation (video) (Hepatitis C / Liver Transplant & Biopsy (Hep C) HCV Blog)

2011-06-29T13:02:00.000+01:00

Hi Folks,
As many of you will know, a subject very close to my heart and exactly what I am facing right now.
take care everyone... Ian

Hepatitis C and its Effects on Liver Transplantation
via HCV New Drug Research

Dr. K. Rajender Reddy, the Medical Director of liver transplantation at the Penn Transplant Institute, discusses the viral epidemic of hepatitis-c and its effects on liver transplantation.

Learn more about liver transplantation at the Penn Transplant Institute: http://www.pennmedicine.org/transplant/patient/liver/

View Dr. K. Rajender Reddy's profile: http://www.pennmedicine.org/wagform/mainpage.aspx?config=provider&p=pp&am...

See this video on YouTube:

http://www.youtube.com/watch?v=wtuwErTz_j0&feature=player_embedded

Dr. Reddy was interviewed by Andrew Schorr, host and founder of Patient Power, at the 2011 American Transplant Congress.

I'm Ready To Fight Back! (Hepatitis C / Liver Transplant & Biopsy (Hep C) HCV Blog)

2011-06-25T01:30:00.000+01:00

A letter to my MP for the Hep C Trust (Hepatitis C / Liver Transplant & Biopsy (Hep C) HCV Blog)

2011-06-15T11:21:00.000+01:00

Hi Folks,

I have just taken part in an action to help raise awareness and understanding about hepatitis C in Parliament.

Please take action and contact your MP too!

Please click on the link below to write to your MP now:

http://e-activist.com/ea-campaign/clientcampaign.do?ea.client.id=1667&ea.campaign.id=7408

My MP is Mr Edward Leigh, MP for Gainsborough and this campaign is being coordinated by the Hep C Trust.

My Letter reads as follows:

Dear Mr Leigh,

I am writing to raise the issue of hepatitis C, a virus that has had a huge impact on my life.

As you may be aware, hepatitis C is a growing problem in the UK. It is an infectious blood-borne virus that mainly affects the liver and is undiagnosed in the majority of the 250,000 to 466,000 people infected across the UK. It can cause cirrhosis of the liver, liver cancer and death yet is both preventable and treatable.

I am Hepatitis C sufferer and it is thought I contracted the virus over 25 years ago.

Unfortunately for me, by the time I was diagnosed with HCV, my liver was so badly damaged that my only option was to have a full Liver Transplant.

I received my new liver on 28th January 2010 at St James Hospital, Leeds which gave me a new lease of life but I still have the Hepatitis C virus.

I am aware that new drugs will soon be available to combat this deadly virus however these are not yet available on the NHS and nor have they been tested on post-liver transplant patients.

I am about to embark on the currently available, standard Ribavirin/Peg Interferon treatment which will take 48 weeks to complete which does not guarantee a 'cure' and has severe side effects. I am also told I will not qualify for DLA whilst on this treatment which I find cruel and unjust.

All of this suffering could have been avoided, as well as the expense of the Liver Transplant operation, the extremely expensive drugs I must now take for the rest of my life and the treatment I am about to start IF I HAD BEEN DIAGNOSED EARLY.

The Department of Health is currently developing a National Liver Strategy and I hope this will address hepatitis C and its devastating consequences by drastically increasing diagnosis rates, improving support, treatment and care for patients, and preventing further infections.

The All-Party Parliamentary Hepatology Group takes a lead in Parliament in raising the profile of liver disease, in particular hepatitis C. I would be extremely pleased if you could join the Group so you can be kept up to date with relevant debates, reports and meetings in Westminster. The Hepatitis C Trust runs the secretariat for the Group so please email jane.allen@hepctrust.org.uk or call 020 7089 6220 to join. This is very important to me and I do hope you will be able to support me and other hepatitis C patients in this way.

I would also be grateful if you could consider supporting Early Day Motion 119, ‘The Hepatitis C Trust’s Get Tested Campaign’ which calls for great public and professional awareness of the virus so that more people are diagnosed.

I urge you as my MP to join the All-Party Parliamentary Hepatology Group and support our Early Day Motion, ‘The Hepatitis C Trust’s Get Tested Campaign’.

I would appreciate if you could write back to me to let me know your thoughts on my request.

Thank you for your time and your consideration of this vital but often overlooked public health issue.

Yours sincerely,

Ian Quill

Please could I ask anyone reading this in the UK to join this campaign and write to their MP by clicking on this link: http://e-activist.com/ea-campaign/clientcampaign.do?ea.client.id=1667&ea.campaign.id=7408

Take care everyone... Ian

Treating Hepatitis C With Telaprevir (video) (Hepatitis C / Liver Transplant & Biopsy (Hep C) HCV Blog)

2011-06-11T14:51:00.000+01:00

Treating Hepatitis C With Telaprevir.mp4

From: HCVNEWDRUGS
This Video Covers Treating HCV with the new drug telaprevir in combination with Pegylated interferon and Ribavirin.

Click Below For More Information: Hepatitis C New Drugs and Liver Health
http://hepatitiscnewdrugresearch.com/telaprevirboceprevir...

Blog: HCV New Drug http://hepatitiscnewdrugs.blogspot.com/

VICTRELIS Boceprevir - How Long Will I Be On Treatment (video) (Hepatitis C / Liver Transplant & Biopsy (Hep C) HCV Blog)

2011-06-10T16:27:00.000+01:00

WITH THANKS &Uploaded by HCVNEWDRUGS (a truly excellent source of information for everthing related to HepC)

Treating Hepatitis C With The New FDA Approved Oral Drug VICTRELIS plus standard treatment.

VICTRELIS™- Boceprevir: Prescribing Information and Medication Guide

Coffee drinking improves Hepatitis C treatment response (Hepatitis C / Liver Transplant & Biopsy (Hep C) HCV Blog)

2011-06-07T20:29:00.000+01:00

Mmm.. Coffee, I knew I loved drinking it so much for a reason. And after drinking several strong 'blasts' in the morning, I find I get so much more achieved. And now they tell me 'it's good for you'...Should help with my forthcoming treatment, I have a treatment review on Monday at St Jimmy's. So for now, I'll have another shot then please :)

Advanced hepatitis C patients with chronic liver disease may benefit from drinking coffee during treatment, according to a new study in Gastroenterology, the official journal of the American Gastroenterological Association (AGA) Institute. Patients who received peginterferon plus ribavirin treatment and who drank three or more cups of coffee per day were two times more likely to respond to treatment than non-drinkers.

"Coffee intake has been associated with a lower level of liver enzymes, reduced progression of chronic liver disease and reduced incidence of liver cancer," said Neal Freedman, PhD, MPH, of the National Cancer Institute and lead author of this study. "Although we observed an independent association between coffee intake and virologic response to treatment, this association needs replication in other studies."

Among non-drinkers, 46 percent had an early virologic response; 26 percent had no detectable serum hepatitis C virus (HCV) ribonucleic acid at week 20; 22 percent had no detectable serum at week 48; and 11 percent had a sustained virologic response. In contrast, the corresponding proportions for those who drank three or more cups of coffee per day were 73 percent, 52 percent, 49 percent and 26 percent, respectively.

Approximately 70 to 80 percent of individuals exposed to HCV become chronically infected. Worldwide, these individuals are estimated to number between 130 and 170 million. Higher coffee consumption has been associated with slower progression of pre-existing liver disease and lower risk of liver cancer. However, the relationship with response to anti-HCV treatment had not been previously evaluated. Treatment with peginterferon and ribavirin resolves chronic hepatitis C in about half of patients. It is unknown whether coffee will improve response with the addition of new drugs that were recently approved for use in the U.S.

Because patients in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial also had previously failed interferon therapy, it is not clear whether the results can be generalized to other patient populations. Future studies among patients with less advanced disease, those who are treatment-naïve to prior therapy, or who are being treated with newer antiviral agents are needed.

With thanks to: Science Codex

Source: American Gastroenterological Association

Hepatitus C Made Simple (video) (Hepatitis C / Liver Transplant & Biopsy (Hep C) HCV Blog)

2011-04-25T21:19:00.000+01:00

Hi to everyone, just a video about Hep C explaining what the virus is and how it operates. In this vid it says "HepatitisC can be cured" - I suppose they sound very optimistic as it was created by Vertex Pharmaceuticals, the company who are just about to launch 'Teleprevir', the latest drug for the war on HCV.
There is no doubt that this drug, and 'Boceprevir' that is also about to be launched, represent a huge leap forward in the fight against this terrible virus that affects 4 times as many people in the world than Aids and for so many people who are infected, they have no idea that they have it until it becomes a life threatening illness. What it doesn't say is that even with these new drugs, there is still no definitive cure...
take care everyone... Ian

Another Letter to Ali (Hepatitis C / Liver Transplant & Biopsy (Hep C) HCV Blog)

2011-04-22T01:36:00.000+01:00

I thought I would share this letter that I sent to Ali and readers of this blog will know this is not the first time I have posted our letters here.
Ali's a good friend of mine whom I've known since way back when, through good times and bad. I sometimes wish I was as good a friend to her as she has always been for me and even though we are now many miles and countries apart, she continues to support me in so many ways.

Dear Ali, How are you and how is beautiful Chamonix?
Well, I finally managed to track down my HepC nurse at our local hospital and after badgering her a bit (It has been nearly a month and a half since St Jimmy's handed me over to them to start my treatment) I finally got a date from her for the start of my treatment... I think.
Friday 6th May is when I'll be going to see them to start treatment. Apparently she's been having to study the protocol for dealing with transplant patients as she's never dealt with one before.... Yikes!!
I'm sure it will be OK and she will be in regular touch with my doctors at Jimmy's and I'll be very closely monitored. You know my old saying "It'll be all-right!!!"

Thank-you to you and Mo for doing the healing meditations, I can't believe how well they've worked. I know you think Benny would frown on spiritual meditation as "a load of bollocks and all that" (and at one time I would've been right there with him) but if he ever needed proof that it works then he needn't look any further.

It really has lifted me in my mind and I feel physically better than I have done for a long time and don't just take my word for it, even Mandy's amazed. And Mandy is not a spiritual believer in the way we are but she can't believe the change in me.

I've also had Jenny saying Buddhist 'chants' or prayers for me as apparently shes quite into that, It was great to see her again and she hasn't changed a bit, the rotten cow!
Anyway, it was quite interesting hearing her talking about her religion but I don't think I could ever embrace it in it's entirety but as with the spiritual meditations, I think there must be something to it.
I've been looking into meditation quite a bit anyway after our success with it. I certainly haven't 'found God' or 'seen the light' yet but Jenn probably put it right when she said "I think they're all paths to the same thing" and essentially I think shes probably right.

I'm not sure if, since we started the meditation, everything is going exactly to plan (far from it sometimes) but I certainly feel like I'm coping with it a lot better.
I'm better at dealing with the fear of the unknown so much better now and that's got to be a good thing. I've certainly had plenty of that in the last couple of years.
But although the fear never quite goes away entirely, it just feels like I've got a kind of scary, hairy creature thumping around inside me all the time at the back of my mind.
It's all the things that have haunted me and now I no longer see 'it' staring me in the face. But sometimes I can hear it moving around and I can hear it's breathing and grunting somewhere way back in the darkness of my mind where I have put it and I just have to tell myself that it cant hurt me anymore because it's locked up in it's cage back there.
And then I try and think back to the meditations and I can feel it getting further and further away, like I'm walking out from a dark passage where it lives and out into the light where you and Mo are and all the other people who are fighting this thing with me. I can hear their voices and see their smiles and feel the warmth and the safety and then I'm back, and that's it - life can go on again without all that weight on me.

I'm so glad we spoke on the phone when we did, I was pretty low at that point, as anyone who's had or has this virus knows, you get good days and some very bad. It's difficult to explain to people, now that I've recovered from the transplant op and you look okay on the outside and some days you feel okay too, and then others when you can't get out of bed because you feel so fatigued or you just can't face the world and are in a place that I though I would never go. I suppose people will have to live and learn as I have had to.

OK chicken, I'll get off, write me back soon and I guess we'll both keep looking out for each other.

Take care.... Rio xx

Adverse Effects: Management of Hepatitis C Antiviral Therapy (Hepatitis C / Liver Transplant & Biopsy (Hep C) HCV Blog)

2011-04-17T09:07:00.000+01:00

Hi folks, I thought it was time I researched and put something on my blog about my forthcoming treatment. And, as everyone I talk to who doesn't have HepC keeps asking me about the treatment and about the side effects I thought I'd post some information for all of us to read.
The treatment I will be having is standard Ribavirin & Pegylated Interferon therapy and will hopefully rid me of the Hepatitis C Virus (HCV) - this is the reason why I had a Liver Transplant just over 14 months ago.
I understand that if I clear this virus it will be considered extraordinary and to date, I have not come across any geno 1a (my geno-type) who has been cured or achieved 'Sustained Virological Response' (SVR) as it is known medically.
I found this info on the very excellent 'HCV New Drug Research' blog, sorry if it's heavy reading but I'm aware that they're very heavy drugs to treat a very heavy virus and I will be entering into this treatment with some trepidation but overall positive attitude.
take care everyone... Ian

Management of Hepatitis C Antiviral Therapy Adverse Effects

Hepatitis C is one of the leading causes of liver disease in the United States, affecting more than 4 million individuals. The current treatment regimen involves pegylated interferon in combination with ribavirin. Although antiviral treatment has been associated with a greater than 50% sustained viral response rate, the adverse effects have proven to be detrimental to quality of life and therapy adherence, and consequently lead to lower sustained viral response rates. This article identifies the most frequently described complications associated with pegylated interferon and ribavirin. The active management of these complications is discussed, including both preventive and empiric treatments.

Keywords: Hepatitis C virus, Pegylated interferon, Ribavirin, Side effects, Management

Introduction

Hepatitis C is a major public health concern. With almost 4 million Americans with chronic infection, hepatitis C is the one of the leading causes of chronic liver disease and is the single most common indication for liver transplantation [1–3]. Antiviral therapy is effective in more than half of infected patients, but the actual rate of sustained viral response depends on viral, host, and adherence factors. Viral and host factors tend to be nonmodifiable, whereas interventions may increase adherence.

The current standard of care for hepatitis C therapy is the combination of pegylated interferon and ribavirin [4]. Sustained viral response for antiviral therapy is about 55% [5•, 6•]. However, adverse effects from antiviral therapy directly affect treatment adherence and can decrease the likelihood of a sustained viral response. These complications can severely compromise quality of life [7]. Both interferon and ribavirin are associated with signature effects that are predictable, manageable, and improve with dose modification or discontinuation [8••]. Rarely is an adverse effect from hepatitis C antiviral therapy permanent. Adverse effects can arise from both interferon and ribavirin, and may lead to treatment termination and dose modifications in 10% to 15% and 32% to 42% of patients, respectively [5•, 6•, 9]. When interferon and ribavirin doses are reduced by a certain threshold, the sustained viral response may also decrease [10]. For instance, the results of a recent study by Reddy et al. [11••] demonstrated the sustained viral response is 34% when a patient’s cumulative ribavirin dose decreases below 60%.

An understanding of the antiviral adverse effects is essential to effectively deal with adverse effects in a timely manner. The goal during therapy is to maximize the likelihood of achieving a sustained viral response while improving tolerability and maintaining quality of life. Providers should discuss the potential issues with patients and with their social support. During clinic follow-up, patients should be queried about treatment adverse effects. Many times, the adverse effects can accumulate over time and lead to early treatment discontinuation. The current paper reviews the most frequent adverse effects associated with hepatitis C therapy, and proposes interventions to ameliorate complications. The adverse effects from pegylated interferon and ribavirin are considered separately.

Pegylated Interferon

The efficacy and therapeutic value of hepatitis C treatment is dependent on the degree of tolerability and adherence to the drugs, which in turn are related to the management of the side effects. The frequency and number of side effects related to interferon therapy are common, with most clinical trials reporting at least one interferon-related adverse effect in 95% of the patient group [5•, 10, 12]. The most frequently reported adverse effects from interferon include constitutional, hematologic, neuropsychiatric, and endocrinologic complications See; (Table 1). The onset of the adverse effects differ. The onset can be from minutes after the interferon injection, to months See; (Table 2).

Constitutional Effects

The most common adverse effects from interferon are constitutional symptoms. The severity of these side effects is inversely related to the amount of time after the interferon injection. Fatigue, headache, and fever were each reported in about 50% to 60% of treated patients [6•, 9, 12].

Constitutional effects can manifest early during therapy, even after the first dose of interferon [12]. However, several constitutional effects (e.g., fever) resolve or wane after the first several injections. Certain precautions can assist with the effects, such as maintaining adequate hydration and light to moderate exercise. The suggested intake of water in ounces is equivalent to half the patient’s body weight in pounds. To prevent interferon therapy from interfering with work, injections should occur on Fridays. As a result, most of the constitutional effects will occur on Saturday. By Monday, treated patients tend to feel better. The use of acetaminophen or ibuprofen before the injection can also ameliorate many of the constitutional adverse effects. Other adverse effects (e.g., arthralgia) can respond to acetaminophen or ibuprofen. However, ibuprofen should be avoided in patients with liver cirrhosis.

Hematologic Effects

Hematologic side effects are the most recurrent abnormal laboratory values that can lead to dosage reductions and premature treatment termination [9]. Because of its myelosuppressive effect, interferon can affect hemoglobin, white blood cell, and platelet values. However, the anemia seen during combination treatment is mostly associated with ribavirin-induced hemolytic anemia.

The definition of neutropenia varies between the two commercially available pegylated interferons. For instance, neutropenia is defined as an absolute neutrophil count less than 500 cells/mm3 when using pegylated interferon α-2a, and below 750 cells/mm3 when using pegylated interferon α-2b [13, 14]. Certain populations appear to be more likely affected by the neutropenic effects of interferon, such as the elderly and non-African Americans [15]. Although African Americans are prone to constitutional neutropenia, initiation of interferon treatment usually only leads to minimal further decreases in neutrophil count. However, the clinical impact of neutropenia on significant infection is controversial. In a study of 119 subjects, 22 infections were documented and were dominated by sinusitis, pharyngitis, and urinary tract infections [15].

In most clinical trials, neutropenia is treated with dose modification. Interferon dose reduction occurs in about 17% to 20% of patients and treatment termination in 2% to 3% of patients [16••, 17, 18]. The rapid decline in neutrophils usually occurs within the first 2 weeks of treatment initiation, with stabilization occurring over the next 4–6 weeks [9]. One study of 25 patients illustrated a median drop of 21% in neutrophils following the first dose of interferon [19].

Another option for patients who develop neutropenia from interferon therapy is the use of granulocyte colony-stimulating factor (GCSF) [20–22]. Few clinical studies have included the use of GCSF [20, 21]. These studies have indicated that the GCSF is able to raise neutrophil counts during interferon therapy. However, the results of a recent study failed to show a correlation between interferon-induced neutropenia and incidence or severity of infections [15]. Thus, although GCSF can improve neutrophil counts, future studies are required to determine the utility of GCSF in clinical practice, particularly given its increased costs and its own associated adverse effects. Regardless of the intervention of neutropenia, affected patients need regular cell counts to monitor neutrophil levels.

Another interferon-induced hematologic adverse effect is thrombocytopenia. Several mechanisms exist for the development of thrombocytopenia. It has been shown that platelet count can fall up to 50% because of posttranscriptional suppression of megakaryopoiesis or platelet sequestration in capillaries [23]. In addition, there have been rare cases of immune-mediated thrombocytopenia leading to significant decreases in platelet count, which can be rectified by termination of interferon treatment or corticosteroid therapy [24, 25]. Platelet reduction often occurs within the first 24 h of interferon administration, with nadir being reached within 8 weeks of therapy. Platelet levels will then stabilize at this low level during the length of therapy [23, 24]. However, it may compound the already present thrombocytopenia associated with cirrhosis and portal hypertension. With pegylated interferon α-2a, dose reduction is suggested when platelet counts fall below 50,000/mL and therapy termination when counts fall below 25,000/mL [13]. The threshold is set a little higher with respect to pegylated interferon α-2b, with limits of 80,000/mL for dose reduction and 50,000/mL for discontinuation [14]. Discontinuation of therapy is often followed by normalization of platelet counts within 4–8 weeks [23, 24]. Recent studies have shown eltrombopag, a thrombopoietin receptor agonist, to effectively increase platelet counts to greater than 250,000/mm3 in thrombocytopenic patients with hepatitis C virus [26]. However, its safety and utility in patients with advanced liver disease remains to be determined, because it may increase the risk of thrombosis [27].

Neuropsychiatric Effects

Not only is the prevalence of depression in patients with hepatitis C higher than the general population, antiviral therapy increases the likelihood of a variety of neuropsychiatric complications, including worsening depression, anxiety, and suicidal ideation [28]. Thus, it is imperative to assess for underlying depression and other preexisting psychiatric illness before considering antiviral therapy. In fact, antiviral therapy is contraindicated in patients with uncontrolled neuropsychiatric disorders. With a treated patient’s approval, it is helpful for their social support to provide feedback on mood changes because patients themselves may not notice changes in their disposition.

About 20% to 30% of patients treated with interferons report depression during therapy or the exacerbation of a preexisting depressive state [6•, 29]. Depending on the type and severity of neuropsychiatric effects, patients may be monitored or may be treated with more frequent clinic visits or telephone calls, antidepressant medications, psychiatric referral, or dose modification or even discontinuation.

The selection of antidepressant medication requires tailoring, because depression may have nuances that improve or worsen with the choice of therapy [30]. The greatest experience with antidepressant medications is with selective serotonin reuptake inhibitors (SSRIs) [31, 32]. Although the use of antidepressant medication may not necessarily significantly improve the likelihood of a sustained viral response, it does improve adherence and help maintain quality of life [33]. In patients believed at increased risk of interferon-associated depression, preemptive treatment with SSRIs was associated with a significant reduction in the incidence of major depression [33].

Endocrinologic Effects

Thyroid abnormalities are the most commonly associated interferon-induced endocrinologic adverse effect, occurring in 1% to 6% of interferon-treated patients [34, 35]. Both hypo- and hyperthyroidism can develop. Patients with hepatitis C may be predisposed to developing thyroid abnormalities because of an increased rate of thyroid autoantibodies prior to starting antiviral therapy [36]. For instance, one study described the development of thyroid disorder in 60% of patients with antithyroid microsome antibodies present prior to the initiation of interferon therapy, compared to only 3.3% of patients without these antibodies [35]. In a similar study, 38.5% of females with antithyroid peroxidase antibodies developed hypothyroidism versus only 7.8% of females lacking these antibodies [37].

Thyroid function tests should be obtained at baseline and every 12 weeks during antiviral treatment, and after treatment completion. If a patient develops symptomatic hypothyroidism, hormone replacement should be initiated while continuing antiviral therapy. Moreover, if the patient develops hyperthyroidism, the patient should be referred to an endocrinologist for further management with reevaluation of the antiviral regimen. Similar to the autoantibody destruction seen in the thyroid, antibodies to the adrenal cortex, pancreatic islet cells, and antiphospholipid antibodies have been reported with the use of interferon [38, 39]. Although rare, new-onset insulin-dependent diabetes mellitus with the presence of antibodies directed toward islet cells and insulin has been reported [40].

Dermatologic Effects

Many dermatologic adverse effects are associated with interferons, with an incidence ranging from 13% to 87% [5•, 41]. Besides nonspecific symptoms, reactions at the site of interferon injection are common, with 30% to 40% of patients complaining of erythema, pruritus, and tenderness [6•, 42]. Because the lesions may take weeks to resolve, it is recommended to rotate between unique injection sites. After injection, the sites are often warm and raised, expanding to a circumference of 5 cm or more. If the site continues to enlarge and remains warm and tender, the patient must be examined for possible abscess formation. Rarely, infection and skin necrosis are seen at the injection site. However, these symptoms do not necessarily warrant termination of treatment.

An additional major complaint from interferon therapy is skin dryness, which occurs in two of three treated patients [43]. Skin dryness can be exacerbated in cold weather, and may be accompanied by intense pruritus. Topical steroids, emollients, and soothing baths may help to alleviate these symptoms, but studies have not shown a significant response [43]. Another typical adverse effect seen with interferons is alopecia, occurring in about one third of patients, with a higher prevalence in females [44]. To combat alopecia, the patient can cut his/her hair short prior to interferon initiation and avoid pulling, braiding, or vigorously combing the hair. In addition, patients should avoid the use of harsh hair-care products, harsh hair dyes, hair dryers, and other products that may be detrimental to hair growth.

Other Effects

Neurologic, pulmonary, and ophthalmologic adverse effects associated with interferon use have been reported. Sensory and autonomic neuropathies, as well as Bell’s palsy, have been documented with interferon use, most likely arising from an autoimmune phenomenon or neuronal injury caused by interferon stimulation of the immune system [45]. Neuropathy usually resolves with the termination of interferon treatment, but additional steroids and/or cyclophosphamide may be beneficial [12]. In addition to the neuropathies stated, there have been rare cases of myasthenia gravis. In such cases, interferon therapy is withdrawn and pyridostigmine therapy is initiated [46]. During interferon treatment, multiple pulmonary adverse effects can occur, such as interstitial pneumonitis, alveolar disease, and sarcoidosis reactivation. If a patient complains of continual cough and dyspnea on exertion or rest, a chest radiograph should be obtained to exclude pneumonitis. Possible bacterial pneumonia should be treated with proper antibiotics in conjunction with halting antiviral therapy, which can be reinitiated when there is clinical improvement. Occasionally, pulmonary function tests may be indicated, including forced vital capacity, forced expiratory volume, and carbon monoxide diffusion capacity, as well as a thoracic CT scan. Interferon-induced interstitial pneumonitis can be life-threatening, although it usually resolves with withdrawal of interferon. However, the most common cause for cough and shortness of breath is likely ribavirin-induced [43].

In addition to the pulmonary and neurologic effects, interferons have been associated with retinopathy (e.g., retinal hemorrhages and cotton wool spots), particularly in patients with diabetes [47]. In one study of 63 patients treated with antiviral therapy, 40% of patients developed retinal hemorrhages and 44% developed cotton wool spots [48]. Diabetes and hypertension were risk factors for retinopathy [47, 49]. It is important for patients with pre-treatment risk factors for retinopathy to undergo retinal examination prior to treatment, and if any visual changes occur during treatment, to undergo ocular re-evaluation. Antiviral treatment must be halted if retinopathy worsens during therapy.

Ribavirin

Ribavirin is used with interferon to treat hepatitis C. Like interferon, it is associated with several adverse effects. Although the adverse effects from ribavirin appear to be less severe than those from interferon, maintaining ribavirin dose appears more critical to the likelihood of achieving a sustained viral response than sustaining the interferon dose [6•]. Thus, it is still imperative to understand and be able to manage ribavirin-associated complications.

Hematologic Effects

The signature adverse effect of ribavirin is anemia, occurring in up to 30% of treated individuals [5•, 6•]. Ribavirin-related anemia is one the most common reasons for dosage reduction or discontinuation of the drug, resulting in 9% to 22% of patients requiring dosage reduction [5•, 6•]. Anemia can result in persistent fatigue, shortness of breath, and lower quality-of-life scores [12]. Treatment with ribavirin displays a drop in hemoglobin during the first 4 weeks of treatment, followed by stabilization, then normalization after treatment completion [9]. The mechanism of ribavirin-associated hemolytic anemia is unclear, but is believed to be related to impaired antioxidant defenses and red blood cell oxidative damages through its metabolites [51]. The degree of hemolytic anemia is directly related to ribavirin dose, renal function, and perhaps patient age [52, 53]. Recently, ITPA gene variants have been found to be protective of anemia in patients treated with ribavirin [54••].

The definition of anemia can vary. Although anemia may be suggested by the rate of hemoglobin drop, it is commonly defined by an absolute value of less than 10 g/dL [55]. Intervention for ribavirin-induced anemia depends on the rate of hemoglobin decrease, absolute hemoglobin value, comorbidities, and symptoms. Therapeutic options include frequent monitoring, blood transfusion, erythropoietin grown factor, and ribavirin dose modification [6•, 8••, 50••]. The risk of significant anemia can be predicted by hemoglobin trends. For instance, a decrease in hemoglobin of at least of 1.5 g/dL after 2 weeks predicts significant decreases after 4 weeks of therapy [56]. Recognition of impending anemia may prompt small reductions of ribavirin to avoid significant decline in hemoglobin.

There is a discrepancy between the intervention for anemia according to package inserts, and what is often done in clinical practice. The respective package inserts recommend decreasing the ribavirin dose by 200 mg/day when using peginterferon α-2b/ribavirin and by 600 mg/day when using peginterferon α-2a/ribavirin, if hemoglobin decreases to less than 10 g/dL in a patient without cardiac risk factors [13, 14, 55]. The package inserts also recommend termination of ribavirin if the hemoglobin levels decrease below 8.5 g/dL.

Studies have shown erythropoietin can improve hemoglobin values, maintain ribavirin dosage levels, and improve quality of life in patients with symptomatic ribavirin-induced anemia [57]. Despite improved adherence with erythropoietin, no studies have shown that the use of erythropoietin translates to higher sustained viral response. This may be due to the large cohort of treated patients needed to show a beneficial effect. There have been reported cases of antibody-mediated pure red-cell aplasia induced by erythropoietin, which is potentially life-threatening, but resolves with termination of erythropoietin treatment and initiation of danazol [58]. A recent study highlighted the correlation between the magnitude of hemoglobin decline and the likelihood of sustained viral response, and indicated an association between the magnitude of hemoglobin decline and ribavirin exposure [59]. Erythropoietin use in early-onset anemia minimized treatment discontinuation and led to higher sustained viral response rates. However, erythropoietin for anemia after 8 weeks of therapy was not associated with higher sustained viral response rates. Moreover, erythropoietin has been linked to a greater incidence of mortality with its use in ischemic stroke patients [60]. These recent concerns regarding raised risks of thromboembolic events and aplastic anemia with erythropoietin justify the judicious use of this agent.

Other Effects

Other ribavirin-associated complications include nausea and pulmonary, dermatologic, and teratogenic effects. Studies have shown that 25% to 40% of patients complain of nausea [5•, 6•, 12]. However, this symptom can be managed with alterations in the patient’s dietary regimen. More specifically, along with maintaining adequate hydration, patients should avoid acidic, spicy, sweet, or greasy foods. Instead, dietary intake should consist of clear beverages and dry foods (e.g., toast and crackers). If nausea persists after dietary changes, antiemetics may be prescribed.

Ribavirin therapy is often associated with a dry, nonproductive cough, which resolves only upon termination of treatment. Most patients can tolerate this adverse effect, and thus it is not a major cause of dose reductions or treatment termination. However, if the cough becomes productive or other clinical indications are present, a chest radiograph should be considered.

The addition of ribavirin in combination therapy increases the incidence of dermatologic adverse effects. More specifically, one study compared the incidence of skin rash in two groups, one receiving interferon monotherapy and one receiving interferon and ribavirin. Monotherapy resulted in an 8% incidence, whereas combination therapy resulted in 28% incidence [41]. Dermatologic side effects with combination therapy are typified by generalized pruritus, skin xerosis, and eczematiform lesions, which are localized to the extremities. Although ribavirin is shown to increase the incidence of dermatologic conditions when added to interferon treatment, it should be noted that ribavirin alone may cause rash and pruritus. Ribavirin must be discontinued if an acute hypersensitivity reaction develops. However, transient rashes do not require ribavirin treatment interruption [55]. Management entails topical corticosteroids, which may be tapered once signs of inflammation and irritation begin to recede. Preventive measures can be taken, with daily emollient therapy and skin moisturizers to commonly affected areas.

Ribavirin has been associated with significant teratogenic or embryocidal effects in nonhuman animal species exposed to it; therefore, patients must take proper precautions when beginning ribavirin treatment. Moreover, ribavirin therapy, which according to the Food and Drug Administration is pregnancy category X, is contraindicated in pregnant woman and in the male partners of women who are pregnant. It is imperative for patients to avoid pregnancy during ribavirin treatment and for 6 months after treatment completion. It is suggested that two reliable forms of effective contraception be used during this time. Upon cessation of treatment, recovery from ribavirin-induced testicular toxicity was apparent within one or two spermatogenesis cycles. Although human studies are lacking, there is a ribavirin pregnancy registry that enrolls pregnant women who have been directly or indirectly exposed to ribavirin [61]. Although underpowered, the results of a recent registry questioned the association between ribavirin and human teratogenicity [62].

Conclusions

References Conclusions The current standard of care for the treatment of hepatitis C infection involves the use of pegylated interferon and ribavirin. This antiviral combination therapy is associated with several potentially serious adverse effects. Fortunately, pegylated interferon and ribavirin have been available for almost a decade, and most of the adverse effects regarding incidence and time of onset have been defined. The management of these antiviral complications has also been well described, including preventive and empiric strategies. Understanding the limitations of current treatment is essential to assure quality of life and adherence during therapy, and may provide insight to deal with the finer points of future treatment strategies.

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37. Watanabe U, Hashimoto E, Hisamitsu T, et al. The risk factor for development of thyroid disease during interderon-alpha therapy for chonic hepatitis C. Am J. Gastrolenterol. 1994;89:399–403.
38. Wesche B, Jaeckel E, Trautwein C, et al. Induction of autoantibodies to the adrenal cortex and pancreatic islet cells by interferon alpha therapy for chronic hepatitis C. Gut. 2001;48:378–383. doi: 10.1136/gut.48.3.378. [PMC free article] [PubMed] [Cross Ref]
39. Betterle C, Fabris P, Zanchetta R, et al. Autoimmunity against pancreatic islets and other tissues before and after interferon-alpha therapy in patients with hepatitis C virus chronic infection. Diabetes Care. 2000;23:1177–1181. doi: 10.2337/diacare.23.8.1177. [PubMed] [Cross Ref]
40. Fabris P, Betterle C, Greggio NA, et al. Insulin-dependent diabetes mellitus during alpha-interferon therapy for chronic viral hepatitis. J Hepatol. 1998;28:514–517. doi: 10.1016/S0168-8278(98)80328-0. [PubMed] [Cross Ref]
41. McHutchinson JG, Gordon SC, Schiff ER, et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med. 1998;339:1485–92. doi: 10.1056/NEJM199811193392101. [PubMed] [Cross Ref]
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43. Aspinall RJ, Pockros PJ. Review article: the management of side-effects during therapy for hepatitis C. Aliment Pharmacol Ther. 2004;20:917–929. doi: 10.1111/j.1365-2036.2004.02192.x. [PubMed] [Cross Ref]
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46. Weegink CJ, Chamuleau RA, Reesink HW, et al. Development of myasthenia gravis during treatment of chronic hepatitis C with interferon-alpha and ribavirin. J Gastroenterol. 2001;36:723–4. doi: 10.1007/s005350170038. [PubMed] [Cross Ref]
47. Jain K, Lam WC, Waheeb S, et al. Retinopathy in chronic hepatitis C patients during interferon treatment with ribavirin. Br J Ophthalmol. 2001;85:1171–1173. doi: 10.1136/bjo.85.10.1171. [PMC free article] [PubMed] [Cross Ref]
48. Kawano T, Shigehira M, Uto H, et al. Retinal complications during interferon therapy for chronic hepatitis C. Am J Gastroenterol. 1996;91:309–313. [PubMed]
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50. McHutchison JG, Manns MP, Brown RS, Jr, et al. Strategies for managing anemia in hepatitis C patients undergoing antiviral therapy. Am J Gastroenterol. 2007;102(4):880–9. doi: 10.1111/j.1572-0241.2007.01139.x. [PubMed] [Cross Ref]
51. DeFranceschi L, Fattovich G, Turrini F, et al. Hemolytic anemia induced by ribavirin therapy in patients with chronic hepatitic C virus infection: role of membrane oxidative damage. Hepatology. 2000;31:997–1004. doi: 10.1053/he.2000.5789. [PubMed] [Cross Ref]
52. Saab S, Oh MK, Ibrahim AB, et al. Anemia in liver transplant recipients undergoing antiviral treatment for recurrent hepatitis C. Liver Transpl. 2007;13(7):1032–8. doi: 10.1002/lt.21184. [PubMed] [Cross Ref]
53. Nomura H, Tanimoto H, Kajiwara E, et al. Factors contributing to ribavirin-induced anemia. J Gastroenterol Hepatol. 2004;19:1312–7. doi: 10.1111/j.1440-1746.2004.03459.x. [PubMed] [Cross Ref]
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55. Ribavirin [package insert]. South San Francisco, CA: Hoffman-La Roche Inc. 2010.
56. Reau N, Hadziyannis SJ, Messinger D, et al. Early predictors of anemia in patients with hepatitis C genotype 1 treated with peginterferon alfa-2a (40KD) plus ribavirin. Am J Gastroenterol. 2008;103(8):1981–8. doi: 10.1111/j.1572-0241.2008.01957.x. [PMC free article] [PubMed] [Cross Ref]
57. Dieterich DT, Prockros P, Schiff ER, et al.: Interim results of a randomized, double-blind placebo-controlled study demonstrates that epoietin-alfa (PROCRIT) allows maintenance of ribavirin dosing. Hepatology 2002;493.
58. Stravitz RT, Chung H, Sterling RK, et al. Antibody-mediated pure red cell aplasia due to epoetin alfa during antiviral therapy of chronic hepatitis C. Am J Gastroenterol. 2005;100:1415–9. doi: 10.1111/j.1572-0241.2005.41910.x. [PubMed] [Cross Ref]
59. Sulkwski MS, Shiffman ML, Afdhal NH, et al. Hepatitis C virus treatment-related anemia is associated with higher sustained virologic response rate. Gastroenterology. 2010;139(5):1602–11. doi: 10.1053/j.gastro.2010.07.059. [PubMed] [Cross Ref]
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61. Ribavirin Pregnancy Registry. Available at http://ribavirinpregnancyregistry.com/. Accessed September 2010.
62. Roberts SS, Miller RK, Jones JK, et al. The Ribavirin Pregnancy Registry: Findings after 5 years of enrollment, 2003–2009. Birth Defects Res A Clin Mol Teratol. 2010;88:551–9. doi: 10.1002/bdra.20682. [PubMed] [Cross Ref]

Source with thanks: HCV New Drug Research: Adverse Effects: Management of Hepatitis C Antivir...

Questions to the HepC Community (Hepatitis C / Liver Transplant & Biopsy (Hep C) HCV Blog)

2011-04-11T23:20:00.000+01:00

Hi all, still waiting to start tx (treatment) as my HepC nurse and Consultant have had holidays- one straight after the other...bloody frustrating as I want to get cracking.

I have been told that as a (HCV) geno 1a, post (liver) transplant, I only stand a 30% chance of clearing the virus but hey, it’s worth a shot – it might get rid of it or at least knock it back until some new drugs come along – I think it’s gonna be another couple of years before transplant patients get Teleprevir / Boceprevir (new HepC drugs) on the NHS in the UK and I can’t wait that long – Still hanging in there folks!
(Pictured - 'injecting Interferon')

They also said that there is a chance that the HepC treatment drugs, being fairly bloody powerful, could react badly with my immunosuppressant drugs and that I could end up rejecting my new liver - eeek. I suppose if my docs have put me forward tx then they must think its worthwhile...?

Just wondered if any of you within the HepC community had any info on 'pre-dosing' with Ribavarin for a couple of weeks prior to commencing with Interferon?

I have heard of a few people who have done this (geno 1a's like myself) and said it was very successful, especially as they had been non-responders 1st time around and had tried this on their 2nd attempt and WON, any info would be greatly appreciated as been told I am to start tx any time soon .

This is the 1st attempt for me even though HCV took my first liver (my liver was too damaged by the time I was diagnosed with HepC) so anything to improve my chances 'post-transplant' would be good.

I realise also that the jury’s out on this issue as it seems that the people who have 'pre-dosed', highly recommend this action and those that didn’t tend to say ‘stick to yr doctors orders’ – I have to say that I haven’t come across anyone who has 'pre-dosed' and then not achieved the hallowed 'SVR' (Sustained Virological Response - or cured to you and me). If anyone does feel that it’s so contentious an issue that they would rather email me rather than post a comment, then I understand – whether they are for, or against it, I’m trying to get info to make an informed choice.

I also wanted to ask you folks about Anti-Depressants, I was reading an article on HepatitisC NewDrugs (http://goo.gl/fb/v51BG) saying that patients who start treatment from the outset on anti-depressants are far more likely to complete tx than those who don’t. And I wondered if anyone felt they needed pain-killers at any point – I get a lot of abdominal pain but wonder if that’s just because I had a transplant.

Other than that folks all is good and I’m waiting to get on with it, my Hep C Special Nurse rang me to say she has no problem treating me but I have to see the Consultant who got back to work last Friday, once he’s gets to his admin I’ll get an appointment and we should be getting going! Keep everything crossed for me.

Take care everyone… Ian

Tackling Hepatitis C: A Tale of Two Countries (Hepatitis C / Liver Transplant & Biopsy (Hep C) HCV Blog)

2011-04-08T16:52:00.000+01:00

I found this article on the Hepatitis C Trust website and was originally published in The Lancet. As a a Hep C sufferer living in England, it backs up what I have known for some time, having been admitted to my local Hospital twice with symptoms of the virus and misdiagnosed and released thereafter, only for it to be picked up on a blood test done by my GP who didn't accept the hospitals findings. I think this country is in denial of the condition and with 250,000 people suspected of carrying this virus in Britain undetected, it is a disaster waiting to happen!

Hepatitis C remains underdiagnosed and undertreated in parts of the UK. Kelly Morris asks whether the National Liver Strategy for England will deliver what Scotland is already achieving.

20 years after the hepatitis C virus was identified, mortality and hospitalisations are steeply rising in the UK as people infected 20—30 years ago develop end-stage liver disease and hepatocellular carcinoma. At least 250 000 people in the UK might have the infection, mostly undiagnosed, and more likely to present with advanced disease.

Graham Foster, professor of hepatology at Queen Mary's University, London, UK, has “no doubt that more people are being diagnosed with an increase in awareness and testing, but still we are way behind Europe and the rest of the developed world in diagnosing patients and our flow through from diagnosis to treatment is still woefully inadequate”. Foster, who also works as a clinician in east London, tells The Lancet that “treatment services in general are very poor throughout the UK”; he fears that excellent treatment performance and high standards of care are found in few services.

Injection drug use is the main, but not sole risk factor, for contracting hepatitis C, hence the infection is stigmatised and misunderstood in the general population. Prevalence among people who inject drugs is about 50%, yet local provision of testing and treatment varies widely in this often marginalised and unheard of group, despite clear evidence of its usefulness to reduce disease burden and ongoing transmission.

Moreover, treatment and testing are inextricably linked. “If you have a good treatment service, then GPs [general practitioners] become aware that their patients are being cured and that drives them to find the virus and refer patients on”, Foster explains. “If treatment is available at a very low level, GPs stop referring patients because they see nothing happens.” But if specialist services are poorly resourced, then consultants have to place severe restrictions on who gets treatment, he says.

These disparities are increasingly seen now at country level, because action to tackle the virus has widely differed especially between the UK countries Scotland and England, which have similar high prevalence epidemics compared with other countries in the UK and much of the developed world.

England launched a national hepatitis C strategy in 2002 and then an action plan in 2004. This plan, say critics, had few outcome measures, no clear timetable, no attached financing, and the political environment, which focused on priority setting at local National Health Service (NHS) level, was such that the government would not stipulate what was required of local clinical services. “There were absolutely no levers whatsoever to have this actioned. The result is that largely it hasn't been”, says Charles Gore, chief executive officer of the Hepatitis C Trust, which has been campaigning for 10 years for England to develop an actionable plan.

Scotland launched its two-phase action plan in 2006. The 3-year first phase was completed early so that progress and outcomes of the second phase (2008—11) have now been reported for 2 years. From 2007 to 2009, Scotland had a 34% increase in new diagnoses, and a further increase is expected as a consequence of professional and public awareness campaigns, which began early in 2010. Testing has also been enhanced by the roll out of dried blood-spot collection by finger prick, which allows sampling in non-clinical settings.

Development of clinical services has doubled the number of patients started on treatment in 2007—09, while treatment of prison inmates has increased six times. Provision of clean injecting equipment has increased several times since guidelines were approved in 2009. This year, the governance structure and data-generating initiatives now in place will further monitor progress and outcomes. In April, the plan will become part of the Sexual Health and Blood-Borne Virus Framework.

The Scotland Hepatitis C Action Plan “is regarded globally as a model of good practice”, says Gore, who is also president of the World Hepatitis Alliance. To make progress in England, Foster says, Scotland's example “shows how a government-supported initiative can produce enormous dividends in numbers diagnosed and numbers treated”. Gore concurs: “what we in England need to learn is to have outcome measures as a key part of a strategy, to put some money towards it, and to have a clear timetable.” Scotland's total investment in the action plan is about £43 million.

England's action now depends on the forthcoming National Liver Strategy, which is currently in development by the Department of Health and the national clinical director for liver services, Martin Lombard of the Royal Liverpool University Hospital NHS Trust, Liverpool, UK. Lombard has spent the past 12 months working with government policy officials, patient and professional groups, the National Institute for Health and Clinical Excellence, and industry “to develop an understanding of how to tackle the escalating burden of liver disease in England”. Through the strategy, expected in autumn, “we want to transform outcomes for people with liver disease and the various underlying conditions that lead to liver disease”, he says.

Provision of clean injecting equipment has increased in Scotland over the past 2 years

Government commitment to tackling liver disease, including hepatitis, is clear by inclusion of chronic liver disease in outcome frameworks for the NHS and public health, says Lombard, and the National Liver Strategy must link in with the government's vision for the NHS and for public health, published in the white papers Liberating the NHS and Healthy Lives, Healthy People. “Across liver disease, there are significant numbers of patients who need help in their lifestyles to achieve optimum benefit from such a programme. This is an area where we need to do more work with key partners and different agencies”, he says.

“The temptation is going to be to focus very much on alcohol with obesity next as big headline problems”, Gore tells The Lancet. He would like hepatitis C to be the primary focus of strategy: “Out of the main causes of liver disease—alcohol, obesity, and viral hepatitis—hepatitis C is the one bit that is actually solvable in a reasonable amount of time. We could all but eradicate hepatitis C in England within the next 30 years, and make a huge dent in the prevalence in a reasonably short time, if there are clear directions to local NHS on how to go about it in a way that is easy to action.”

Alcohol and obesity must be part of the National Liver Strategy, Foster comments, “but the half million or so people with viral hepatitis deserve a very significant place. There are very large numbers of people infected, the disease burden in terms of cancer and transplantation is huge, and it's a tractable problem where we have solutions”. Conversely, he says, reducing problem drinking requires strategies that are more social than medical, to tackle marketing and availability of alcohol.

Broadly speaking, there is consensus on hepatitis C, “that we need to identify patients earlier”, says Lombard. “Key to this is the need to engage with and up-skill primary and community care services to help us to do this. We also need to do more work with those areas and populations identified as having a higher prevalence of hepatitis C such as drug treatment units, prisons, and within some ethnic groups…many more patients could be treated and prevented from progressing to advanced liver disease if we can achieve this”, he tells The Lancet.

With a new NHS structure and government looking for savings across the board, Gore wonders what will be the levers and incentives to increase testing and treatment. Without safeguards, he says, GP consortia might fail to prioritise or even reduce testing and commissioning of the expensive recommended treatments, with concomitant effects on specialist care. England already ranks second lowest of 14 comparable countries in use of drug treatments, while about a third of patients referred to hospitals in 2009 were not offered treatment, according to the 2010 audit report from the All-Party Parliamentary Hepatology Group and the Hepatitis C Trust.

Amid this uncertainty, the clinical outlook for patients is about to change radically, with the launch of new drugs boceprevir and telaprevir expected within 1 year. When added to existing treatments, these drugs can increase response rates from 40% to 70% in patients with genotype 1 virus and greatly reduce treatment times. “This will transform the picture, both for those who have failed to respond to previous treatment and for naive patients”, says Foster, but could “expose some terrible holes in our service provision”, he warns.

Lombard acknowledges that “some patients who have not responded to treatment programmes in the past may benefit from the availability of newer treatments in the future”. However, he urges, “we need to understand better, and explain better, which particular patients will benefit and what services are needed to treat them”, especially given future financial pressures, and the need to optimise efficiency in services.

Globally, Gore describes the increasing awareness of viral hepatitis B and C infection, as raised last year in a World Health Assembly resolution. July 28 will be the first annual WHO-supported World Hepatitis Day, and WHO is currently drafting a global viral hepatitis strategy. In January, the US Institute of Medicine released a report that recommends steps to improve awareness, recognition, and surveillance, plus integration of care services, to tackle hepatitis B and C in the USA. Foster comments that, “the message from Scotland is absolutely clear. If you set clear targets and you nominate individuals with clear tasks, action happens. If you set rather vague, pious wishes, nothing effective will take place.”

Source: http://www.thelancet.com/ via http://www.hepctrust.org.uk/

Now The Fighting Really Begins...(Hepatitis C / Liver Transplant & Biopsy (Hep C) HCV Blog)

2011-03-25T23:53:00.000+00:00

Okay, so let me tell ya what's been happening of late. I guess it's about time I did as I haven't exactly been a chatterbox recently have I? So I suppose it's about time I put pen to paper so to speak. Truth is, I seem to find it a lot harder to write these days. I don't concentrate as well as I used to and I never was that hot at it even before all this happened - even on my school reports it used to say 'easily distracted, could do better' etc etc. And I find communicating in general a lot more difficult, anyway I'm drifting off the point (and that's something else that was frequently written on my school report!) so let me tell you about whats been going on, 'HepC wise', since I last posted.

A couple of weeks ago, out of the blue, I got a call from one of my doctors at St Jimmy's saying following a discussion by the panel(?); I had been approved to be put forward for Hepatitis C treatment!

Wow, where did that come from? It's true that last month, following my biopsy, that I had asked to be considered for the treatment, but had been told that it would not be considered yet as my doctors were "still trying to protect the graft", it being only a year since my liver transplant and all. They also said that there is a chance that the HepC treatment drugs, being fairly bloody powerful, could react badly with my immunosuppressant drugs and that I could end up rejecting my new liver!

They have been 'messing around' with my immunosuppressant drugs a bit recently, changing me from Neoral Cyclosporin to Rappamune Sirolimus. Not that it worked; my mouth suddenly became a hot bed of ulcers and burned constantly. My tongue swelled up and I was unable to taste anything and inside my mouth became sore and highly sensitive. After a few days I emailed my doc and he rang me back to tell me to stop taking it, revert back to Cyclosporin and that the mouth ulcers were a common side effect of that particular drug. I spent the next week and a half in bed feeling very weak and fevered, waiting for the Sirolimus to work its way out my system. As my doc said, "immunosuppressant drugs are extremely powerful and Sirolimus has a very long 'half life' and it will take time to get rid of it". Great! Looking on the bright side I did lose three-quarters of a stone. However, my doc told me that if I could stand taking it without getting the side effects, the it was the immunosuppressant drug of choice for post liver transplant HepC patients - Clearly, I couldn't stand it!

They had tried the change of drugs as I had been complaining about headaches, especially if I had been pushing or over- exerting myself or I had just gotten over tired and as anybody with HepC knows, fatigue is a major factor of the virus.

Now when I say headaches I mean bloody bad awful headaches, that would leave me locked in a darkened room for two or three days at a time, unable to stand light, loud noise, barely eat and could just about keep myself hydrated by drinking water only. I had been changed from Tacrolimus originally because of these migraine type headaches and they certainly seemed to be less frequent on Cyclosporin but I still got them nevertheless. It looks like for now though, I'm just gonna have to put up with them. It reminds me of the Tommy Cooper joke "Doctor, it hurts when I lift up my arm like this, so the Doctor said 'Don't lift up your arm then'!"

So after emerging from my bedroom with mouth ulcers and headaches in abeyance, I get the phone call from my Doc saying they are putting me forward for HepC treatment, which is good news, even though I face this news with trepidation.

Why trepidation? Well, treatment for HepC is hard work. For a geno 1(a) such as myself (the hardest of all hepatitis C genotypes to get rid of) treatment is generally 48 weeks and can be as long as 72 weeks. The side effects can be bloody awful (I'll post details about it here next post). But probably the hardest of all is that there is no guarantee that it will be successful; at best 50/50 chance of clearing it and following a Liver Transplant, chance of success is down to about 30%.

Not great odds I'm sure you'd agree but what the hell! The thing is, because of the immunosuppressant drugs I take, the HepC virus has a free hand at knackering my new liver so I guess doing everything I can to get rid of it is in my best interest. And if I can't get rid of it, at least I'm gonna give it a good kick in the balls!

My other thought is this, I can feel how the virus is creeping back into my life, day by day, week by week. I can't tell you how much it has affected me as a person. Going back to Tommy Cooper, he used to use a line "I'm a shadow of my former self", talking about how he'd been dieting. The audience would howl with laughter as there was no obvious change to the way he looked and he would stand there with his characteristic 'hapless' look with just the hint of a smile on his face. I feel as though that joke applies very much to me now. Outwardly, it would be difficult to spot that there is anything wrong with me but I am not the confident, 'glass half full' kind of bloke I once was and for me, this is harder to come to terms with than the side effects of any of the drugs I take now or that I face. Above all else, I feel that this change in my being, like the the virus itself, is killing me and that the odds of beating it are low and the challenge ahead is insurmountable. One thing is for sure - now the fighting really begins!

take care everyone... Ian

Stripped Bare by George Monbiot via The Gaurdian

2011-02-15T10:35:00.000+00:00

Hi to all, this is an article written by George Monbiot and published today in The Guardian newspaper - both of whom I have enormous respect for!

Stripped Bare

Shocking new financial manouevres by the British government show who it’s really working for.

By George Monbiot, published in the Guardian 15th February 2011

You think you’ve seen the worst of it; you haven’t. Last week I wrote about how the British government, while imposing extra taxes and devastating cuts on ordinary mortals, has quietly engineered a new tax exemption for the banks and corporations, which also encourages these businesses to shift some of their operations overseas(1). I thought that was as bad as it got. I was wrong.

On the day I wrote that column, the Conservatives were doing something just as repulsive, and far more dangerous. On Wednesday George Osborne told the House of Commons that “we will make sure we learn every lesson that needs to be learnt – so that this [the financial crisis] never happens again”(2). Two days before, his government demonstrated that nothing has been learnt at all. Let me first explain the context.

Most people obtain shares or bonds or other securities in the hope that their value will rise. Short-sellers hope that their price will fall. They might borrow, for example, 10,000 shares and sell them for £1 a piece. Then they pray that the value collapses. If they’re in luck, and the share price halves, they can buy the same number as they sold, for 50p each. They return the shares to the broker who lent them, and pocket £5000 (minus fees).

It’s a controversial practice. Some people say that it helps markets find the right price for their wares. Others maintain that it exacerbates risk, as the sellers are using assets they don’t possess to take on potentially unlimited liabilities (while share prices can’t fall below zero, there is no fixed limit to their increase in value). Short-selling also creates an incentive to try to drive down the price of securities, amplifying or even creating economic crises. An example was the Asian financial crisis of 1997, triggered by a coordinated attack by short-sellers on the Thai baht(3). It destituted tens of millions.

You don’t like the idea? Then take a look at naked short-selling. In this case the sellers not only don’t own the assets they’re selling; they haven’t even borrowed them. They sell a promise of shares, hope the price falls, then try to obtain the shares they’ve sold. In the surreal traditions of modern finance they’re effectively selling securities that don’t yet exist (perhaps they should be called insecurities). Naked shorting may grant short-sellers golden opportunities to wreck companies and economies, by flooding the market with low-cost ghosts.

Almost everyone condemns naked (also known as uncovered) short-selling and wants it banned because of the tremendous risks it presents to the economy. It has already been prohibited in the United States, Japan, Hong Kong, Australia and Brazil(4,5): none of which are renowned for draconian regulation. The European parliament has drafted a directive to bring it to an end within the EU(6). I did say almost everyone, didn’t I? There’s one group frantically seeking to protect naked shorting and strangle the directive: the UK Treasury and Conservative MEPs acting on its instructions.

At a committee meeting in the European parliament last week, the Tory MEP Syed Kamall inveighed against the ban(7). When I asked him how he justified this position, he claimed that ending naked short-selling “will reduce liquidity, meaning that borrowers will insist on higher returns, pushing up the cost of borrowing. This will lead to governments spending more money on servicing debt and less on state-provided public services.”(8) This, as far as I can determine, is rubbish: perhaps the polar opposite of the truth.

Kamall’s office told me his position “reflects that within the government”(9). The Treasury confirmed this: “the UK does not support permanent restrictions on the uncovered short sales of either equities or sovereign debt … we believe it will do much to impair liquidity”(10). Tory MEPs will be instructed by the whips to oppose the ban when they vote on February 28th. The UK Treasury will then oppose it in the European Council.

So here we have a government which claims to have learnt the lessons of the financial crisis, opposing an obvious precaution against insanely risky speculation. How is this possible, when it knows what lax regulation does?

To understand its position, you must first understand that the government is not managing the economy for the people of this nation. It is managing it for a tiny transnational elite, a kind of global gated community. To the people inside the gates, who fund the Conservative party, who own our politics, the media and the banks, the rest of us are an inconvenience, to be bribed, threatened or fooled.

The politicians who get to the top in these circumstances don’t just present no threat to the gated community; they actively do its bidding. That is why Blair succeeded where his Labour predecessors failed. Talent, hard work and intelligence all help, but only if they are harnessed to the interests of economic power.

Governments don’t ask themselves “what can we do that is good for the people?” They ask themselves “how do we persuade people that what we want to do is good for them?” The task of both politicians and the corporate press is to convince us that what is good for billionaires is good for everyone but billionaires. This was the thrust of George Osborne’s statement to the Commons last week(11).

The social isolation of those now in power makes the task easier: they were born into the gated (or moated) economy, and they share its views. Theirs is a different challenge: to disguise their indifference towards the other 99%. They must kiss the babies of the electorate, listen to its complaints, drink its tea – and carry a handkerchief in which to spit. Their interests are not our interests. Their interests are the opposite of ours. If a measure enhances the wealth of the people inside the gates – even if only fleetingly – the government will back it, though it might beggar everyone else. The Treasury’s support of naked short-selling is the homage it pays to naked greed.

An economic war is being fought here. Wealth is being transferred from the poor and middle to the rich at stupefying speed and on a stupefying scale. The financial sector seeks to wring every drop from the productive economy, heedless of the eventual impacts. The government is there to help.

So what do we do? Look to Cairo. I suspect that UK Uncut – the most coherent response so far to the economic transfer – could be the beginning of something very big: a mass citizens’ revolt against institutional theft. The point is not to overthrow the government: that must be done electorally in the UK. The point is to make it impossible to keep fleecing the nation to serve the elite. We go unarmed into this battle; but it’s the government that’s naked.

http://www.monbiot.com/

References:

1. http://www.monbiot.com/2011/02/07/a-corporate-coup-detat/

2. George Osborne, 9th February 2011. Statement on banking by the Chancellor of the Exchequer. http://www.hm-treasury.gov.uk/press_16_11.htm

3. See Joseph Stiglitz, 2002. Globalization and its Discontents. Allen Lane, London.

4. http://www.ft.com/cms/s/0/d2add296-666f-11df-aeb1-00144feab49a.html#axzz1DxOT3Lue

5. http://online.wsj.com/article/SB122518367230175569.html

6. European Commission, 15th September 2010. Proposal for a
Regulation Of The European Parliament And Of The Council on Short Selling and certain aspects of Credit Default Swaps.
http://ec.europa.eu/internal_market/securities/docs/short_selling/20100915_proposal_en.pdf

7. See http://www.europarl.europa.eu/wps-europarl-internet/frd/vod/player?eventCode=20110207-1500-COMMITTEE-ECON&language=en&byLeftMenu=researchcommittee&category=COMMITTEE&format=wmv#anchor1

8. Syed Kamall’s office, pers comm, 14th February 2011. The full email is as follows:

“George – just spoke Syed he is about board a plane now he gave me some new lines for you on the phone,
“If naked short selling of bonds is banned this will reduce liquidity meaning that borrowers will insist on higher returns pushing up the cost of borrowing. This will lead to governments spending more money on servicing debt and less on state-provided public services.”

“A ban on uncovered CDS will mean that investors in infrastructure and other projects, especially in Central & Eastern Europe, will not be able to “insure” their investments by proxy hedging meaning that some projects may not go ahead or they will have to invent new financial instruments to cover their investments that could be less transparent”.”

9. Syed Kamall’s office, pers comm, 14th February 2011.

10. HM Treasury, pers comm, 14th February 2011. The full statement is as follows:

“The UK does not support permanent restrictions on the uncovered short sales of either equities or sovereign debt. No persuasive evidence has been provided to support proposing such restrictions – in terms of either settlement failure or market disorder caused by naked short selling – and we believe it will do much to impair liquidity and increase financing costs for issuers.”

11. George Osborne, 9th February 2011, as above.

Time goes by so slowly...(Hepatitis C / Liver Transplant & Biopsy (Hep C) HCV Blog)

2011-01-31T02:09:00.000+00:00

Well... It just aint been happening for me at the moment folks, which is damn frustrating!

If you haven't already picked it up via twitter or facebook, I didn't get to have my biopsy but just a rather expensive and annoyingly frustrating kind of a week.

As I said on my vid, I was due to go in on Tuesday - Fantastic. So I got up on Tuesday, pumped up and ready to go, dashed around a bit because on that morning I had an interview with a recruitment agency. That went well and as soon as I came out I thought, seeing as I was in town I would do a little retail therapy and hit the shops. I wanted to get myself a wireless internet 'dongle' so that I could keep in touch with the world whilst I was in hospital.

Many of you who have spent time in Hospital will know what I'm talking about when I say I feel so cut-off when I go in to these places, especially for something which you feel is routine or seemingly straight forward and then suddenly turns into a marathon 'staycation'.

If also like me, you use St Jimmy's specialist liver unit, you'll know there are no TV's on the wards. Now I know the phone signal is patchy inside the Hospital but, being a Vodafone customer, I have found that generally speaking I can get a signal. So I headed straight for the Vodafone store and re-emerged 20 minutes later with said item and £20 quid lighter, excellent. Now all I needed was to find was a 'vanilla slice', a cappuccino to go and my retail fix was done, cool!

Ok, once I got home I decided I would put an update on my blog. As my typing is still painfully slow even after all these years of using a keyboard, I decided the quickest way (and as Mandy and the kids were at work and school) was to use Mandy’s' laptop which has a webcam and post a video diary update. (http://youtu.be/vviKROJXEa8)

Ok, so after that I just had to load my 'dongle', pack and soon as we'd had tea and got the kids to bed at 7pm, I would get gone.

The reason for going in the evening before my biopsy was scheduled was to get me into a bed, get some blood taken out of me for tests, put a 'venflon' put in (see image) and then make sure I was 'nil by mouth' from midnight onwards.

Great, so I arrived and everything was going 'swimmingly' until a doctor came round and after 'blowing' a vein in the back of my left hand (not her fault, it's easily done!), we got onto the subject of medications and what drugs I was prescribed. As soon as I told her that I was on Warfarin for a clinical trial, we both realised that having a biopsy was not going to be an option! Goddamit!

I kick myself as I should've realised that taking a drug that thins your blood would probably help you bleed to death when they started trying to 'spike' you to take a peace of your liver away for examination - Warfarin stops your blood from 'clotting'! Ouch! Apparently I should’ve had a letter telling me to stop taking it five days prior to attending. I can only assume that as the study is being carried out by the Imperial College, London and not St James Hospital that it was an oversight and didn’t get sent. This was reaffirmed by the doctor who had no knowledge of my being on the study - bugger.

So after that I was told my bloods would be checked and then could go home in the morning once a new biopsy had been booked. Well, at least I got to check that my dongle worked OK! And I spent the next few hours chatting to guy in the next bed who had recently been 'transplanted' and consequently was still on high doses of meds - he babbled intensely and will probably have no recollection of ever meeting me but I hope I reassured him at the time that he was gonna be OK and was in safe hands. I know his situation only too well!

Next morning I was given a bowl of cornflakes and a cup of insipid tea and informed that my 'bloods' were fine and a date set for the following week to do it all over again! After hanging around to get my venflon taken out, I was released and went down to the main reception. As I'd driven myself in and parked my car in the hospitals' multi storey, I found the pay-parking machine and popped my car parking card in - £15.90!!! Yeas, I'll say that again, 15 bloody ponds, 90! To park overnight for something that didn't happen!!! Bloody Hell, I won't be doing that again.

So after running around the hospital to find a cash-point that worked before the price went up any further, I grabbed a Cappuccino to go to try and get rid of the very bitter taste in my mouth.

So that was last week in a nutshell. I was hoping to get the biopsy out of the way so I could try and make some decisions on moving forward. So many questions at the mo and I can feel the clock ticking away in the background all the while, bloody hell, it's like banging your head against a brick wall sometimes. This damn thing keeps stopping me every time I get started. Ho-Hum, we move on.

I did get some good news; both agencies I had signed on with came back to me with some possibilities of interviews. One fairly well paid but in London (which I'm not opposed to) and one not so but staying here (which is also good). Now I just need biopsy results so I can make a decision on what's best to do!!!

Watch this space, we'll try again this week - I go back in on Tuesday 2nd.

Take care everyone... Ian

My Hepatitis C / Liver Transplant & Biopsy Video Diary

2011-01-25T16:34:00.002+00:00

Hi folks, Just thought I'd post this before for I go back in to Jimmys' for a Liver Biopsy after my 1st year with my new Liver!

happy birthday to me, happy birthday to me....

Take care everyone.... Ian