Mar 31-Hep C Weekend Reading

Happy weekend folks,
Another Saturday is upon us, someone tell me where does the time go.

Each weekend this blog attempts to point the reader to a few inspiring stories, information, healthy tips or medical updates on HCV.

One story I wanted to share with you this weekend can be found on JB Smiths blog, written by Jared Bryan Smith, a man who has overcome addiction, alcoholism, and battled hepatitis C.

In Mr. Smiths newest blog entry Post Interferon Syndrome – Headaches and Celexa (Citalopram) he describes his post-treatment experience with brain fog, headaches, and the reason he made a conscious choice to use Celexa, over opiates.

Mr. Smith has also written his painful memoir, sharing his experience with addiction, family, hepatitis C and the turbulent road to sobriety, titled Hippopotamus Sea: My viral sobriety.

Here is one review of the authors book, click here to read additional reviews.

Jared Bryan Smith with his hippopotamus sea; my viral sobriety transports his readers to a place that most would not dare to go, or wouldn't even think of going.

In excruciating detail, Smith's biographical account details the life of a tragic individual who was bombed out of his mind for seventeen years beginning in his teens until his early thirties when he sought the help of Alcoholic Anonymous (AA). 

What makes this book so powerful and at the same time disturbing is that we know that the narrator is a real person that did in fact live a life of hell as an alcoholic and drug addict, and as he states, "becoming a paranoid delusional nut," who unfortunately has now wound up with Hepatitis C. 

Luckily, Smith has survived the ordeal and is still alive to share his deepest feelings, emotions, experiences, and remorse with his readers. According to Smith, the book has provided him with an opportunity to apologize to some of his friends and relatives, explain to others his behavior, to thank AA that ultimately came to his rescue, and perhaps give hope to other alcoholics and drug addicts.

How can one comprehend a life such as Smith's? To answer that question, we have to look to his early childhood where he was raised in a dysfunctional environment with a father that had succumbed to alcohol and who engendered much agony to his wife and family. At the age of eleven Smith was to experience a traumatic event that would have long lasting repercussions when his father blew his brains out. No doubt, this was probably one of the determining factors in his own downward spiral into self-destruction that expressed itself in his extreme rage and nastiness that lasted for many years thereafter. Quite alarming and disheartening was just before he killed himself, Smith, after receiving a phone call from his dad where he talked about suicide, told him, and as he informs us, he meant it, "why don't you just do us all a favor and kill yourself?"

Throughout his high-school days and into his early thirties Smith was continually lying to himself that everything was just fine when in fact he was living a decadent life jumping from one relationship to another, drinking and drugging himself into a continuous stupor, hallucinating, being fired from one job after another, blaming everyone for his misfortunes, abandoning his son, being arrested several times, and committing the most despicable act in stealing his mother's pain killing medication who was dying from cancer.

A consistent theme among alcoholics and drug abusers is the seeking out of buddies that will share in their drinking and drug habits, and I guess Smith's many relationships with the opposite sex bears this out, as for the most part his female companions were just as messed up as himself. Ironically, through all of this, Smith did manage to secure some great jobs where, when fairly sober, was able to earn a descent salary as an executive recruiter.

Although Smith's memoir is honest and moving, his message would have been much more effective and not have read like a rambling day-by-day journal of the author's life, if there had been better content editing, organization and proofreading. Nonetheless, writing a 355-page painful memoir of a drug addict and alcoholic is not only a cathartic exercise but also quite a daunting task and I commend Smith for his courage and candidness. In the end, hippopotamus sea; my viral sobriety may not exactly be a feel good book, it still left me pulling for Smith and hopefully he has finally found the path to combating his addiction that will eventually lead him to a normal life.
His sobriety, battle against Hepatitis C, and subsequent spiritual awakening is written, first hand for anyone to read, for free if need be, on Books4free.com. or download it on Smashwords for less then a dollar.

For Your Viewing Pleasure

Yesterday I found this uplifting video over at Scope a medical blog published by Stanford University School of Medicine. The video highlights two lovely nurses who sing to their patients. When I was at my fathers bedside following his stroke, I'm not sure I could have made it without his devoted nurse. I LOVE NURSES!

Uploaded by on Mar 29, 2012
Stanford's Marilyn Antipuesto, a nurse's aide, and Mavis Dzadey, RN, were found one morning singing to a semi-conscious patient while caring for him. In this video, Antipuesto and Dzadey explain why they love their jobs and what taking care of patients is really all about.



 In The News

On the topic of inspirational nurses---

Nurse lobbying for hep C treatment changes
A NanaimoPharmaCare coverage for patients suffering from hepatitis C.

Fran Falconer, the mid-Island's only hepatitis support nurse and a volunteer with the non-profit group HepCBC, chaired a public forum in Victoria earlier this month on new treatment guidelines developed by the Canadian Association for the Study of the Liver.

"We hosted the meeting to push the government to make changes," she said.

Hepatitis C is a disease of the liver caused by the hepatitis C virus (HCV). If left untreated or uncured, it can result in end-stage liver failure, leading to organ transplant or death.

Provincial statistics indicate there are about 64,000 British Columbians currently diagnosed with hepatitis C, of whom about 25 per cent have cleared their infection without treatment, much the way people get rid of a flu virus.

HepCBC, a non-profit organization run by and for people infected with or affected by hep C, estimates about 60 per cent of people with the virus will have a long-term infection that causes no problems or causes levels of liver damage ranging from mild to serious.

Falconer said the group already got one of the things it wants – the province announced this week it has approved PharmaCare coverage for a new drug for hep C genotype 1 patients, which is proven to enhance cure rates.

Without coverage, the drug cost patients about $1,000 per week.

Falconer said the next step is to expand PharmaCare coverage to all patients who want treatment and are unable to fight off the virus on their own.

An HCV patient must prove damage to the liver before the province will cover costs of treatment, she said.

"This is a virus that is attacking the liver," said Falconer. "Why are we waiting until there is significant damage? The earlier we treat, the less sick people are, so treatment is more effective."

Treating patients before damage occurs is more cost-effective because caring for patients with health issues resulting from hep C is much more costly, she said.

"An ounce of prevention is worth a pound of cure," said Falconer. "We want equal opportunity for all patients to access care. When people have diabetes, they get treated. Patients with hepatitis C have to qualify."

She also wants more people to get tested – advocates believe there are many people infected who don't know it because they do not have symptoms.

"We call this disease the silent epidemic," said Falconer.

She said intravenous drug users are not the only population at risk – the virus is spread through direct contact with the blood of an infected person and some baby boomers might have been exposed through blood transfusions, tattoos or piercings.

Dr. Paul Hasselback, medical health officer with the Vancouver Island Health Authority, said anyone who received a blood transfusion before 1990 should be tested, as that's when hep C screening began.

He said the health authority is not seeing as many "new" cases as it is finding people who were infected when they were younger – symptoms take years to develop – and in recent years, an average of 80 people per year in Nanaimo are diagnosed.
"There's still probably a significant number who are not aware," said Hasselback.

He said the Canadian Association for the Study of the Liver's new treatment guidelines are a reflection of a better understanding of the hep C virus and the health authority does look at these recommendations, although it is up to the province to make funding decisions.

In an e-mail, the Ministry of Health said the province spends more than $100 million per year on prevention, education and treatment of hepatitis C and because many patients will recover from hepatitis on their own, providing pharmaceutical interventions to all who contract it would result in spending millions more unnecessarily
Related: VICTRELIS™ Now Available for Eligible Patients in British Columbia

Liver Cancer

Commonly used diabetes drug may help to prevent primary liver cancer
Source
Researchers find metformin inhibits fatty acid synthesis, ability of cancer cells to reproduce
Baltimore, MD – March 31, 2012.

Metformin, a drug widely used to treat Type II diabetes, may help to prevent primary liver cancer, researchers at the University of Maryland Marlene and Stewart Greenebaum Cancer Center report in the April 2012 issue of Cancer Prevention Research. Primary liver cancer, or hepatocellular carcinoma, is an often-deadly form of cancer that is on the rise worldwide and is the fastest-growing cause of cancer-related deaths among American men.

Patients with Type II diabetes have a two- to three-fold increased relative risk of developing primary liver cancer. Also at risk are people who are obese, have hepatitis or non-alcoholic fatty liver disease (NAFLD). Metformin, which is derived from the French lilac, is used to treat NAFLD as well as diabetes, and currently is being studied in connection with the prevention of a variety of cancers. This pre-clinical study is the first to focus on liver cancer.

"Our research demonstrated that metformin prevents primary liver cancer in animal models. Mice treated with metformin had significantly smaller and fewer tumors than those who did not receive the medication," says the study's senior author, Geoffrey D. Girnun, Ph.D., assistant professor of biochemistry and molecular biology at the University of Maryland School of Medicine and a research scientist at the University of Maryland Greenebaum Cancer Center. "Based on these findings, we believe metformin should be evaluated as a preventive agent in people who are at high risk. Many patients with diabetes already are taking this medication, with few side effects."

Dr. Girnun adds, "There have been several retrospective epidemiological studies linking metformin with reduced risk of liver cancer, but our study is the first to formally test whether metformin can protect against carcinogenesis – not just tumor growth and development, but actual tumor formation in the liver." He says he will seek federal funding for a clinical trial to study the anti-cancer effects of metformin in patients who have Type II diabetes.

E. Albert Reece, M.D., Ph.D., M.B.A., vice president of medical affairs at the University of Maryland and dean of the University of Maryland School of Medicine, says, "Hepatocellular carcinoma represents a serious public health threat worldwide. With the alarming increases in obesity, Type II diabetes and hepatitis B and C, an even greater number of people will be at risk of developing this cancer in the future. Not only do we need to find more effective treatments, we must also find ways to prevent it. This study conducted by Dr. Girnun and his colleagues is an excellent first step that may ultimately help us to prevent liver cancer in targeted populations."

Kevin J. Cullen, M.D., professor of medicine at the University of Maryland School of Medicine and director of the University of Maryland Greenebaum Cancer Center, says, "This study increases our knowledge of cancer cell metabolism and offers new insights into a possible mechanism for preventing a difficult-to-treat cancer. Translational research is an important focus of our cancer center, and we plan to continue this important area of research as part of a clinical study to determine if there is a possible benefit to patients."

The study is featured on the cover of Cancer Prevention Research, a journal published by the American Association for Cancer Research. Kavita Bhalla, Ph.D., a postdoctoral fellow at the University of Maryland School of Medicine and a Greenebaum Cancer Center research scientist, is the lead author.

Glucose is converted into fatty acids in the liver through a process called lipogenesis. This process is increased in people who have diabetes, hepatitis, fatty liver disease as well as cancer. Dr. Girnun says metformin reduces the level of glucose and inhibits this fatty acid synthesis. "When you block this process, you prevent the cells from making more building blocks to make more cells. There is also no energy to put the building blocks together, and the cells are not able to proliferate, thereby preventing tumors from developing," he explains.

In the study, researchers found that mice treated with metformin in their food developed 57 percent fewer liver tumors than the mice that did not receive the drug; the size of the tumors was reduced by about 37 percent.

About the University of Maryland School of Medicine
Established in 1807, the University of Maryland School of Medicine is the first public medical school in the United States, and the first to institute a residency-training program. The School of Medicine was the founding school of the University of Maryland and today is an integral part of the 11-campus University System of Maryland. On the University of Maryland's Baltimore campus, the School of Medicine serves as the anchor for a large academic health center which aims to provide the best medical education, conduct the most innovative biomedical research and provide the best patient care and community service to Maryland and beyond. www.medschool.umaryland.edu.

About the University of Maryland Marlene and Stewart Greenebaum Cancer Center The University of Maryland Marlene and Stewart Greenebaum Cancer Center is a National Cancer Institute-designated cancer center, which is part of the University of Maryland Medical Center and the University of Maryland School of Medicine. The center is recognized for its active clinical and basic science research program. It has comprehensive programs to treat all types of cancer and is a major referral center for patients throughout Maryland and the region. It is recognized as one of the top 25 cancer centers in the nation by U.S. News and World Report. For more information about the center, go to www.umgcc.org.

Off The Cuff

The placebo effect

Ben Goldacre explains what the placebo effect is and describes its role in medical research and in the pharmaceutical industry.
Source




In Case You Missed It

2012 Newsletter - Special supplement to POZ Magazine on HIV and hepatitis C coinfection



Table of Contents
January 3, 2012

From the Editor
by Tim Horn
The fight against chronic hepatitis C virus (HCV) has reached a long-awaited turning point.
Love Your Liver
by Cindra Feuer
This vital organ works hard for you. Here's how.
Overcoming Adversity
by Reed Vreeland
For Wayne Starks, 51, a former New York City bus driver, overcoming addiction and staying sober have been central to his fight to be healthy while living with both HIV and hepatitis C virus (HCV).
Managing HIV and HCV on the Inside
by Laura Whitehorn
Hep C cases behind bars outstrip those on the street by almost 10 to 1.
Double Trouble
by Benjamin Ryan
A second virus confronts people living with HIV.
Let’s Talk About Sex
by Benjamin Ryan
Recent research suggests that unprotected sex between gay men—especially if they are HIV positive—is promoting hepatitis C transmission in major urban areas across the globe.
Needle Knows
by Tim Horn
If you’re living with HIV and hep C and still using drugs and alcohol, typically the best advice for you is to get clean.
Mr. Coinfection
by Tim Horn
Activist Jules Levin battles for awareness for HIV and hep C
Survivor’s Instinct
by Cristina González
When Lillian Anglada, 53, learned she had hepatitis C, a deep sense of shock set in.
Transplant Trends
by Tim Horn
A little more than a decade ago, there wasn't much hope for HIV-positive people with a failing organ, such as a liver ravaged by hep C-related cirrhosis.
Time for Treatment?
by Benjamin Ryan
The odds of curing hep C are now better than ever.

More information http://www.hepmag.com

Boceprevir, Interferon Alfa-2a, Ribavirin Effective in HCV

 "There is a huge cost difference. Telaprevir, even though it's only [given] for 3 months, is much more expensive than boceprevir. If it wasn't for that, every hepatologist I know would go for telaprevir because it's so much simpler, with a much shorter duration of treatment."

"The reality is, I'm given a budget to treat patients. If I can treat more patients for fewer dollars, I will," said Dr. Aytaman, "That said, I do use both. Most of my patients get boceprevir, but for previous null responders, or if I'm anticipating significant anemia or cytopenia, I go for telaprevir."


From Medscape Medical News > Conference News

Boceprevir, Interferon Alfa-2a, Ribavirin Effective in HCV
Neil Canavan

March 30, 2012 (New York, New York) — Peginterferon alfa-2a, in combination with the protease inhibitor boceprevir and ribavirin (R), was shown to have efficacy equivalent or superior to that seen with historical use of the same regimen with peginterferon alfa-2a — the standard of care — for treating hepatitis C virus (HVC) infection, according to data reported here at the International Conference on Viral Hepatitis (ICVH) 2012.

These results provide a definitive rationale for the inclusion of the alfa-2a interferon variant in the treatment regimen, allowing for greater ease of administration by the patient infected with HCV.
"This is the first trial in which peginterferon alfa-2a was used as a backbone instead of alfa-2b," said study investigator John Howe, PhD, senior principal scientist, Merck & Co., Inc, Whitehouse, New Jersey.
In a previous study of the combination with alfa-2b, the RESPOND-2 (Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2) trial, patients who were previously nonresponders or had relapsed after treatment with ribavirin and interferon alfa-2b showed significant improvement in sustained viral response (SVR) with the addition of boceprevir (66% vs 21% for controls).

The current investigation was a double-blind, placebo-controlled study that randomly assigned 201 HCV genotype-1 relapsers and nonresponders in a 1:2 fashion to 1 of 2 treatment groups. Treatment group 1 received 4 weeks of peginterferon alfa-2a and ribavirin followed by 44 weeks of placebo plus ribavirin plus peginterferon alfa-2a (standard of care). Treatment group 2 received 4 weeks of ribavirin plus peginterferon alfa-2a followed by boceprevir plus ribavirin plus peginterferon alfa-2a for 44 weeks.

Therapy was discontinued in both treatment groups if HCV RNA was undetectable at week 12 (defined as HCV RNA level of 9.3 IU/mL).

Results showed a superior efficacy for the boceprevir combination; 64% of patients achieved an SVR as compared with 21% in the control group (P < .0001).

The rate of relapse with the protease inhibitor combination, 12%, was lower than that with the standard of care, 33% (P value not reported).

"These results are consistent with RESPOND-2," said Dr. Howe.
Reasons for a non-SRV outcome in the boceprevir/peginterferon alfa-2a/ribavirin treatment group for a total of 44 patients were as follows: viral breakthrough on treatment after initially being undetectable for 1 patient; incomplete virologic response for 4 patients; relapse after treatment for 11 patients; and nonresponse for the remaining 28 non-SVR patients (this figure includes patients who discontinued treatment for any reason).

Samples from 33 of 44 patients who received boceprevir/peginterferon alfa-2a/ribavirin who did not achieve SVR were subjected to sequence analysis of postbaseline resistance-associated variants (RAVs). This analysis revealed that 8 of the 33 patients had RAVs; the total included 1 patient with viral breakthrough, 3 patients who had incomplete responses, 2 patients who relapsed, and 2 nonresponders.

By resistance locus, overall RAV profiles were similar to those in all other studies in which peginterferon alfa-2b was used as part of an HCV treatment combination. "The resistance data collected in this trial are consistent with results reported in SPRINT-2 and RESPOND-2," said Dr. Howe.

Treatment Choices With HCV
"I believe that these two interferons [alfa-2a, alfa-2b] are similar," commented Ayse Aytaman, MD, chief of gastroenterology and hepatology, Veterans Affairs New York Harbor Health Care System, Brooklyn, New York. "But we use the alfa-2a more commonly because it's easier for the patient. It is a prepared syringe, you don't have to give weight-based dosing, and it comes in different dosages. It is much simpler. It's particularly good for patients who have trouble understanding instructions."
As for choosing between the 2 new protease inhibitors now at her disposal (boceprevir and telaprevir), "We are trying to learn how to deal with them," she said. "Yes, they are very potent, but they have a lot of side effects."

Before adding interferon on top of a protease inhibitor, Dr. Aytaman cautioned that there are some patients for whom the physician may want to wait for better pharmacologic options before treating.
"When I look at a patient who is 60 years old, I have to consider that I'm going to take a year out of this person's life with them coming to me weekly, or biweekly, injecting himself, being miserable with flu-like symptoms… Why?" Even if the patient has early-stage cirrhotic disease, Dr. Aytaman is willing to wait for an all-oral HCV treatment combination with fewer side effects.

If she has to choose between the protease inhibitors available now, side effect profile is one consideration; cost is another.

"There is a huge cost difference. Telaprevir, even though it's only [given] for 3 months, is much more expensive than boceprevir. If it wasn't for that, every hepatologist I know would go for telaprevir because it's so much simpler, with a much shorter duration of treatment."
"The reality is, I'm given a budget to treat patients. If I can treat more patients for fewer dollars, I will," said Dr. Aytaman, "That said, I do use both. Most of my patients get boceprevir, but for previous null responders, or if I'm anticipating significant anemia or cytopenia, I go for telaprevir."

Dr. Howe is an employee of Merck & Co. Dr. Aytaman has disclosed no relevant financial relationships, and her opinions are expressed as a physician, not as an employee of the US government. 
 
International Conference on Viral Hepatitis (ICVH) 2012. Abstract # 79317. Presented March 26, 2012.

Bristol Myers-Squibb recalls Viaspan over potential Bacillus contamination

 Bristol Myers-Squibb recalls Viaspan over potential Bacillus contamination

The bacterium, Bacillus cereus was found in fluid used to test the sterility of the Viaspan production line. Batches of Viaspan are now being tested for contamination.

Viaspan is a fluid used to preserve organs, primarily the liver, pancreas and bowel, after removal from the donor until transplant into the organ recipient.

Liver patients around the world are once again at risk for a potential disastrous incident involving the bacterium, Bacillus cereus.

The HCV community experienced a similar problem in 2011 with the recall of products tainted with the same bacterium found in prep pads, alcohol swabs, and alcohol swabsticks packaged with pegasys in the U.S . and Pegintron outside the U.S.

MSNBC has continued tracking the tainted wipes, with an update written by JoNel Aleccia on Mar 15.   The complete history of the recall, and involved victims are cataloged at MSNBC.


Bristol Myers-Squibb recalls Viaspan over potential Bacillus contamination
Infectious Disease Examiner
Source

Pharmaceutical giant, Bristol Myers-Squibb (BMS) announced Thursday a global recall of the sterile organ storage fluid, Viaspan after bacterial contamination was discovered on the production line at a manufacturing facility in Austria.

The bacterium, Bacillus cereus as cultivated on sheep blood agar
Credits: 
CDC/ Courtesy of Larry Stauffer, Oregon State Public Health Laboratory

The bacterium, Bacillus cereus was found in fluid used to test the sterility of the Viaspan production line. Batches of Viaspan are now being tested for contamination.

Viaspan is a fluid used to preserve organs, primarily the liver, pancreas and bowel, after removal from the donor until transplant into the organ recipient.

The recall applies to 10 countries where there are alternative storage solutions: Australia, Italy, Estonia, Slovenia, Argentina, Chile, Germany, France, Ireland, and the United Kingdom.

BMS is also working with health officials in 11 other European countries and New Zealand that use Viaspan but do not have alternative solutions.

Viaspan is not sold in the United States or Asia.

The Belfast Telegraph reports that BMS is performing tests to determine where the leak in the production line is located. A faulty pressure gauge is thought to be the problem.

In the UK, where there are about 800 liver, 250 pancreas and 30 to 40 bowel transplants each year, they will continue to use Viaspan as there is currently no evidence of any problems in patients who have recently had transplants where Viaspan has been used according to Chief Medical Officer Professor Dame Sally Davies.

Patients that did present with an infection with Bacillus cereus could be treated with antibiotics.
Bacillus cereus is an aerobic, spore-forming bacterium found in the soil and the environment worldwide.

The organism is a well-recognized and common cause of food poisoning worldwide.
Bacillus cereus made the news last year when alcohol pads produced by the Triad Group were found to be contaminated with the spore-forming bacteria. The contaminated pads were implicated in the death of a 2-year-old boy.

Source:examiner.com

Related: Behind The Headlines: Viaspan organ transplant fluid contamination risk

Lucinda Porter, RN: Hepatitis C Information and Support Group with Book Signing


If you live around or near Redwood City, California then next month you're in for a treat. 

On April 19 from 7:00pm to 8:30pm, Lucinda Porter, RN., the author of Free from Hepatitis C: Your Complete Guide To Hepatitis C will be at the Hepatitis C Information and Support Group in Redwood City, CA discussing the disease.

 It dawns on me that my underdeveloped writing skills hinders my ability to articulate the importance Ms. Porter has had on million plus members of the hepatitis C community.

My gratitude and admiration for the author began over a decade ago after I was diagnosed with the disease. 

For me, Ms. Porter was a curator of hep c knowledge, scavenging the basement archives and organizing the catalog into accessible, easy to understand exhibits. Her early articles helped me negotiate my way through the initial confusion I felt after hearing those three life changing words "You have hepatitis C."  I highly doubt she will ever fully comprehend the impact she had during my decision process of if, or when, I should begin therapy.

As a patient Ms. Porter understands the paralyzing shock and fear experienced after being diagnosed. The next step is inevitable, moving forward searching for information to alleviate that fear. An education process made easier with the help of this accomplished and passionate author.

Please join Lucinda Porter, RN., for her book signing and an evening discussing hepatitis C, at Sequoia Hospital Health and Wellness Center, for more information call (650) 367-5998.

Canada - New Hepatitis C drug approval won't help Gust, but Merck will

Hep C drug approval won't help Gust, but Merck will
By Sarah Simpson, Citizen March 28, 2012
Source Canada.com

The province announced Monday it is expanding Pharmacare coverage for patients suffering from hepatitis C to include the drug boceprevir (Victrelis).

The announcement comes as little relief to Duncan's Shirley Gust, however. The Citizen brought you her story last month. She suffers from chronic hepatitis C - genotype 1 and said though the expensive drug is tailor-made for people with her condition, it still isn't being covered for folks in her particular situation.

"Not for people like me," she said. "It will be people that have got [liver] fibrosis stages two and four and that's it.

"If you are a non-responder and you have compensated cirrhosis or cirrhosis of any kind then they will not fund you."

Gust has compensated liver cirrhosis.

Last month Gust said she feared she would die before the promising drug could possibly cure her.
"My outcome isn't looking good. The quality of life is going down. The outlook is, okay, am I going to be here next year? I'm only 55," she said at the time. "The cirrhosis is getting worse for me. The blood's not pumping through the liver and I'm swelling and the spleen is enlarged. It's getting crucial."
Just when hope seemed to be fading for her, Gust learned of a compassion program run by Victrelis maker Merck.

The problem is, the program was being shut down on March 7. It didn't stop her from applying.
"I slipped in just before March 7," she said. "I haven't got it in my hand yet but as far as I know, I have been approved. I haven't been getting excited quite yet because I haven't seen it in my hand just yet."

When she does receive the drug, which Pharmacare says costs about $1,050 per week, Gust won't be given the standard treatment.

She'll get a 12-week dose of the specialized cocktail of Victrelis and other drugs right off the bat, as opposed to easing into the medicine over a number of weeks and staying on it longer.
"They've never done that before so I'll be kind of like the guinea pig," she said. "They're going to let me have it for 12 weeks and then see what happens."

When added to other medications as part of a treatment program, some Victrelis studies are showing a success rate of 70 to 80 per cent.

"The results are showing that the treatment regime would enable those who have previously failed treatment to now be cured," Renowned epidemiologist Dr. John Farley said last month.
That's the result that Gust, a 55-year-old grandmother of three is desperately hoping for.

Findings Confirm Benefits of Albumin in Treating Cirrhosis Patients Undergoing Large-Volume Paracentesis

KING OF PRUSSIA, Pa., March 28, 2012 /PRNewswire via COMTEX/

Administration of albumin reduces morbidity and mortality in cirrhotic patients undergoing large-volume paracentesis due to severe ascites, according to a new meta-analysis published online today in Hepatology, the official journal of the American Association for the Study of Liver Diseases. Compared with alternative treatments, albumin, a natural plasma-derived protein that expands blood plasma volume, significantly reduced the circulatory dysfunction that often occurs after large-volume paracentesis and also significantly reduced the occurrence of hyponatremia (low blood sodium levels). In addition, risk of death was 36 percent lower in patients receiving albumin than in those receiving other treatments.

"Albumin is the gold standard for preventing circulatory dysfunction following paracentesis greater than five liters. However, other volume expanders as well as vasoconstrictors have been considered as potential alternatives," said Mauro Bernardi, M.D., Professor of Internal Medicine at Bologna University, Bologna, Italy and lead author of the meta-analysis. "Our findings, which combine all the available evidence from randomized clinical trials, confirm that albumin is the best choice for prevention of circulatory dysfunction, and for the first time show decreased incidence of hyponatremia and improved survival with albumin use." 

Within 10 years of receiving a diagnosis, the majority of patients with liver cirrhosis develop ascites, or fluid accumulation in the abdominal cavity. Symptoms include abdominal swelling, major discomfort and impaired breathing often necessitating hospitalization. Patients with ascites have a poor prognosis, with a 50 percent mortality rate over two years. To relieve the pressure caused by the excessive abdominal fluid, a procedure called paracentesis uses a needle to drain the fluid from the abdominal cavity. However, the abrupt removal of large amounts of fluid can worsen existing circulatory dysfunction, leading to a reduction in effective volemia that adversely affect the kidney and other organs. 

The meta-analysis, which included results from 17 randomized clinical trials with 1,225 total patients, found that albumin reduced the risk of post-paracentesis circulatory dysfunction by 61 percent compared with alternative treatments. The analysis also found that the risk of hyponatremia, a condition associated with worsening brain function and death, was decreased 42 percent with albumin administration compared to other treatments, further supporting the well-accepted clinical practice of infusing albumin as the first choice in adjunctive treatment for patients requiring large-volume paracentesis. 

About CSL Behring
CSL Behring is a global leader in the plasma protein biotherapeutics industry. Passionate about improving the quality of patients' lives, CSL Behring manufactures and markets a range of safe and effective plasma-derived and recombinant products and related services. The company's therapies are used in the treatment of immune deficiency disorders, hereditary angioedema, haemophilia, von Willebrand disease, other bleeding disorders and inherited emphysema. Other products are used for the prevention of hemolytic diseases in the newborn, in cardiac surgery, organ transplantation and in the treatment of burns. The company also operates one of the world's largest plasma collection networks, CSL Plasma. CSL Behring is a subsidiary of CSL Limited, a biopharmaceutical company with headquarters in Melbourne, Australia.

For more information, visit www.cslbehring.com .
Contact:Sheila A. Burke, Director, Communications & Public RelationsWorldwide Commercial OperationsCSL Behring610-878-4209 (o)484-919-2618 (c)Sheila.Burke@cslbehring.com 

SOURCE CSL Behring
Copyright (C) 2012 PR Newswire. All rights reserved

Truth and Consequences: The Challenge of Greater Transparency in Liver Distribution and Utilization

Truth and Consequences: The Challenge of Greater Transparency in Liver Distribution and Utilization
K. Washburn1,*, K. Olthoff2
Article first published online: 28 MAR 2012

DOI: 10.1111/j.1600-6143.2011.03960.x
American Journal of Transplantation
Volume 12, Issue 4, pages 799–800, April 2012

© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons

Truth and Consequences: The Challenge of Greater Transparency in Liver Distribution and Utilization


The system for distribution of deceased donor liver allografts has undergone relatively minor modifications over the past 15 years. The local-regional-national algorithm has been modified with small changes for discrete patient groups that impact a minor percentage of the total liver transplant volume. The proliferation of transplant centers has contributed to an entrenchment of the local donation service area as the primary distribution unit, with an amplified level of competition between centers. This has resulted in the relatively infrequent occurrence where a liver is placed nationally with a center outside the region of origin of the donor.

For a liver to make it to the national level of sharing, it must presumably first be denied by centers at the local and regional level. In this issue of American Journal of Transplantation, Lai et al. (1) examine the characteristics of nationally placed livers and the patients that receive them. Several findings are important to highlight. Nationally placed livers comprise 6% of the total transplant volume for the 5-year period. Large proportions (64%) of these nationally placed livers are utilized by just six centers. The MELD score at transplant for the recipients of these organs is significantly lower than that of locally placed livers (20 vs. 24). Fewer patients with hepatocellular cancer (HCC) and other exceptions are transplanted with national livers. After adjusting for a number of donor and recipient variables, the authors conclude that nationally placed livers can be transplanted with no increased risk of patient or graft loss compared to locally placed livers.

We think this study brings to light some important issues in regards to distribution and liver transplantation. Notably, using these less than ideal organs can result in acceptable outcomes in selected patients. In addition, these organs traveled considerably further (528 vs. 26 miles) with a longer cold ischemic time (9 vs. 7 h) than the local organs, without what appears to be significant detrimental consequences, all other things being equal. These results help support the concept that broader distribution of liver allografts is possible without paying a huge penalty in patient outcomes. However, it is important to note there is still a cost. The unadjusted results showed a significantly higher rate of graft loss, and lower patient and graft survival with nationally shared livers. National livers simply are not the same as locally placed livers.

Of interest and pointed out by the authors is the average MELD at transplant is significantly lower in nationally placed livers, with 25% being placed in MELD<15, and fewer recipients had HCC or other exceptions. The authors hypothesize, and we would concur, that it is likely that centers are using these organs in lower MELD score patients who might not otherwise have a chance at transplant, bypassing a large number of patients on their waiting list with presumably higher waitlist mortality, and probably outside the UNOS/OPTN allocation scheme.

These data highlight significant differences in behavior between centers, which cannot be entirely explained by geography. The data indicate that there are just a handful of programs attracting a large percentage of these nationally placed livers. This small group of centers is clearly willing to consider and use livers that others are hesitant to transplant, despite a higher chance of graft loss. It is possible that they feel a great need due to higher waitlist deaths, or perhaps they are more comfortable and better at utilizing these livers than others (2). The authors state they are looking into center specific parameters that may explain some of this behavior. We also do not have the data on other potential downstream outcomes from the use of these livers, such as length of stay, need for dialysis, and other issues associated with poor graft function.

What remains unclear is the process by which these organs are being offered and questions the methods by which these events might be allowed to occur. Are organ procurement organizations (OPO) proceeding systematically through the match run or are they making local and /or regional offers and if no takers moving on to an expedited placement to a center they know will likely accept the offer? If so, is this really a problem as organs are being utilized that otherwise might not be placed. Are other, equally desperate patients being passed over? Or are these OPOs and centers just demonstrating that expedited placement can work?

The system itself (DonorNet) may be inadequate to deal with these unwanted livers. Centers can put broad acceptance criteria in place for offers, and also place a provisional yes, with no obligation or negative consequence to such a response. Yet, multiple affirmative responses can slow down a process to expeditiously place a liver that is not wanted locally. An OPO may move to an expedited placement of a liver by calling a center they are confident will use the liver and obviate the need to go through the entire national list, saving critical minutes. At this time, there is no down side for an OPO to engage in this activity. The problem that we see is that many patients and centers are skipped over with this process. It would be interesting to know in the report from Lai et al. how often this short-circuited process was utilized, and the match list bypassed. OPOs have an incentive to place as many organs as possible for transplant and this system allows them to have “go to” or “speed dial” centers that allow them to maximize their yield. We think the system should be more transparent and fair to patients and centers. Developing a scoring system for centers that use a national liver when they put in a provisional yes may allow more centers to participate in this currently opaque process without slowing it down.

The current report illustrates that it is possible to utilize lower quality organs distributed nationally. The challenge is whether other centers of varying sizes can replicate these results (3), and second, developing a system that is more transparent in how these organs are distributed. Another challenge is to make transplant centers accountable, and to actually abide by the acceptance criteria that they put into DonorNet. The UNOS Liver and Intestine Committee is systematically tackling the issue of expedited placement and distribution with the help of analyses such as Lai et al. Breaking down old paradigms, learning from present experience and challenging our current system may allow the community to move toward a more equitable system for patients.

Disclosure
The opinions expressed here are those of the authors and do not necessarily reflect those of the UNOS Liver and Intestine Committee. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

References
  • Lai JC, Roberts JP, Vittinghoff E, Terrault NA, Feng S. Patient, center, and geographic characteristics of nationally placed livers. Am J Transplant. this issue.
  • 2
    Renz JF, Kin C, Kinkhabwala M, et al. Utilization of extended donor criteria liver allografts maximizes donor use and patient access to liver transplantation. Ann Surg 2005; 242: 556563.
  • 3
    Ozhathil DK, Li YF, Smith JK, et al. Impact of center volume on outcomes of increased-risk liver transplants. Liver Transpl 2011; 17: 11911199.

The AJT Report News and issues that affect organ and tissue transplantation

The AJT Report News and issues that affect organ and tissue transplantation
SUE PONDROM

Article first published online: 28 MAR 2012
DOI: 10.1111/j.1600-6143.2012.04057.x
Download PDF
American Journal of Transplantation
Volume 12, Issue 4, pages 799–800, April 2012


© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons

A Maze of Information
When patients have a choice of transplant centers, how do they make a decision?


Choosing a transplant center can be a confusing and frustrating process for some people. At the initial news that a transplant is needed, an emotional patient may be tongue-tied and not know what questions to ask the doctor. When the shock subsides, the patient may seek more information but not know where to look, or may not understand the plethora of material available online.
 
When individuals have a choice of transplant centers, how do they make that decision? There are no specifi c regulations about the information used to rate center performance. Additionally, the growing numbers of websites vary greatly with regard to the specifi c information that is processed and interpreted.
“There is a general concern about nonmedical websites inappropriately influencing what is arguably the most important medical decision of someone's life,” says Allan Kirk, MD, PhD, professor and scientific director at Atlanta's Emory Transplant Center, and editor-in-chief of the American Journal of Transplantation. “The best site depends on a lot of things that are very difficult to generalize into a rank list. Still, physicians need to make sure they are providing understandable information. Because if they don’t, someone else will.”

Where It Begins

When the patient has the ability to choose his or her transplant center, that choice is tremendously important, says Jesse Schold, PhD, director of outcomes research and clinical epidemiology at the Cleveland Clinic. “There is signifi cant research to suggest that a patient's prognosis is directly related to the center where they are fi rst treated. We showed a few years ago that there is almost a 50% difference in life expectancy for a kidney transplant candidate based on characteristics of the center to which they fi rst go.”1
Choice of a transplant center begins for the patient with transplant information and suggested transplant centers provided by the referring physician. That choice is usually based on geographical location, the referring physician and insurance coverage. Some patients, however, decide to conduct their own research online. Individuals interviewed for this report suggest that physicians and patients should take a careful look at the source of the information provided in these sites.

What's Out There

Many agencies and regulatory bodies provide metrics for quality of care providers. “It's diffi cult to navigate through all of them,” says Dr. Schold. “Often they don't agree on what the high-quality versus low-quality benchmarks are, and they use different metrics to rate hospitals.”

OPTN/UNOS: A comprehensive source of information is provided by the nonprofi t Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) through their patient website http://TransplantLiving.org. Individuals can request free information packets and brochures, including a patient's guide to transplantation, an explanation of organ transplantation and criteria, a list of all U.S. transplant centers, a “snapshot” of the OPTN/UNOS waiting list and a closer look at how to obtain transplant center data.

Keypoints

• When a patient has the freedom to choose his or her transplant center, that choice is tremendously important.
• Patients have access to a great deal of physician and hospital rankings, many of which have vastly different metrics and benchmarks.
• Physicians should be aware of the variety of data available, and ensure they are providing patients with clear, complete information.

SRTR: Another source of data for transplant candidates is the Scientific Registry of Transplant Recipients (SRTR) website, which offers an abundance of information, including comparative data on transplant centers. While these data are the most objective accountings for many relevant metrics, patients can feel intimidated by the site and often are not aware that the SRTR provides a phone advisor who can walk transplant candidates through the abundance of information.

KidneyLink: A relatively new guide for transplant candidates is KidneyLink.org, a free, nonprofit website written by physicians and developed with private donations to the Poly-cystic Kidney Disease Foundation. The site provides a list of questions patients can ask their doctors, a description of tests to expect, tips for how to get on single and multiple waiting lists and more. The information provided for each center (wait-list times, number of patients on the wait list, living- and deceased-donor volume, patient survival rates, etc.) is updated yearly with data from SRTR.

Konnectology: Constantia Petrou, PhD, MBA, founder and CEO of the new, for-profi t service Konnectology.com, says she's found that patients often don't have much time with their doctor, so they go off on their own to research the doctor's recommendations. “That is the point where they get lost,” she says. “They either can't fi nd enough specifi c information to answer their questions, or they fi nd a lot of misinformation out there.”
Launched in December 2011, Konnectology was developed with funding from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDKD). For a fee, Konnectology provides transplant candidates with a list of “best” transplant centers based on the company's methodology, which is described in a study published in the Clinical Journal of the American Society of Nephrology.2 Additionally, the site offers guidelines on how to prepare for evaluation, complete tests, ask specifi c questions of the doctor and transplant staff, and get on a single transplant list or multiple waiting lists.

HealthGrades: HealthGrades is a for-profit (but free to users) source that patients can use to select physicians and hospitals. In November 2011, HealthGrades published a list of transplant hospitals “with the best track record for survival and chances of receiving a donor organ,” according to the company's news re-lease.3 The rankings are based on SRTR data and take into account patient and graft survival outcomes as well as wait-list mortality.

International Transplant Center Data Can Be Hard to Find

No one can argue against patients being informed about transplant center performance and statistics, says Francis Delmonico, MD, president-elect of The Transplantation Society and professor of surgery, Harvard Medical School and Massachusetts General Hospital.
An advisor to the World Health Organization (WHO), Dr. Delmonico says the transparent data available to patients in the U.S. aren't duplicated elsewhere in the world. “For example, the number of living and deceased kidney transplants per million population and by countries is known, but center outcomes are not, ” he says, noting that The Transplantation Society is working with WHO to achieve better transparency about transplant center data worldwide, “but it's a tall order.”

Best Practices

Meanwhile, there are those who wonder if it's at all possible to grade transplant centers, taking into account all the variables. Whatever the case, Dr. Schold believes the transplant community can do a better job in providing tools to help patients navigate the challenging road ahead. Says Amy Hackney, president of the Transplant Financial Coordinators Association, “It is a team effort to present patients with the information to make an informed decision.”

References

Oh, Canada

According to the recent Canadian Institute for Health Information (CIHI) Canadian Organ Replacement Register (CORR) annual report on end-stage organ failure, organ donation rates have stagnated in Canada since 2006.1 Released in February 2012, the report looks at donations between 2001 and 2010 (the most recent year for which data are available).
The living donor rate in 2010 was 16.3 per million population, compared with 17.0 in 2006. The deceased donor rate in 2010 was 13.6 per million population, compared with 14.0 in 2006. All rates were higher than 2001 donations, though.
“We’ve had problems in Canada for some time,” says Philip Halloran, MD, PhD, director of the Alberta Transplant Applied Genomics Centre and founding editor of the American Journal of Transplantation. He blames several groups for failing to advocate for those who need transplants: professionals (including himself), individuals, societies such as the Canadian Society for Transplantation, provincial governments and particularly the federal government— all of whom refuse to face their organ transplantation responsibilities, says Dr. Halloran. “Since we share the same continent with the U.S., there is no good reason for this except the inefficiency of our organizations.”
“In 2008, we were advocating for the Canadian Senate to put in place a Canadian interpretation, under the Canadian constitution, of what the Americans have shown works,” he says. However, that initiative died when the provincial governments chose, instead, for Canadian Blood Services to oversee organ donation.2
Dr. Halloran suggests that Canada needs a national organ transplant act and a national organ transplant agency such as the Organ Procurement and Transplantation Network/United Network for Organ Sharing and the Scientific Registry of Transplant Recipients. “If we could achieve what the Americans are achieving, we could save many lives every year,” he says.


Surgery better than chemoembolization for HCC with portal vein thrombus

Surgery better than chemoembolization for HCC with portal vein thrombus
Last Updated: 2012-03-28 12:44:09 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Patients with hepatocellular carcinoma (HCC) complicated by portal vein tumor thrombus survive longer after resection than after transcatheter arterial chemoembolization (TACE), a retrospective study suggests. 

Median survival was 20 months for the hepatic resection group and 13 months for the TACE group. Overall survival rates were significantly higher for hepatic resection than for TACE at one year (42.0% vs 37.8%, respectively), three years (14.1% vs 7.3%), and five years (11.1% vs 0.5%), with p values for all comparisons <0.001.

The data from 561 men and 42 women with resectable HCC and PVTT were reported by Dr. Min-Shan Chen from Sun Yat-Sen University, Guangzhou, China, and colleagues online February 22 in Cancer.

The cohort included 201 patients who had resection as their initial treatment and 402 matched controls who were treated first with TACE.

According to the paper, the better survival after resection was seen in patients with types I or II PVTT, but not among patients with type III or IV PVTT.

The survival benefit with resection was also limited to patients with a single tumor, especially those with a single tumor larger than five cm.

In multivariate analysis, however, only the type of PVTT and the treatment allocation to resection or TACE were significantly associated with overall survival outcome.

The rate of portal vein invasion in HCC approaches 40%, the authors note.

"Further clinical studies, preferably in the form of prospective randomized trials with adequate sample sizes and prolonged follow-up, are required," the authors note.

"In the absence of such data," they conclude, "surgery is still the standard of care for resectable HCC with PVTT, whereas TACE remains a local therapy option for patients who do not qualify for surgery."

Cancer 2012.

Two Hepatitis C Support Groups Spent Over €250,000 On Trips

Source: The Irish Times  
Thursday, March 29, 2012

PAMELA DUNCAN and MARTIN WALL

TWO SUPPORT groups for people affected by hepatitis C from contaminated blood products spent more than €250,000 on weekends away, golf trips, pool table hire and conferences in 2010, documents released by the HSE reveal.

Transfusion Positive and Positive Action are both funded by the HSE and receive about €860,000 between them annually. However, the HSE recently restricted funding to both organisations and requested them to provide it with information on their accounts for 2010 and 2011.

Documents received by The Irish Times under a Freedom of Information request, which sought correspondence between the HSE and both groups, reveal that Transfusion Positive spent €132,856 on five weekends away for its members and non-infected family members in Ireland in 2010. Transfusion Positive represents men, women and children infected with hepatitis C through contaminated blood products within the State.

The invoices for the money spent show that in the course of these trips, Transfusion Positive included more than €40,000 in complementary therapies, €1,200 in pool table rental, golf trips worth more than €2,000 and €800 spent on band rentals. On a weekend trip to the Connemara Coast Hotel in Furbo, Co Galway, in October last year, 48 members and 89 non-infected family members, including children, as well as 18 therapists and two facilitators, accrued a total cost of over €46,000. This included €350 for 70 water bottles costing €5 each; and 595 towels, the hire of which cost €892.50. Itemised receipts show that over 30 Penneys, Lifestyle Sports and Claire’s Accessories gift cards worth €15 were also invoiced.

The organisation also accrued €23,434 in conference costs for five members who attended two conferences relating to hepatitis C therapies held in Boston and Vienna.

Positive Action submitted €83,625 in expenses relating to weekends away for members and non-infected family members in 2010.

A further €15,548 in invoices relating to the attendance of four executive members at the American Association for the Study of Liver Diseases conference held in Boston last year were also filed with the HSE.

A spokeswoman for Positive Action said: “Positive Action has at all times met all appropriate governance and accountability standards.

“Our budget is agreed in advance with the HSE on an annual basis and our funding has always been used in accordance with the pre-approved budget and under the terms of our finance agreement with the HSE.”

Transfusion Positive said it “has always submitted certified audited accounts to the HSE keeping in mind transparency, governance and probity”. The group said it would be “inappropriate to comment any further at this stage as we are in discussions with the Minister and Department of Health/HSE”.

Hepatitis C virus-specific cellular immune responses in individuals with no evidence of infection

Hepatitis C virus-specific cellular immune responses in individuals with no evidence of infection

Yves Riviere, Thomas Montange, Genevieve Janvier, Caroline Marnata, Ludovic Durrieu, Marie-Laure Chaix, Maria Isaguliants, Odile Launay, Jean-Louis Bresson and Stanislas Pol


For all author emails, please log on.
Virology Journal 2012, 9:76 doi:10.1186/1743-422X-9-76
Published: 28 March 2012

Abstract (provisional)
The detection of hepatitis C virus (HCV)-specific T cell responses in HCV-uninfected, presumably unexposed, subjects could be due to an underestimation of the frequency of spontaneously resolving infections, as most acute HCV infections are clinically silent. To address this hypothesis, HCV-specific cellular immune responses were characterized, in individuals negative for an HCV PCR assay and humoral response, with (n=32) or without (n=33) risk of exposure to HCV. Uninfected volunteers (n=20) with a chronically HCV-infected partner were included as positive controls for potential exposure to HCV and HCV infection, respectively. HCV-specific T cell responses in freshly isolated peripheral blood mononuclear cells were studied ex vivo by ELISPOT and CFSE-based proliferation assays using panels of HCV Core and NS3-derived peptides. A pool of unrelated peptides was used as a negative control, and a peptide mix of human cytomegalovirus, Epstein-Bar virus and Influenza virus as a positive control. Overall, 20% of presumably HCV-uninfected subject tested had detectable T-cell responses to the virus, a rate much higher than previous estimates of HCV prevalence in developed countries. This result would be consistent with unapparent primary HCV infections that either cleared spontaneously or remained undetected by conventional serological assays.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

Video:Dr. Joe Galati Discusses Hepatitis C - Baby Boomers


Uploaded by on Mar 26, 2012
Dr. Joe Galati explained the new research that shows that more baby boomer patients are dying from hepatitis C than those infected with HIV. Anyone born between 1945 and 1965 should have a one time test for hepatitis C, regardless of your risk for hepatitis C. Dr. Galati and Liver Specialists of Texas are located in Houston, in the world famous Texas Medical Center. Dr. Galati is the Medical Director of the Center for Liver Disease and Transplantation at The Methodist Hospital. For more information visit www.texasliver.com, or call 713-794-0700 to make an appointment with Dr. Galati, or to be evaluated for a research study.

MK-5172 : Next-Generation HCV Protease Inhibitor Shows Promise

This coverage is not sanctioned by, nor a part of, the International Association of Physicians in AIDS Care.

Medscape Medical News from the:
International Conference on Viral Hepatitis (ICVH) 2012
March 26 - 27, 2012; New York, New York


Next-Generation HCV Protease Inhibitor Shows Promise
Megan Brooks

March 28, 2012 (New York, New York) — In vitro data on a next-generation hepatitis C virus (HCV) NS3/4A protease inhibitor garnered considerable interest here at the International Conference on Viral Hepatitis 2012.

MK-5172, being developed by Merck & Co, demonstrated "potent activity" against the majority of primary first-generation protease inhibitor resistance-associated variants (RAVs) in biochemical and cell-based phenotype assays, reported Richard J. Barnard, PhD, from Merck & Co.

MK-5172 also inhibited patient-derived NS3 proteases across HCV genotypes and retained activity against HCV proteases isolated from 5 patients with vaniprevir RAVs.

In his presentation, Dr. Barnard noted that virologic failure with first-generation protease inhibitors is often associated with the emergence of RAVs; it is important that next-generation molecules are pangenotypic and active against first-generation protease inhibitor RAVs. "MK-5172 fulfills the profile expected of a next-generation" HCV protease inhibitor, he said.

Douglas T. Dieterich, MD, professor of medicine from the division of liver diseases at Mount Sinai School of Medicine in New York City, who was not involved in the study, told Medscape Medical News that "MK-5172 represents a promising potential best-in-class second-generation protease inhibitor."

"MK-5172 is a truly second-generation protease inhibitor," he explained. "This is really good news for the people who have already failed treatment with a first-generation protease inhibitor."

MK-5172, Dr. Dieterich said, "has activity against the most common resistance mutations caused by telaprevir and boceprevir. Even more encouraging for global use, it is active against genotypes 1, 2, 4, 5, and 6."

Dr. Barnard reports being an employee of Merck & Co and owning stock in the company. Dr. Dieterich reports financial relationships with Bristol-Myers Squibb, Gilead Sciences, Roche Laboratories, and Boehringer Ingelheim. 

International Conference on Viral Hepatitis (ICVH) 2012: Oral Abstract: 79340. Presented March 26, 2012.


Journalist
Megan BrooksMegan Brooks is a freelance writer for Medscape.

Disclosure: Megan Brooks has disclosed no relevant financial relationships.

Related Audio - Oral Abstract: Breakthroughs in Hepatitis
Click Here To Listen
Tuesday, March 06, 2012 9:36 PM

CROI 2012 Seattle - 19th Conference on Retroviruses and Opportunistic Infections: Oral Abstract Sessions

"Moderator" by Juan Berenguer of Hosp Gregorio Maranon, Madrid, Spain
"Moderator" by Sanjay Bhagani of Royal Free Hosp, London, UK

"Tipranavir in Combination with Pegylated Interferon-α-2a+Ribavirin in HCV/HIV-co-infected Patients:  A 24-Week Treatment Interim Analysis" by Douglas Dieterich of Mt Sinai Sch of Med, New York, NY, US

"Boceprevir+Pegylated Interferon+Ribavirin for the Treatment of HCV/HIV-co-infected Patients: End of Treatment (Week 48) Interim Results" by Mark Sulkowski of Johns Hopkins Univ Sch of Med, Baltimore, MD, US

"Evaluation of NS3 Amino Acid Variants in a Phase 1b Study of GT1 Infection with the HCV Protease Inhibitor, MK-5172" by Richard Barnard of Merck & Co, Inc, Whitehouse Station, NJ, US

"The Pharmacokinetic Interactions of HCV Protease Inhibitor TMC435 with Rilpivirine, Tenofovir Disoproxil Fumarate, Efavirenz, or Raltegravir in Healthy Volunteers" by Sivi Ouwerkerk-Mahadevan of Tibotec BVBA, Beerse, Belgium

"Ribavirin Is Needed in Addition to Pegylated Interferon for Optimal Treatment Responses in the Treatment of Acute HCV Genotype 2 and 3 Infection in HIV-co-infected Individuals" by Christoph Boesecke of Univ Hosp Bonn, Germany

"Distinct Motifs in the HCV Poly-U/UC RNA Domain Are Recognized by RIG-I and Trigger Innate Immune Signaling and Governance of HCV/HIV Co-infection" by Gretja Schnell of Univ of Washington, Seattle, US

"Genome-wide Study of Spontaneous Resolution of HCV Infection" by David Thomas of Hepatitis C Spontaneous Resolution Study Consortium, Johns Hopkins Univ, Baltimore, MD, US

"Tenofovir Treatment for =8 Years Results in Pronounced HBsAg Decline in HBeAg+ HIV/HBV-co-infected Patients" by Theodora de Vries-Sluijs of Erasmus Med Ctr, Rotterdam, The Netherlands

"100% Rapid Virologic Response for PSI-7977 + Ribavirin in Genotype 1 Null Responders
(ELECTRON): Early Viral Decline Similar to that Observed in Genotype 1 and Genotype 2/3 Treatment-naïve Patients" by Edward Gane of Auckland City Hosp, New Zealand

View Abstract- CME
International Conference on Viral Hepatitis 2012
MK-5172, a Next Generation HCV NS3/4A Protease Inhibitor is Active against Common Resistance-Associated Variants (RAVs) and Exhibits Cross-Genotype Activity

Hepatitis C Review - Acetaminophen -Tylenol


Hepatitis C Review - Acetaminophen -Tylenol 
 
In 2011 Johnson & Johnson reduced the maximum daily dose of its Extra Strength Tylenol pain reliever, lowering the risk of accidental overdose from the drugs active ingredient acetaminophen.

Today on the blog those label changes are highlighted with the hepatitis C patient in mind. 

What We Know
For the average healthy person acetaminophen-Tylenol is a remarkably safe and effective drug when taken at the recommended dose, yet acetaminophen has caused hundreds of deaths per year.

Why?
 .
The Answer
In November of last year MSNBC author Rachel Rettner wrote an article about a study published in the British Journal of Clinical Pharmacology . The study found that "staggered overdoses" of acetaminophen were more deadly than single overdoses. The journalist explains:

The study looked at what are called "staggered overdoses," in which a person repeatedly exceeds the daily recommendation through small overdoses. This is in contrast to the more familiar single overdose, when a person takes too many pills at once.

In the study, staggered overdoses of acetaminophen  (which is found in Tylenol and other pain reliever's) were more deadly than single overdoses, even though people who experienced staggered overdoses typically took smaller total amounts of acetaminophen than those who experienced a single overdose.
Doctors may not identify staggered overdoses right away, researchers added. People with a staggered overdose may have levels of the drug in their blood below what a standard blood test would indicate as an overdose, even when their liver is badly damaged.

In a related article at TIME  journalist  Maia Szalavitz reported the highest health risks from "staggered overdose" were seen in older people and people who drink a lot of alcohol.

Heavy drinkers and older patients were at highest risk of staggered overdose. Alcohol alone can damage the liver and those who drink more than three drinks a day are advised not to use drugs that contain acetaminophen.
People who misuse opioid painkillers are also at risk of staggered acetaminophen overdose because common opioid drugs like Vicodin include it. While long-term users develop tolerance to the effects of the opioid component of these drugs, this does not affect the potential of acetaminophen to damage the liver.

In  January of 2011 the FDA  asked acetaminophen-manufacturers to lower the strength of acetaminophen in prescription drug products to 325 milligrams per pill. Although, MSNBC reported taking a pill of this dosage every four hours could still put a person at risk from "staggered overdose" from acetaminophen. As noted below Tylenol was not included in the FDA action.
The U.S. Food and Drug Administration (FDA) is asking drug manufacturers to limit the strength of acetaminophen in prescription drug products, which are predominantly combinations of acetaminophen and opioids. This action will limit the amount of acetaminophen in these products to 325 mg per tablet, capsule, or other dosage unit, making these products safer for patients.

In addition, a Boxed Warning highlighting the potential for severe liver injury and a Warning highlighting the potential for allergic reactions (e.g., swelling of the face, mouth, and throat, difficulty breathing, itching, or rash) are being added to the label of all prescription drug products that contain acetaminophen.
These actions will help to reduce the risk of severe liver injury and allergic reactions associated with acetaminophen.

Acetaminophen is widely and effectively used in both prescription and over-the-counter (OTC) products to reduce pain and fever. It is one of the most commonly-used drugs in the United States. Examples of prescription products that contain acetaminophen include hydrocodone with acetaminophen (Vicodin, Lortab), and oxycodone with acetaminophen (Tylox, Percocet).

OTC products containing acetaminophen (e.g., Tylenol) are not affected by this action. Information about the potential for liver injury is already required on the label for OTC products containing acetaminophen. FDA is continuing to evaluate ways to reduce the risk of acetaminophen related liver injury from OTC products. Additional safety measures relating to OTC acetaminophen products will be taken through separate action, such as a rulemaking as part of the ongoing OTC monograph proceeding for internal analgesic drug products.

Acetaminophen-ALT elevations in non-drinkers
I thought this was interesting, in 2010 a study published in "The Journal of Human Pharmacology and Drug Therapy" researchers found that daily use of acetaminophen - at the daily maximum dose of 4 g/day for 10 days causes asymptomatic ALT elevations in non-drinkers.

2010 Study/Full Text:
In conclusion, administration of the maximum daily recommended dose of acetaminophen, 4 g/day to healthy non-drinkers for more than 4 consecutive days is associated with asymptomatic ALT elevation in most subjects. ALT elevations are generally between 1.5 and 2 times their pre-treatment measurements are not accompanied by other laboratory findings or symptoms of liver injury and all ALT elevations resolved once acetaminophen administration was stopped.
 
Hepatitis C And Tylenol

Under the supervision of a doctor, and depending on the condition of the liver, people undergoing HCV therapy are often prescribed Tylenol for joint aches, pain and fever relief, without risk or complications. 
 

Someone please tell me what is the recommended dose of Tylenol is for people with HCV ?
.
The Recommended dose of acetaminophen (Tylenol®) for patients with hepatitis C

According to "The Department of Veterans Affairs" website (updated: July 21, 2011) the maximum recommended dose of acetaminophen (Tylenol®) for patients with hepatitis C is two grams (four 500mg tablets) per day.

Tylenol Label Changes
 
 The Maximum Recommended Dose For "Healthy Patients"

In the fall of 2011 new dosing instructions for TYLENOL were put in place by Johnson & Johnson. The maximum daily dose was changed from 8 pills (4,000 milligrams) per day to 6 pills (3,000 milligrams) per day. The drug company also changed the dosing interval from every 4-6 hours to every 6 hours.

*The 2011 label changes for extra strength Tylenol are listed below, the company says it will cut the maximum dosage of Regular Strength Tylenol and other acetaminophen-containing products in 2012..

* Patients with cirrhosis should avoid pain medications called “non‐steroidal antiinflammatories (NSAIDS)”

Please know with every mention of HCV therapy there are far too many people who have not benefited from new or old drugs that treat this virus. For these people who have advanced liver damage, managing pain or sleep aids can be a daily struggle. Check out the website for an article written by Jennifer Pate, covering the commonly used sleep medications in patients with liver disease
 .
Pain Medications In Patients With Cirrhosis


Medications
Patients with cirrhosis should avoid pain medications called “non‐steroidal antiinflammatories (NSAIDS)”. These include over‐the‐counter medications such as ibuprofen (Motrin, Advil), naprosyn (Aleve), as well as some prescription medications. Ask your doctor if any of your medications are NSAIDS.

For mild to moderate aches and pains, it is safe to use Tylenol (acetaminophen) at doses of 2,000 mg/day or less (no more than 6 regular strength or no more than 4 extra strength each day AND no more than 20 regular strength or no more than 15 extra strength each week). Some cold medicines and prescription pain medicines contain acetaminophen, so read the labels and make sure you don’t
take too much by mistake.

Medications - Decompensated Liver Disease 
A 2011 review article published in the International Journal of Hepatology titled:  

Extra Strength TYLENOL New dosing instructions

Once again the new dosing instructions reduce the maximum daily dose from 8 pills per day to 6 pills per day and change the dosing interval for Extra Strength TYLENOL® from every 4-6 hours to every 6 hours. These labeling changes will be consistent across all single-ingredient Extra Strength TYLENOL® products. We are working closely with other manufacturers of acetaminophen products to help ensure consistency in dosing instructions.

Changes affect the labels of the following Extra Strength TYLENOL® products

Extra Strength TYLENOL® Rapid Release Gels - 500 mg in each gelcap

Extra Strength TYLENOL® Caplets - 500 mg in each tablet

Extra Strength TYLENOL® EZ Tabs - 500 mg in each tablet

Extra Strength TYLENOL® Rapid Blast Liquid - 500 mg in each
15 mL = 1 tablespoon


 *Regular strength Tylenol 

*Consider a lower acetaminophen dose found in regular-strength Tylenol, which is 325 mg. It could be adequate enough to relieve minor pain or treatment side effects.

Regular strength Tylenol - 325 mg in each tablet

Warnings

Regular strength Tylenol

Liver warning:
 
This product contains acetaminophen. Severe liver damage may occur if
  • adult takes more than 12 tablets in 24 hours, which is the maximum daily amount
  • child take more than 5 doses in 24 hours
  • taken with other drugs containing acetaminophen
  • adult has 3 or more alcoholic drinks every day while using this product
Do not use
  • with any other drug containing acetaminophen (prescription or nonprescription). If you are not sure whether a drug contains acetaminophen, ask a doctor or pharmacist
  • if you are allergic to acetaminophen or any of the inactive ingredients in this product
*Ask a doctor before use if the user has liver disease

Extra Strength TYLENOL
 
Caplets, Rapid Release Gels, EZ Tabs

Liver warning:
 
This product contains acetaminophen. The maximum daily dose of this product is 6 caplets, gelcaps, or tablets (3,000 mg) in 24 hours. Severe liver damage may occur if you take
  • more than 4,000 mg of acetaminophen in 24 hours
  • with other drugs containing acetaminophen
  • 3 or more alcoholic drinks every day while using this product
Rapid Blast Liquid

Liver warning:
This product contains acetaminophen. The maximum daily dose of this product is 90 mL (6 TBSP) (3 FL OZ) (3,000 mg) in 24 hours. Severe liver damage may occur if you take
  • more than 4,000 mg of acetaminophen in 24 hours
  • with other drugs containing acetaminophen
  • 3 or more alcoholic drinks every day while using this product
Do not use
  • with any other drug containing acetaminophen (prescription or nonprescription). If you are not sure whether a drug contains acetaminophen, ask a doctor or pharmacist.
  • if you are allergic to acetaminophen or any of the inactive ingredients in this product
****Ask a doctor before use if you have liver disease.

Today, more than 600 over-the-counter and prescription medicines contain acetaminophen.These include medicines to treat symptoms of allergies, cold and flu, and pain with trouble sleeping.

Some people accidentally exceed the recommended dose when taking multiple products at the same time, often without realizing they contain acetaminophen or by not reading and following the dosing instructions. Acetaminophen –the active ingredient in TYLENOL®–is safe when used as directed, but when taken in overdose amounts, it can cause liver damage.

Some Common Medications That Contain Acetaminophen*
It’s important to be aware of the ingredients in all medications that you may be taking. Acetaminophen (APAP) is a common component of many different over-the-counter and prescription medications. You should not take two or more products that contain acetaminophen at the same time.
Taking more than the recommended dose (overdose) of acetaminophen may cause liver damage.

Some Common Prescription Drugs That Contain Acetaminophen*
  • Darvocet®
  • Endocet®
  • Fioricet®
  • Hycotab
  • Hydrocet®
  • Hydrocodone Bitartrate
  • Lortab®
  • Percocet®
  • Phenaphen®
  • Sedapap®
  • Tapanol®
  • Ultracet®
  • Vicodin®
  • Zydone®

Some Common Over-the-Counter Drugs That Contain Acetaminophen*
  • Actifed®
  • Anacin®
  • Benadryl®
  • Cepacol®
  • Contac®
  • Coricidin®
  • Dayquil®
  • Dimetapp®
  • Dristan®
  • Elixir®
  • Excedrin®
  • Feverall®
  • Formula 44®
  • Goody’s® Powders
  • Liquiprin®
  • Midol®
  • Nyquil®
  • Panadol®
  • Robitussin®
  • Saint Joseph® Aspirin-Free
  • Singlet®
  • Sinutab®
  • Sudafed®
  • Theraflu®
  • Triaminic®
  • TYLENOL® Brand Products
  • Vanquish®
  • Vicks®
  • Zicam®
*This is NOT a complete list.

In addition to the new dosing instructions on the OTC label, the makers of TYLENOL® launched Get Relief Responsibly™, an initiative designed to educate consumers about the appropriate use of OTC and prescription medications, particularly those containing acetaminophen, and the importance of reading and following medication labels. As a part of this initiative, the makers of TYLENOL® have created a new website www.getreliefresponsibly.com. The site includes an interactive Acetaminophen Finder tool to help consumers identify products that contain acetaminophen and build a personal acetaminophen medication list to share with their healthcare provider or pharmacist.

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