Two week induction of interferon-beta followed by pegylated interferon alpha-2b and ribavirin for chronic infection with hepatitis C

Hepatol Res. 2010 Jun 8. [Epub ahead of print]

Matsui K, Iwabuchi S, Shimizu H, Yoshida A, Fujikawa T, Takatsuka K.

Center for Digestive and Liver Disease, Ofuna Chuo Hospital, Kanagawa, Japan.

Abstract

Objectives: To elucidate the efficacy of interferon (IFN)-beta induction therapy followed by pegylated IFN alpha and ribavirin for chronic infection with hepatitis C virus (HCV). Methods: Patients chronically infected with HCV genotype 1, high titer were enrolled. Twice daily bolus injections of 3 million units IFN-beta were administered for 14 days. Thereafter, weekly injection of pegylated IFN alpha 2b and daily intake of ribavirin were followed. Therapy duration was adjusted according to the response to the therapy. When time to an undetectable HCV-RNA was 1, 2, 4, 8, and 12 weeks, total duration of therapy was 12, 24, 36, 48 and 60 weeks, respectively. Patients who failed to achieve an undetectable HCV-RNA within 12 weeks discontinued therapy on 12 week. Results: Among the 101 patients treated, 56 (55.4%) achieved sustained virological response (SVR). SVR rate for each treatment duration was 10/10 for 12 weeks, 12/14 for 24 weeks, 18/19 for 36 weeks, 15/26 for 48 weeks, 1/4 for 60 weeks and 0/28 for patients who discontinued therapy at 12 weeks. Mean time to an undetectable HCV-RNA was 35.5 +/- 2.7 days. Mean therapy duration was 27.3 +/- 1.4 weeks. Using a cut off value of 21.5 fmol/L of HCV core-antigen in the first week, SVR could be predicted by sensitivity of 0.91 and specificity of 0.78. Conclusion: IFN-beta induction therapy resulted in acceptable SVR rates despite short therapy duration. Steep reduction of HCV by IFN-beta enables us to predict SVR in the first week of therapy.



PMID: 20557368 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/20557368

Viral response to specifically targeted antiviral therapy for hepatitis C and the implications for treatment success

Can J Gastroenterol. 2010 Jun;24(6):385-90.

Cooper C.

Abstract

Currently, hepatitis C virus (HCV) antiviral therapy is characterized by long duration, a multitude of side effects, difficult administration and suboptimal success; clearly, alternatives are needed. Collectively, specifically targeted antiviral therapy for HCV (STAT-C) molecules achieve rapid viral suppression and very high rapid virological response rates, and improve sustained virological response rates. The attrition rate of agents within this class has been high due to various toxicities. Regardless, several STAT-C molecules are poised to become the standard of care for HCV treatment in the foreseeable future. Optimism must be tempered with concerns related to the rapid development of drug resistance with resulting HCV rebound. Strategies including induction dosing with interferon and ribavirin, use of combination high-potency STAT-C molecules and an intensive emphasis on adherence to HCV antiviral therapy will be critical to the success of this promising advance in HCV therapy.
PMID: 20559582 [PubMed - in process]

http://www.ncbi.nlm.nih.gov/pubmed/20559582

Indian Spice May Delay Liver Damage and Cirrhosis, Study Suggests

ScienceDaily (Mar. 24, 2010) — Curcumin, one of the principal components of the Indian spice turmeric, seems to delay the liver damage that eventually causes cirrhosis, suggests preliminary experimental research in the journal Gut.

Curcumin, which gives turmeric its bright yellow pigment, has long been used in Indian Ayurvedic medicine to treat a wide range of gastrointestinal disorders.

Previous research has indicated that it has anti-inflammatory and antioxidant properties which may be helpful in combating disease.

The research team wanted to find out if curcumin could delay the damage caused by progressive inflammatory conditions of the liver, including primary sclerosing cholangitis and primary biliary cirrhosis.

Both of these conditions, which can be sparked by genetic faults or autoimmune disease, cause the liver's plumbing system of bile ducts to become inflamed, scarred, and blocked. This leads to extensive tissue damage and irreversible and ultimately fatal liver cirrhosis.

The research team analysed tissue and blood samples from mice with chronic liver inflammation before and after adding curcumin to their diet for a period of four and a period of eight weeks.

The results were compared with the equivalent samples from mice with the same condition, but not fed curcumin.

The findings showed that the curcumin diet significantly reduced bile duct blockage and curbed liver cell (hepatocyte) damage and scarring (fibrosis) by interfering with several chemical signalling pathways involved in the inflammatory process.

These effects were clear at both four and eight weeks. No such effects were seen in mice fed a normal diet.

The authors point out that current treatment for inflammatory liver disease involves ursodeoxycholic acid, the long term effects of which remain unclear. The other alternative is a liver transplant.

Curcumin is a natural product, they say, which seems to target several different parts of the inflammatory process, and as such, may therefore offer a very promising treatment in the future.


Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by BMJ-British Medical Journal, via EurekAlert! a service of AAAS.


Journal Reference:

Anna Baghdasaryan, Thierry Claudel, Astrid Kosters, Judith Gumhold, Dagmar Silbert, Andrea Thüringer, Katharina Leski, Peter Fickert, Saul J Karpen, Michael Trauner. Curcumin improves sclerosing cholangitis in Mdr2-/- mice by inhibition of cholangiocyte inflammatory response and portal myofibroblast proliferation. Gut, 2010; 59: 521-530 DOI: 10.1136/gut.2009.186528

http://www.sciencedaily.com/releases/2010/03/100323212150.htm

Understanding the Mechanisms of Liver Regeneration Through Computer Simulation

ScienceDaily (June 9, 2010) — How does the liver manage to regenerate itself even after severe damage? Seeking to find an answer to this significant medical question, scientists of the HepatoSys/German Virtual Liver Network have gained new insights into the underlying processes involved in the regeneration of liver lobules using computer simulation and laboratory experiments.

What that looks like has been demonstrated at the third Conference on Systems Biology of Mammalian Cells (SBMC) from June 3-5, 2010 at the Concert Hall (Konzerthaus) in Freiburg (http://www.sbmc2010.de/). The new perspectives on liver regeneration open the door to developing new treatments for cirrhosis and other injuries to this vital organ.

The singular mechanisms of liver regeneration

The liver is a very special organ: even if more than fifty percent of its overall mass is damaged -- for instance, by intoxication -- it can regenerate itself completely. This amazing ability is essential. The liver is the body's most important metabolic organ and has the task, among others, of detoxifying the blood. To enable it to do this, the liver is equipped with a very complex anatomy: in humans both hepatic lobes are composed of about a million small lobules that are a maximum of one to two millimeters in size.

The blood flowing into the liver enters the lobules via the so-called portal field, which separates neighboring lobules from each other. From there it flows through microvessels surrounded by hepatocytes -- the most common type of cell in the liver -- and drains into a centrally located vein. This special architecture ensures that the blood is brought into optimal contact with the hepatocytes when it flows through the organ.

When a liver has recovered after damage caused by drugs, alcohol consumption or a viral infection, this complex architecture must be restored. The underlying mechanisms are still poorly understood. HepatoSys researchers led by Dirk Drasdo at the Interdisciplinary Centre for Bioinformatics in Leipzig (IZBI) and the French National Institute for Research in Computer Science and Control (INRIA) in Le Chesnay near Paris have started investigating liver regeneration using computer-based methods of systems biology: Drasdo and his team simulated the scenario after intoxication with carbon tetrachloride (CCl4) in mice -- a typical animal model for paracetamol intoxication in humans -- on the computer.

From the tissue section to the computer

The first of three steps was to obtain a computer representation of an average liver lobule. Working closely with the experimental research group led by Jan Hengstler of the Leibniz Institute and the University of Dortmund, the scientists recorded parameters necessary to quantitatively characterize the static lobule architecture, such as the shape and orientation of the blood vessels, and the shape, orientation and spatial organization of the hepatocytes. These parameters were extracted using image processing methods that allow the full three-dimensional reconstruction of microscopic images of specially prepared serial tissue sections, followed by turning the three-dimensional patterns into numbers.

The second step was to record the regeneration process in the liver lobules of mice. The animals were injected with the liver-damaging substance carbon tetrachloride, which -- like paracetamol intoxication -- results in the death of hepatocytes near the central vein of the liver lobule. To characterize the regeneration process quantitatively, the scientists introduced so-called process parameters. These parameters -- also obtained from image analysis -- record when and where new hepatocytes are created and register their movements and alignment within the organ in the process of regenerating the original architecture of the liver lobule.

Finally, based on all these parameters a mathematical model was developed with which the spatial- temporal dynamics of individual hepatocytes and blood vessels could be simulated on a computer. With their computer model the scientists managed to identify previously unrecognized mechanisms during regeneration in liver lobules. As it turned out, the new cells do not just emerge at arbitrary locations within the lobule; "Instead it quickly became evident that the spatio-temporal process can only function properly if the new hepatocytes align themselves along the sinusoids, the micro-blood vessels that traverse the liver lobule," explains Drasdo's co-worker Stefan Höhme. This observation on the basis of the computer model was subsequently confirmed on real liver lobules in a laboratory experiment. "That," according to Höhme, "brings us closer to an understanding of the complex processes involved in liver regeneration."

Not only for the liver

As Drasdo emphasizes, such a dynamic model of a multi-cellular arrangement capable of making correct predictions is still a great exception: "It simultaneously records single cells and the whole tissue," he says. "And that creates the basis for examining in more detail the signalling processes within and among the cells that control regeneration."

The same principle can be applied to build models for other medically relevant questions, e.g. how a tumor spreads to other parts of the body. Understanding these dynamic processes paves the way for new and effective treatments, e.g. to support the liver during the regenerative process or to hinder tumor progression. "Our work was only possible because we were able to work hand in hand with the experimental research group led by Jan Hengstler in Dortmund," emphasized Drasdo, who has many years of experience in modeling cells and cell aggregates. "Only then could we validate the results from our computer simulations directly with an experiment and calibrate our models with experimental data- that is exactly what constitutes systems biology."



Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by HepatoSys/Virtual LIver Network, via AlphaGalileo.


Journal Reference:

S. Hoehme, M. Brulport, A. Bauer, E. Bedawy, W. Schormann, M. Hermes, V. Puppe, R. Gebhardt, S. Zellmer, M. Schwarz, E. Bockamp, T. Timmel, J. G. Hengstler, D. Drasdo. Prediction and validation of cell alignment along microvessels as order principle to restore tissue architecture in liver regeneration. Proceedings of the National Academy of Sciences, 2010; DOI: 10.1073/pnas.0909374107

http://www.sciencedaily.com/releases/2010/06/100607065856.htm

Functional, Transplantable Rat Liver Grafts: Discarded Livers Have Potential to Be Reengineered Into Usable Replacement Organs

ScienceDaily (June 15, 2010) — A team led by researchers from the Center for Engineering in Medicine at Massachusetts General Hospital (MGH) has developed a technique that someday may allow growth of transplantable replacement livers. In a study appearing in Nature Medicine, the investigators describe using the structural tissue of rat livers as scaffolding for the growth of tissue regenerated from liver cells introduced through a novel reseeding process.


"Having the detailed microvasculature of the liver within a biocompatible, natural scaffold is a major advantage to growing liver tissue in a synthetic environment," says Basak Uygun, PhD, research associate at the MGH Center for Engineering in Medicine (MGH-CEM) and the paper's lead author. "Our technique of 'decellularizing' organs leaves the vascular system intact, which facilitates repopulation of the structural matrix and the subsequent survival and function of the introduced liver cells."

Liver transplantation is the only effective treatment for liver failure but is greatly limited by the shortage of donor organs. Each year 4,000 individuals who might have survived with a liver transplant die in the U.S. The shortage of donor livers and other organs is a major force behind the emerging field of tissue engineering and regenerative medicine. Efforts to build tissues from the ground up have not yet approached the goal of transplantable replacement organs, and replacing the liver -- in which each cell is a metabolic factory requiring constant, direct contact with the vascular system -- has been particularly challenging.

The current report describes a refinement of an approach to re-engineering replacement rat hearts that was reported in 2008 by University of Minnesota researchers. Since liver tissue is much more delicate than the muscular structure of the heart, the MGH-CEM team developed a gentler way of flushing living cells out of the liver's structural matrix, which is primarily made of connective tissue like collagen. After the cells were removed, the lobular structure of the liver and its extracellular matrix remained. Containing specific biochemical signals and cues that would direct liver cells to travel to the correct location and resume function -- something quite difficult to replicate using synthetic methods -- the matrix also maintained the organ's intricate network of blood vessels.

Another novel technique was used to reintroduce hepatocytes, the cells that carry out most of the liver's primary functions, into the decellularized matrix. The MGH-CEM approach actually caused cells to penetrate the vascular network and become embedded in the matrix, leaving major vessels clear to carry the essential blood supply. The repopulated matrix displayed normal liver function for up to 10 days in culture, and recellularized grafts were successfully connected to the circulation of live rats with minimal cellular damage and normal hepatocyte function.

"As far as we know, a transplantable liver graft has never been constructed in a laboratory setting before," explains Korkut Uygun, PhD, of the MGH-CEM, the paper's senior author. "Even though this is very exciting and promising, it is a proof-of-concept study only. Much more work will be required to make long-term functional liver grafts that can actually be transplanted into humans. We haven't been able to go beyond several hours in the rats, but it's a great start."

Martin Yarmush, MD, PhD, director of the MGH-CEM and a co-author of the Nature Medicine study, explains that the quarter of a million donor livers discarded each year because they are not suitable for transplantation would be an obvious source of supply for the creation of whole-organ scaffolds. "There is great potential for constructing full-fledged liver lobes containing animal or human cells, but several thorny issues must first be tackled, including formation of a layer of endothelial cells to line graft blood vessels," he says. "Given enough careful work, this approach could ultimately revolutionize tissue engineering and provide real working grafts for the liver and other complex tissues." Yarmush and Korkut Uygun both have faculty appointments at Harvard Medical School.

Additional co-authors of the Nature Medicine report are Alejandro Soto-Gutierrez, MD, PhD, Hiroshi Yagi, MD, Maria-Louisa Izamis, Maria Guzzardi, Carley Shulman, Jack Milwid, Arno Tilles, MD, Francois Berthiaume, PhD, and Yaahov Nahmias, PhD, MGH Center for Engineering in Medicine; Martin Hertl, MD, MGH Surgery; and Naoya Kobyashi, MD, PhD, Okayama University School of Medicine and Dentistry, Japan. The study was partially supported by grants from the National Institutes of Health, National Science Foundation and Shriners Hospitals for Children.


Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Massachusetts General Hospital, via EurekAlert! a service of AAAS.


Journal Reference:

Basak E Uygun, Alejandro Soto-Gutierrez, Hiroshi Yagi, Maria-Louisa Izamis, Maria A Guzzardi, Carley Shulman, Jack Milwid, Naoya Kobayashi, Arno Tilles, Francois Berthiaume, Martin Hertl, Yaakov Nahmias, Martin L Yarmush, Korkut Uygun. Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nature Medicine, 2010; DOI: 10.1038/nm.2170
 
http://www.sciencedaily.com/releases/2010/06/100613181240.htm

A Sport Crafted for Liver Health

Find out the four characteristics of outrigger canoeing that make it a sport with a unique attribute – promoting a healthy liver.

by Nicole Cutler, L.Ac.

Considered the state sport of Hawaii, outrigger canoe racing is an activity with historical roots in Southeast Asia, Polynesia and New Zealand. Over the past few decades, outrigger canoeing has steadily grown in popularity with recreational and competitive clubs strewn across the United States. While paddling an outrigger canoe may not appeal to everyone, this water sport has a number of features that make it ideal for benefiting liver health.

What Is an Outrigger Canoe?
An outrigger canoe is a type of canoe containing one or more outriggers (lateral support floats) fastened to the side of the boat. Some characteristics of this vessel, include:

· Compared to other types of canoes, outrigger canoes can move very fast.

· Most outrigger canoes seat six people, each of whom is important to the boat’s movement.

· Having an attached outrigger increases the canoe’s stability, which reduces its tendency to capsize in rough water.

Besides the canoe itself being unique, an outrigger’s paddling technique also differs from other non-motor powered boats. Different from kayaking or rowing, the outrigger paddle is single-sided, with either a straight or a double-bend shaft. Because there isn’t a dual paddle arrangement, the paddler has to alternate sides often in order to maintain stamina and stability.

Liver Reasons to Paddle
There are several reasons that outrigger canoeing is a great choice for those wanting to support their liver’s health:

1. Cardiovascular Exercise – By preventing or even reversing fatty liver disease, and helping ease portal hypertension, cardiovascular exercise helps people maintain a healthy weight and keeps blood flowing freely throughout the body (including the liver). As a vigorous cardiovascular exercise, outrigger canoeing can burn an estimated 400 calories per hour.

2. Torso Movement – Unlike most sports, outrigger paddling recruits the body’s larger muscle groups in the mid-section – exactly where the liver is housed. Because the strength to power a canoe comes mainly from twisting the torso, there is a great deal of movement in this area. Thus, paddling puts a physical demand on the body’s mid-section, which stimulates the filling and draining of the liver, the natural process necessary for the liver to cleanse the blood.

3. Optimistic Attitude – Besides its associated physical health benefits, paddling in a river, ocean, bay or lake also initiates a positive mental and emotional shift. An active way to appreciate the outdoors, paddling can be peaceful and meditative or it can be exhilarating. In addition, the breaking of the surface tension of water (by waves, falls or a canoe) releases negative hydrogen ions into the atmosphere. One of the many reported health benefits of negative hydrogen ions is to boost serotonin levels, a surefire way to lift one’s mood.

4. No Age Limit – Because it is a low-impact activity with a rich cultural history, outrigger canoeing welcomes people of all ages. Not having an age limit can be important to those who have surpassed 30 years of age and want to get involved in a team sport. In fact, competitive outrigger racing is divided into the following categories: “Open,” which includes those aged 20 to 35 (but is open to any age), “Masters,” which includes those aged 35 to 45, “Senior Masters,” which includes those aged 45 to 55 and “Kapuna,” which includes those aged 55 and up.

Outrigger Tips
If outrigger canoeing might be the sport you are looking for, these two suggestions can help guide you further:

1. Join a Club – The best way to learn about outrigger canoeing is through a local canoe club. Besides learning the proper paddling technique, a club provides the camaraderie inherent to this sport and assures safety issues are addressed.

2. Brush Up On Swimming – Since paddling involves the occasional tip into the water, it is important to be a competent swimmer. If necessary, brush up on your swimming skills so that you can feel confident in a canoe.

If keeping your liver healthy is a priority and group water sports appeals to you, consider outrigger canoeing. Because it is a low-impact cardiovascular exercise, stimulates liver activity by moving the torso, is known to lift the mood and has no age restriction, paddling in an outrigger canoe is an ultimate activity for taking care of your liver.


References:

http://en.wikipedia.org/wiki/Outrigger_canoe , Outrigger Canoe, Retrieved July 31, 2009, Wikimedia Foundation, Inc., 2009.

http://nsmc.staywellsolutionsonline.com/Features/1,2923 , Kayak Your Way to Better Health, Retrieved July 31, 2009, North Shore Medical Center, 2009.

http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Canoeing_and_kayaking?OpenDocument , Canoeing and kayaking - health benefits, Retrieved July 31, 2009, State of Victoria, March 2009.

http://www.health-benefit-of-water.com/negative-ions.html , Water generates Negative Ions, Retrieved August 1, 2009, health-benefit-of-water.com, 2009.

http://www.sheknows.com/articles/7258.htm , Benefits of canoeing and kayaking, Retrieved July 31, 2009, SheKnows LLC, 2009.

http://www.thecancerblog.com/2006/03/08/dragon-boat-races-breast-cancer-survivors-paddle-to-prevention/ , Dragon Boat Races: breast cancer survivors paddle to prevention, Dalene Entenmann, Retrieved July 31, 2009, Weblogs, Inc., 2009.
.
http://www.liversupport.com/wordpress/2010/06/a-sport-crafted-for-liver-health/

Splicing Diversity of the Human OCLN Gene and Its Biological Significance for Hepatitis C Virus Entry

Journal of Virology, July 2010, p. 6987-6994, Vol. 84, No. 14


0022-538X/10/$012.00+0 doi:10.1128/JVI.00196-10

Copyright © 2010, American Society for Microbiology. All Rights Reserved.

Indu Kohaar,1 Alexander Ploss,2 Evgenia Korol,2 Kathy Mu,2 John W. Schoggins,2 Thomas R. O'Brien,3 Charles M. Rice,2 and Ludmila Prokunina-Olsson1*

Laboratory of Translational Genomics,1 Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892,3 Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Diseases, The Rockefeller University, 1230 York Avenue, Box 64, New York, New York 100652

Received 27 January 2010/ Accepted 29 April 2010

Persistent hepatitis C virus (HCV) infection is a primary etiological factor for the development of chronic liver disease, including cirrhosis and cancer. A recent study identified occludin (OCLN), an integral tight junction protein, as one of the key factors for HCV entry into cells. We explored the splicing diversity of OCLN in normal human liver and observed variable expression of alternative splice variants, including two known forms (WT-OCLN and OCLN-ex4del) and six novel forms (OCLN-ex7ext, OCLN-ex3pdel, OCLN-ex3del, OCLN-ex3-4del, OCLN-ex3p-9pdel, and OCLN-ex3p-7pdel). Recombinant protein isoforms WT-OCLN and OCLN-ex7ext, which retained the HCV-interacting MARVEL domain, were expressed on the cell membrane and were permissive for HCV infection in in vitro infectivity assays. All other forms lacked the MARVEL domain, were expressed in the cytoplasm, and were nonpermissive for HCV infection. Additionally, we observed variable expression of OCLN splicing forms across human tissues and cell lines. Our study suggests that the remarkable natural splicing diversity of OCLN might contribute to HCV tissue tropism and possibly modify the outcome of HCV infection in humans. Genetic factors crucial for regulation of OCLN expression and susceptibility to HCV infection remain to be elucidated.

* Corresponding author. Mailing address: Laboratory of Translational Genomics, National Cancer Institute, National Institutes of Health, 8717 Grovemont Circle, Bethesda, MD 20892-4605. Phone: (301) 443-5297. Fax: (301) 443-3234. E-mail: prokuninal@mail.nih.gov


Published ahead of print on 12 May 2010.

Supplemental material for this article may be found at http://jvi.asm.org/ .

Journal of Virology, July 2010, p. 6987-6994, Vol. 84, No. 14

0022-538X/10/$012.00+0 doi:10.1128/JVI.00196-10

Copyright © 2010, American Society for Microbiology. All Rights Reserved
 
http://jvi.asm.org/cgi/content/abstract/84/14/6987?view=short&fp=6987&vol=84&lookupType=volpage

HCV Rapidly Develops Resistance to Directing-acting Agents, Indicating Need for Multidrug Combos

SUMMARY: The hepatitis C virus (HCV) can rapidly develop mutations that confer resistance to multiple direct-acting agents such as HCV protease and polymerase inhibitors, according to a mathematical model described in the May 5, 2010 edition of Science Translational Medicine. Researchers suggested that effective oral therapy without interferon may require as many as 4 complementary drugs to avoid resistance.

Standard therapy for chronic hepatitis C using pegylated interferon plus ribavirin can cause difficult side effects and only clears the virus about half the time, leading researchers to evaluate a large number of direct-acting oral drugs that target specific steps of the viral lifecycle.

But HCV mutates easily and rapidly as it replicates, which allows for emergence of drug resistance mutations. Recent research indicates that resistance mutations are common, and in order for these agents to have prolonged effectiveness without interferon, some people may require "cocktails" of as many as 4 drugs that work in different ways.

Below is the text of a press release issued by the University of Illinois at Chicago summarizing the modeling study.

Combination of Direct Antivirals May Be Key to Curing Hep C

Chicago -- May 5, 2010 -- A combination of antiviral drugs may be needed to combat the drug resistance that rapidly develops in potentially deadly hepatitis C infections, a new study using sophisticated computer and mathematical modeling has shown.

Using probabilistic and viral dynamic models, researchers at the University of Illinois at Chicago, Oakland University and Los Alamos National Laboratory predict why rapid resistance emerges in hepatitis C virus and show that a combination of drugs that can fight three or more mutated strains may be needed to eradicate the virus from the body. They compared their model with data from a clinical trial of the new direct-acting antiviral medication telaprevir.

The findings are published in Science Translational Medicine.

Hepatitis C is a progressive liver disease that can lead to cirrhosis and liver cancer. Current standard treatment is a combination of the antiviral drugs interferon and ribavirin for a period of 24 to 48 weeks -- a regimen that is long and expensive, carries side effects, and is successful only in about half of patients.

Intensive effort has focused on developing direct antiviral drugs. But the virus is genetically diverse, and so may be particularly prone to develop resistance, said Harel Dahari, research assistant professor of hepatology in the UIC College of Medicine and one of the paper's co-authors.

One way to combat resistance would be to administer multiple drugs, each with a different mechanism of inhibiting the virus.

"We found that rapid emergence of resistance to these types of drugs is due to a population of viruses already present, allowing the resistant virus to become the dominant strain," said Dahari.

The researchers suggest that a combination of new antiviral drugs will be needed to fight all of the resistant virus strains and achieve better cure rates for the disease.

"We are moving to a new era where we can treat these patients with direct-acting agents against the virus, in which we specifically target the life-cycle of the virus," Dahari said.

To replace the standard treatment, four or more different types of direct drugs may be needed, Dahari said. However, some patients may need fewer drugs. It depends on the level of the virus in their blood, among other factors.

It is frustrating for patients to go through a long, difficult treatment and know that they might not be cured, said Dr. Scott Cotler, associate professor of medicine at UIC and a hepatologist who treats patients at the University of Illinois Medical Center's Walter Payton Liver Center.

"Patients are looking forward to a day when they don't have to take interferon and ribavirin," said Cotler. "But as we are learning with this study, if we are going to need four different direct drugs, it is going to be awhile before we get there. Now at least we know where the goal line is."

Dahari suggests that future treatment that includes the standard treatment and direct antivirals, such as telaprevir or boceprevir, will be tailored to each patient and that using direct antivirals may also shorten the duration of treatment.

Investigator affiliations: Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM; Department of Mathematics and Statistics and Center for Biomedical Research, Oakland University, Rochester, MI; Department of Medicine, University of Illinois, Chicago, IL.


6/18/10


Source

University of Illinois at Chicago. HCV Rapidly Develops Resistance to Directing-acting Agents Indicating Need for Multidrug Combos. Press release. May 5, 2010.


References

L Rong, H Dahari, RM Ribeiro, and others. Rapid Emergence of Protease Inhibitor Resistance in Hepatitis C Virus. Science Translational Medicine 2(30): 30ra32 (Abstract). May 5, 2010.

DL Wyles and RT Schooley. Rong's Numbers: Accelerating Progress in HCV Therapeutic Research (Editorial). Science Translational Medicine 2(33):33ps25. May 26, 2010.

http://www.hivandhepatitis.com/hep_c/news/2010/0618_2010_b.html

Idenix Begins Proof-of-Concept Study of HCV Protease Inhibitor IDX320

SUMMARY: Idenix Pharmaceuticals announced last week that it has started a 3-day proof-of-concept study of its experimental hepatitis C virus (HCV) protease inhibitor IDX320. As previously reported, researchers presented data at the recent EASL conference showing that IDX320 showed good anti-HCV activity in laboratory studies and had good pharmacokinetic and safety profiles in animals and HCV negative volunteers. If the latest study produces favorable results, the company expects to test IDX320 and its investigational HCV polymerase inhibitor IDX184 as a combination regimen.


Below is an excerpt from a recent Idenix press release describing the drugs and the new study.

Idenix Pharmaceuticals Initiates Proof-of-Concept Study for Protease Inhibitor IDX320 in Hepatitis C Patients

Cambridge, Mass. -- June 10, 2010 -- Idenix Pharmaceuticals, Inc. (Nasdaq: IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today announced that it has initiated a 3-day proof-of-concept study of IDX320, a protease inhibitor for the treatment of hepatitis C virus (HCV) infection, under a Clinical Trial Application (CTA). The study is evaluating IDX320 in treatment-naive hepatitis C genotype 1-infected patients.

"The potent and multi-genotypic activity demonstrated in vitro, as well as the favorable pharmacokinetics observed in healthy volunteers, suggests a promising profile for further development of IDX320," said Jean-Pierre Sommadossi, PhD, chief executive officer of Idenix. "The landscape for combination development in HCV is evolving quickly. Assuming favorable results from the IDX320 proof-of-concept study, we plan to discuss with regulatory agencies a direct-acting antiviral combination strategy with IDX320 and IDX184, our HCV nucleotide polymerase inhibitor."

Douglas Mayers, MD, Idenix's chief medical officer commented, "We are encouraged by the results seen to date with IDX320 and are hopeful that future clinical studies will allow us to continue advancing this program with the ultimate goal of treating a wide range of patients infected with HCV."

The proof-of-concept trial in HCV-infected patients is a Phase I/II randomized, parallel-arm, double-blind, placebo-controlled study evaluating the safety and antiviral activity of IDX320 in treatment-naive adult patients infected with chronic hepatitis C. The study will evaluate four doses of IDX320, ranging from 50 to 400 mg once-per-day, administered for three days. Each cohort of the study will evaluate eight patients randomized six to IDX320 and two to placebo.


About IDX320

IDX320, a macrocyclic HCV protease inhibitor, is an inhibitor of NS3/4A proteases from genotypes 1a, 1b, 2a and 4a (IC50 values from 0.8 to 1.9 nM), as well as from genotype 3a (IC50=23 nM). IDX320 did not inhibit nine tested cellular proteases (IC50 > 10 uM) in vitro, suggesting high selectivity. IDX320 bound tightly to the HCV protease enzyme with a long dissociation half-life (> 9 hours). After single 2 mg/kg oral doses of IDX320 in two animal species, favorable bioavailability and a long plasma half-life were observed, with substantial plasma concentrations 24 hours post dose. Comparable drug exposure was confirmed in healthy volunteers (n=6) receiving a single 200 mg oral dose. Further, no significant in vitro inhibition of human drug metabolizing enzymes, CYP450s and UGT1A1, by IDX320 suggests low potential for drug-drug interactions in patients.


About IDX184

IDX184 is a novel, liver-targeted nucleotide prodrug of 2'-methyl guanosine monophosphate, which includes Idenix's proprietary liver-targeting technology. This technology enables the delivery of nucleoside monophosphate to the liver, leading to the formation of high levels of nucleoside triphosphate, potentially maximizing drug efficacy and limiting systemic side effects with low, once-daily dosing. IDX184 in combination with pegylated interferon and ribavirin has demonstrated a generally favorable safety profile and potent antiviral activity in an ongoing Phase IIa study.


About Idenix

Idenix Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts, is a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases. Idenix's current focus is on the treatment of patients with chronic hepatitis C infection.

For further information about Idenix, please refer to http://www.idenix.com/ .


6/8/10

Source

Idenix Pharmaceuticals. Idenix Pharmaceuticals Initiates Proof-of-Concept Study for Protease Inhibitor IDX320 in Hepatitis C Patients. Press release. June 10, 2010.

http://www.hivandhepatitis.com/hep_c/news/2010/0618_2010_a.html

WHEN GOOD DRUGS DO BAD THINGS

If your organs had a personality, your liver would be the strong, silent type. No matter how hard it works at filtering out toxins like alcohol and drugs, it doesn't complain until it's on the verge of collapse. And when we say drugs, we don't mean the illegal kind. We're talking about the dozens of meds with liver-damage potential. The weight-loss aid called orlistat - aka Xenical and Alli - is the latest med that has to include liver cautions on its label. Luckily for us and you, the liver has a remarkable ability to give itself a makeover. So if you do have a DILI (drug-induced liver injury), stopping the med and treating your liver right - no alcohol, for starters - usually will restore it to health, as long as it was in good shape to begin with. But since the liver isn't a whiner, the trick is to spot the damage before it makes your skin itch and turns your eyeballs yellow, your pee dark and your poop pale. Some DILI-defending tips: Read the fine print. You know those package inserts with the tiny type. Get out your magnifier and read it. Cautions about liver damage will make you more alert to warning signs (below). Don't ignore vague symptoms. Nausea, poor appetite, malaise and just not feeling great - especially shortly after starting a medication - can precede the obvious symptoms. Get the tests. Liver-function tests are advised even before treatment begins with some meds, such as terbinafine (e.g., Lamisil), the nail fungus drug. Don't blow them off.

http://telegraphjournal.canadaeast.com/magazine/article/1090306

Blueberries may benefit people with liver diseases

2010-06-18 15:30:00

Last Updated: 2010-06-18 16:11:33

Washington: A new research indicates that blueberries could provide relief to patients suffering from liver diseases - especially hepatic fibrosis.

A study led by Ming-Liang Cheng, MD, from Department of Infectious Diseases, Guiyang Medical College, Guiyang, presented some data from their research on the effectiveness of blueberries on liver fibrosis induced in laboratory animals.

The study shows that blueberries could reduce liver indices, serum levels of hyaluronic acid and alanine aminotransferase, and increase levels of superoxide dismutase and decrease levels of malondialdehyde in liver homogenates compared with the model group. The stage of hepatic fibrosis was also significantly weakened.

The authors suggest that blueberry consumption is beneficial for hepatic diseases including fibrosis.

The study will be published on June 7, 2010 in the World Journal of Gastroenterology.

http://sify.com/news/blueberries-may-benefit-people-with-liver-diseases-news-international-kgsp4djaeef.html

Improving HCV Response With Insulin Resistance

June 9, 2010

Could insulin resistance be getting in the way of your Hepatitis C treatment? To manage this possible complication, discover why many experts advise prescribing medications to manage insulin resistance in an effort to improve Hepatitis C treatment outcomes.


by Nicole Cutler, L.Ac.

Occurring in up to half of American adults, insulin resistance describes when the body can't properly use insulin to maintain normal blood sugar levels. Unfortunate for those affected, research has consistently shown that those with Hepatitis C infection and insulin resistance are more likely to suffer from liver disease progression. Thus, scientists around the globe have been focusing on how to improve the therapeutic outcome of those with insulin resistance who are battling the Hepatitis C virus.

In their search for a common denominator uniting the growing prevalence of obesity, fatty liver disease, congestive heart failure, high cholesterol, elevated blood pressure and diabetes mellitus, health officials agree that insulin resistance appears to fit the profile. Generalized descriptions of the events that lead to insulin resistance are described below:

· Released by the pancreas, insulin is dispersed into the bloodstream in response to elevated blood sugar (glucose) levels.

· By pushing glucose out of the bloodstream and into the body's cells, insulin keeps blood glucose levels from becoming too elevated and allows cells to convert glucose into energy.

· Insulin-resistant cells do not allow for the proper conversion of glucose into energy, resulting in fatigue.

· This resistance to insulin does not permit glucose to enter the cells but, rather, causes it to accumulate in the blood.

· In an attempt to reduce the glucose levels in the blood, the body signals the pancreas to produce and release even more insulin.

· The cycle of insulin-resistant cells causes even more insulin to be released, resulting in high blood insulin levels, which could potentially develop into Type 2 diabetes mellitus.

Several studies have shown that people with chronic Hepatitis C are more likely to have insulin resistance or diabetes than those without Hepatitis C. In addition, insulin resistance is associated with a poorer response to interferon-based therapy. To manage this complication, many experts advise prescribing medications to manage insulin resistance in an effort to improve Hepatitis C treatment outcomes.

As revealed at the 2008 American Association for the Study of Liver Diseases Meeting and published in the August 2009 edition of Hepatology, Spanish researchers found that metformin improved virologic response when added to Hepatitis C interferon-ribavirin therapy in those with insulin resistance. Also known by one of its brand names Glucophage, metformin is an oral medication that helps lower blood sugar in three ways:

1. It lowers the amount of glucose absorbed from food.

2. It lowers the amount of glucose produced by the liver.

3. It increases the body's response to insulin.

Led by Manuel Romero-Gomez, MD, of Valme University Hospital in Seville, 123 patients with genotype 1 Hepatitis C and insulin resistance [homeostasis model of insulin resistance (HOMA) greater than 2] received standard peginterferon-alpha-2a/ribavirin antiviral therapy plus metformin or matching placebo. After six months, the following was determined:

· 67.4 percent of the metformin group had sustained virologic response compared with 49.1 percent of the placebo group

· 57.7 percent of women in the metformin group had sustained virologic response compared with 28.6 percent of women in the placebo group

While the participants who received triple drug therapy (metformin + pegylated interferon + ribavirin) had a better outcome than those without metformin, women had a more dramatic reduction in their viral levels than men.

Adding metformin to antiviral combination therapy may not be the solution for everyone with insulin resistance and Hepatitis C infection. However, Romero-Gomez's research further confirms that taking steps toward maintaining healthy blood sugar levels hinders liver disease progression and increases the likelihood of beating the Hepatitis C virus.


References:

http://www.healthrenewal.org/nhrblog/?p=67 , Over 50% of Americans Have Insulin Resistance - Do You?, Dr. Patrick Nemecheck, Retrieved November 28, 2009, healthrenewal.org, 2009.

http://www.hivandhepatitis.com/2008icr/aasld/docs/112108_a.html, Therapies to Manage Insulin Resistance Improve Response to Interferon-based Therapy in Chronic Hepatitis C Patients, Liz Highleyman, Retrieved November 28, 2009, hivandhepatitis.com, 2009.

http://www.liversupport.com/wordpress/2007/08/the-natural-supplement-for-metabolic-health/ , The Natural Supplement for Metabolic Health, Nicole Cutler, L.Ac., Retreived November 28, 2009, Natural Wellness, 2009.

http://www.medpagetoday.com/Gastroenterology/Hepatitis/3450 , Fat Gets in the Way of Hepatitis C Therapy, Neil Osterweil, Retrieved November 24, 2009, MedPage Today, LLC, 2009.

http://www.medpagetoday.com/MeetingCoverage/AASLD/11662 , AASLD: Metformin Effective Add-On in HCV Treatment, Charles Bankhead, Retrieved November 24, 2009, MedPage Today, LLC, 2009.

http://www.ncbi.nlm.nih.gov/pubmed/19845037 , Treatment of insulin resistance with metformin in naïve genotype 1 chronic hepatitis C patients receiving peginterferon alfa-2a plus ribavirin, Romero-Gomez M, et al, Retrieved November 25, 2009, Hepatology, August 2009.

http://www.hepatitis-central.com/mt/archives/2010/06/improving_hcv_r.html

Dude, We're running for Beaux and organ donation

Amy Donaldson
sports writer
June 18, 2010 at 9:52 a.m.

Running is hard.

It's also invigorating, refreshing and sometimes you feel so good, it almost feels like flying.

But always, there are moments that test your will, your desire, your determination. Many times you question your sanity.

And that's why taking those steps into the wind, uphill or just for miles and miles is so much easier with someone else in mind.

It is the team aspect that makes the Ragnar Relays unique. Running is a solitary endeavor. The decision to stop is yours. No referee can steal your perfect run. Only your own mind can cheat you.

So when I run I like to do it for someone else. I ran the Wasatch Back the first year the race existed, and I had never run more than a 5K at the time. It changed the way I viewed running, myself and other people. Running in the rain, alone at night, I struggled with quitting for the first time. I couldn't bring myself to give up, however, because of my abnormally upbeat teammates cheering me on. I couldn't let them down.

Every year since, and in most races, I run with someone else in my heart.

This year, our entire team - Dude, Where's My Van? - will run for a man named Beaux. None of us know him very well, but we work with his wife - Lois. What I did know of him was the usual stories colleagues offer about the men who support them, the children that make them smile. I also was recently introduced to his talent for photography. He has a website where he posts his pictures, which are, pure and simply amazing. He has a unique and beautiful perspective on life that manifests itself in his art. (http://reflectivelens.blogspot.com/)

Beaux , 49, is the father of two gorgeous girls. He was told two years ago that he'd need a new liver. After a horrific bicycle accident as a child that required more than a dozen blood transfusions, he developed Hepatitis C. He didn't know it until constant stomach aches sent him to the doctors.

Lois recently told us he'd been moved up the transplant list - a moment that gives a family hope and brings home the gravity of the diagnosis.

I was nervous about asking Lois if this group of very marginal athletes could run in her husband's honor and in hopes of raising awareness about organ donation. I mean, if you get the chance to be represented, you want it to be the person who wins. You want to have your name on Lance Armstrong's shirt, not Amy "the queen of shuffling" Donaldson's race bib.
He didn't just say yes. He was as honored to have us represent him as we are to run in his name.

He wrote a beautiful blog about our offer and his feelings, which I hope you visit.

Blog: The Paradox Syndrome

Post: Ragnar Relay's Wasatch Back

Link: theparadoxsyndrome.blogspot.com

And then I hope you take some time to consider organ donation. I know of another friend whose husband is waiting for kidneys. If you have the opportunity to offer life to a stranger, please take it. It is one last gesture of love that we can offer as members of the only team that really counts.

http://www.deseretnews.com/blog/68/10009307/Reasons-to-Run-Dude-Were-running-for-Beaux-and-organ-donation.html

EASL 45th Annual Meeting

EASL 45th Annual Meeting

(European Association for the Study of the Liver)
April 14-18, 2010

Vienna, Austria

Source: NATAP

• New HCV Drugs EASL 2010
• From Ash To Cure - EASL April 14-18 2010
• ANTIVIRAL ACTIVITY, COMBINATION AND RESISTANCE OF ACH-1625, A POTENT HCV NS3 PROTEASE INHIBITOR
• CHARACTERIZATION OF THE HEPATOSELECTIVE DISTRIBUTION OF ACH-1625: A POTENT, CLINICAL STAGE HCV NS3 PROTEASE INHIBITOR
• VIROLOGICAL RESPONSE, SAFETY, AND PHARMACOKINETIC PROFILE FOLLOWING SINGLE - AND MULTIPLE-DOSE ADMINISTRATION OF ACH-1625 PROTEASE INHIBITOR TO HEALTHY VOLUNTEERS AND HCV GENOTYPE-1 PATIENTS
• Validation of the GeneSeq HCV NS5B Sequencing Assay for Patient-Derived HCV Subtypes 1a and 1b
• Resistance Profile Of ABT-333 And Relationship To Viral Load Decrease In Patients Treated In Combination With Peg-interferon And Ribavirin For 28 Days
• Pharmacokinetics of the HCV Polymerase Inhibitor ABT-333 in US and Japanese Healthy Volunteers
• Exposure-Viral Response Analyses of the Non-nucleoside Polymerase Inhibitor ABT-333, Following Monotherapy and ABT-333 Plus Pegylated Interferon and Ribavirin Therapy
• Pharmacokinetics of the HCV Polymerase Inhibitor ABT-072 Following Single and Multiple Dosing in Healthy Adult Volunteers
• Virologic Response Rates Following 4 Weeks of Filibuvir in Combination with Pegylated Interferon Alfa-2a and Ribavirin in Chronically-Infected HCV Genotype-1 Patients
• Genotypic Characterisation of Filibuvir Resistance in Patients Receiving Four Weeks Co-administration of Filibuvir with pegIFN/RBV(12 Week Analysis)
• Exposure-response Relationship of Filibuvir in HCV-infected Patients: Application to Dose Selection for Combination Therapy
• Impact of Sustained Virological Response After Antiviral Treatment in Chronic Hepatitis C Patients on Life Expectancy and Quality-adjusted Life-years
• Locteron, controlled-release interferon alpha 2b, 3 studies at EASL 2010 Vienna - 3 company press releases
• PHASE IIB STUDY OF BALAPIRAVIR (RG1626; NUCLEOSIDE ANALOGUE INHIBITOR OF HCV POLYMERASE) PLUS PEGINTERFERON ALFA-2A (40KD) AND RIBAVIRIN FOR CHRONIC HEPATITIS C GENOTYPE 1: FINAL RESULTS
• RANDOMIZED, OPEN-LABEL, 12-WEEK COMPARISON OF CONTROLLED-RELEASE INTERFERON ALPHA2B + RIBAVRIN VS. PEGYLATED-INTERFERON ALPHA2B + RIBAVRIN IN TREATMENT-NAïVE GENOTYPE1 HEPATITIS C: 4 WEEK RESULTS FROM 480STUDY (PANEL A)
• Slow Responders Benefit From 72 Weeks Peg/Rbv - Predicting Treatment Outcome Among Slow Responders: A Retrospective Analysis of the SUCCESS Study
• Q2week Controlled Release Interferon Alpha2b + Ribavrin Reduces Flu-like Symptoms >50% And Provides Equivalent Efficacy In Comparison To Weekly Pegylated Interferon Alpha2b + Ribavirin In Treatment-naïve Genotype-1 Chronic Hepatitis C: Results From EMPOWER, A Randomized Open-label 12-week Comparison In 133 Patients
• Early Viral Response Of Controlled-release Interferon Alpha2b And Ribavirin Vs. Pegylated-interferon Alpha2b And Ribavirin In Treatment-naïve Genotype-1 Hepatitis C: 12 Week Results (SELECT-2 Trial)
• IMPACT OF LOW-DOSE RITONAVIR BOOSTING ON THE PHARMACOKINETICS OF DANOPREVIR (RG7227; ITMN-191), A HIGHLY POTENT AND SELECTIVE INHIBITOR OF THE HCV NS3/4A PROTEASE
• High Dose Pegasys/rbv can improve SVR: Impact of higher doses of peginterferon alfa-2a and ribavirin on RVR, cEVR and SVR in HCV G1 patients with viral loads ≥400 000 IU/mL weighing ≥85 kg
• Predictors of relapse among patients treated with standard- or induction-dose peginterferon alfa-2a (40KD) combined with standard- or higher-dose ribavirin in difficult-to-cure patients
• Pegasys vs Pegintron, Baseline characteristics and on-treatment predictors of responses from real-world patient cohorts: interim results of the multinational PROPHESYS cohorts
• Metabolic Syndrome (MS) [glucose/diabetes] Is a Negative Predictor of Treatment Outcome in Patients With Chronic Hepatitis C: Results From the IDEAL Study
• Improved Inflammatory Activity With Low-Dose PegIntron (PEG) Maintenance Therapy in Prior Nonresponders With METAVIR Fibrosis Scores (MFS) of F2/F3: Final Results From the EPIC3 Program
• Characterization of resistant mutants selected in vitro by the HCV NS3/4A protease inhibitor BI 201335
• Preclinical characterization of non-covalent HCV NS3/4A protease inhibitor BI 201335
• HBsAg Kinetics of Decay and Baseline Characteristics of HBeAg-Positive Patients with Chronic Hepatitis B Following 3 Years of Tenofovir Disoproxil Fumarate (TDF) Treatment
• Evaluation of Potential Virologic Resistance in HBV Polymerase Among Subjects with Persistent Viremia Following up to 144 Weeks of Therapy with Tenofovir DF
• Efficacy of Tenofovir DF Treatment in Patients with a Suboptimal Response to Adefovir Dipivoxil
• Risk and Predictors of Mortality or Hepatocellular Carcinoma among Entecavir- or Adefovir-Treated Chronic Hepatitis B Patients with Evidence of Hepatic Decompensation
• Low Rates of Nucleos(t)ide-associated Adverse Events in the Long-term Experience with Entecavir
• MK-5172, the 1st HCV Protease Inibitor with Potent Acyivity Against Resistance Mutations In Vitro
• TMC435 & Drug Interactions: Evaluation of metabolic interactions for TMC435 via cytochrome P450 (CYP) enzymes in healthy volunteers
• EARLY ON-TREATMENT RESPONSES DURING PEGYLATED INTERFERON PLUS RIBAVIRIN ARE INCREASED FOLLOWING 13 DAYS OF COMBINATION NUCLEOSIDE POLYMERASE (RG7128) AND PROTEASE (RG7227) INHIBITOR THERAPY (INFORM-1)
• Combination of TMC435 with two novel NS5B inhibitors increases anti-HCV activity and results in a higher genetic barrier in vitro
• 4 week therapy with the non-nucleosidic polymerase inhibitor BI 207127 in combination with peginterferon alfa2A and ribavirin in treatment naïve and treatment experienced chronic HCV GT1 patients
• Pharmacokinetic-pharmacodynamic (PK-PD) analyses of TMC435 in treatment-naïve hepatitis C (HCV)-infected patients in the OPERA-1 study
• Once-daily NS5A Inhibitor (BMS-790052) Plus Peginterferon-alpha-2a And Ribavirin Produces High Rates Of Extended Rapid Virologic Response In Treatment-naïve HCV-genotype 1 Subjects: Phase 2a Trial - Bristol-Myers Squibb Study AI444014
• SILEN-C2: Early antiviral activity and safety of BI 201335 combined with peginterferon alfa-2a and ribavirin (PegIFN/RBV) in chronic HCV genotype 1 patients with non-response to PegIFN/RBV
• Phase 2 Randomized, Double-Blind Placebo-Controlled Study of Nitazoxanide with Peginterferon Alfa-2a and Ribavirin in Nonresponders with Chronic Hepatitis C Genotype 1: Final Report
• Nitazoxanide + Peg/Rbv in Nonresponders
• Combination of two complementary nucleotide analogues, PSI-7977 and PSI-938, effectively clears wild type and NS5b: S282T HCV replicons - Comparison with combinations of other antiviral compounds
• Sustained Virologic Response following RG7128 1500 mg BID PEG-IFN/RBV for 28 days in HCV Genotype 2/3 prior non-responders
• Vitamin D Supplement improve SVR in Chronic Hepatitis C (Genotype 1) Naïve Patients treated with Peg Interferon and Ribavirin
• Idenix Pharmaceuticals Reports Favorable Pharmacokinetic Data for IDX320, a Potent, Multi-Genotypic Protease Inhibitor for the Treatment of Hepatitis C
• Idenix Pharmaceuticals Reports Positive Results With IDX184 nucleoside polymerase From Interim Analysis of Phase IIa Hepatitis C Study
• Triple Combinations of Direct-Acting Antiviral Agents Demonstrate Robust Anti-HCV Activity In Vitro
• Antiviral Activity, Pharmacokinetics & Safety of IDX184 in Combination with Peg/Rbv in Treatment Naïve Genotype 1
• In Vitro Antiviral Activity of IDX320, a Novel and Potent Macrocyclic HCV Protease Inhibitor
• ANA598 HCV Polymerase Inhititor Safety & Activity + Peg/Rbv in Genotype 1
• 72% OF PATIENTS RECEIVING ANA598 IN PHASE II COMBINATION STUDY WITH INTERFERON AND RIBAVIRIN ACHIEVE UNDETECTABLE LEVELS OF VIRUS AT WEEK EIGHT
• Idenix Pharmaceuticals Reports Favorable Pharmacokinetic Data for IDX320, a Potent, Multi-Genotypic Protease Inhibitor for the Treatment of Hepatitis C
• Discrepancies Between Definitions of Null Response to Treatment with Peginterferon Alfa-2a and Ribavirin: Implications for New HCV Drug Development
• On-Treatment Response-Guided Therapy with Telaprevir q8h or q12h Combined with Peginterferon Alfa-2a or Alfa-2b and Ribavirin in Treatment-Naïve Genotype 1 Hepatitis C (Study C208)
• Activity of Telaprevir Alone or in Combination with Peginterferon Alfa-2a and Ribavirin in Treatment-naïve, Genotype 2 and 3, Hepatitis C Patients: Final Results of Study C209
• On-Treatment Response-Guided Therapy with Telaprevir q8h or q12h Combined with Peginterferon Alfa-2a or Alfa-2b and Ribavirin in Treatment-Naïve Genotype 1 Hepatitis C (Study C208)
• Idenix Pharmaceuticals Reports Positive Results With IDX184 From Interim Analysis of Phase IIa Hepatitis C Study
• Silibinin as Rescue Therapy for Suboptimal Response to Peg/Rbv
• Vitamin D Improves SVR in Naïve Genotype 1 with Peg/Rbv
• InterMune Reports Virologic Response of Ritonavir-Boosted Danoprevir (RG7227/ITMN-191) in Patients with Chronic Hepatitis C
• Identification and Characterization of PPI-461, a Potent and Selective HCV NS5A Inhibitor with Activity Against all HCV Genotypes
• Dose-Ranging, Three-Day Monotherapy Study of the HCV NS3 Protease Inhibitor GS-9256
• Long-term Outcomes Following Combination Treatment with Boceprevir plus PegIntron/Ribavirin (P/R) in Patients with Chronic Hepatitis C, Genotype 1 (CHC-G1)
• Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of Nitazoxanide Plus Peginterferon and Ribavirin in HCV Genotype 1 Naïve Patients: Week 12 Sustained Virologic Response Rate
• GlobeImmune GI-5005 HCV Product Candidate Improves Sustained Virologic Response by 10 Percent, Demonstrating Potential to Be First Therapeutic Vaccine for HCV
• Ritonavir boosting of low-dose danoprevir (RG7227; ITMN-191), HCV NS3/4A protease inhibitor, results in robust reduction in HCV RNA at lower exposures than provided by unboosted regimens
• Telaprevir in Null-Responders & Non-Responders
• VX-222 Vertex NNRTI Polymerase Inhibitor 3 Days Monotherapy
• Merck HCV Protease Inhibitor For Resistance

Lawmakers urge quick passage of bill to boost detection, treatment of hepatitis

By Julian Pecquet - 06/17/10 03:01 PM ET

Lawmakers on the House Oversight panel on Thursday urged Congress to quickly pass legislation to boost the detection and treatment of viral hepatitis, the leading cause of liver cancer in the United States.

The Oversight and Government Reform Committee held the first hearing in several years on the deadly disease, which disproportionately affects blacks and Asians, and pressed for passage of a bipartisan bill that would boost funding by $600 million over the next five years.

The hearing comes on the heels of an Institute of Medicine (IOM) report that highlighted deficiencies with the federal government's response to the epidemic. The report contains two dozen expert recommendations for improvement, including enhanced screening, physician education and the creation of a coordinated system to identify people who have the disease and refer them to care.

About 5.3 million Americans are believed to have hepatitis — the disease causes 12,000 to 15,000 deaths a year — though many don’t know it.

"The current approach [...] is not working," the IOM report says.

The legislation under consideration, introduced in October by Rep. Mike Honda (D-Calif.), has 52 bipartisan co-sponsors. The "Viral Hepatitis and Liver Cancer Control and Prevention Act" is currently in the Energy and Commerce Committee.

The bill would charge the secretary of Health and Human Services with developing and implementing a plan for the prevention, control and medical management of hepatitis B and C; it would also provide federal funding for state-based screening and early intervention programs.

Honda said the bill would eventually save billions of dollars by identifying sick people early. A study by the research firm Milliman found that without federal leadership, the cost of treating hepatitis C alone could more than triple, to $85 billion a year, by 2024.


"We can do a whole lot better than what we're doing," said Oversight panel chairman Edolphus Towns (D-N.Y.). "I think it's a disgrace to have a problem of this nature and to not commit resources."

The panel heard testimony from Honda and Reps. Bill Cassidy (R-La.) and Hank Johnson (D-Ga.). Cassidy is a hepatologist who co-sponsored the bill, and Johnson last year acknowledged he was undergoing treatment for hepatitis C.


Cassidy applauded former President Bill Clinton's children’s vaccination program and said the Honda bill would "similarly save lives." But debate quickly descended into budgetary politics.

Oversight ranking member Darrell Issa (R-Calif.) said Republicans would not vote for any new directed spending unless it's part of the budget bill, which has stalled.

Meanwhile, Democrats bristled at Issa's description of the word "earmark" to describe the bill.


A coalition of more than 175 public and private organizations launched a print ad campaign on Tuesday to coincide with the hearing. The National Viral Hepatitis Roundtable ad is made to look like a movie poster and reads "Mission: Possible."


"If Congress gets on the case now," the ad says, "the leading cause of liver cancer won't stand a chance."


Patient advocates say the Honda bill will help boost funding for hepatitis prevention efforts, which currently only get 2 percent — $19.3 million — of the budget allocated to the Centers for Disease Control and Prevention's National Center for HIV/AIDS, Viral
Hepatitis, STD and TB Prevention. Advocates hope the Honda bill will eventually allow them to get $150 million a year.

Source:
http://thehill.com/blogs/healthwatch/prescription-drug-policy/103923-lawmakers-urge-quick-passage-of-bill-to-boost-detection-treatment-of-hepatitis

Getz Pharma to launch therapy for Hepatitis C patients

* Biotechnology-based drug for hepatitis C will be manufactured by a Pakistani company for the first time


By Irfan Aligi

KARACHI: Getz Pharma would launch the Pegylated Interferon therapy for the treatment of hepatitis C in Pakistan. The new therapy would be highly cost-effective and easy to use as the manufacturer and presenters of the new therapy have considered patients’ care and comfort. It would also be the first time that a biotechnology-based essential drug would be manufactured by Getz Pharma, a Pakistani company. It is pertinent to mention that approximately every 20th person in Pakistan is infected with hepatitis C.

The initiative taken by Getz Pharma to invest in the local manufacturing of Pegylated Interferon (Unipeg) in the country would substantially reduce the cost of treatment for a person suffering from hepatitis C. The company has invested in research and development to formulate this molecule with the help of a team of scientists from the Netherlands, led by Dr Ben Rademaker, a PhD-holder.

Getz Pharma Managing Director and Chief Executive Officer Khalid Mehmood, during a press conference on Thursday, said the size of the country’s pharmacy market is about Rs 119 billion, which is growing by 12 to 13 percent. Henceforth, they have been able to export pharmacy goods to 45 countries around the world. The pharmacy sector in the country is the largest employment provider, with around five million people employed. Pakistan’s pharmacy industry meets 90 percent of the needs of pharmacy goods.

Pharmaceutical exports are at their highest as compared to other corporate sectors in the country and have achieved a 29 percent growth, which is four times of the country’s textile exports. Still, the country’s spending on health according to annual budgetary allocations is just 0.4 percent of the GDP, while Bangladesh is spending 0.8 percent, Khalid said.

Investment: He said Getz Pharma was set up in 1995 as a small company with only 45 employees, while today the number of its employees exceeded 2,500 worldwide, and 1,850 people in Pakistan. Getz Pharma invested Rs 4 billion in revamping existing facilities, in purchasing state-of-the-art production, quality control from 2005 to 2009. It has a plan to meet the 54 percent target of exporting medicines. According to the Federal Bureau of Revenue, Getz Pharma was the second largest taxpayer unit in terms of taxes and duties with an estimated Rs 636 million in 2009, he added.

Khalid said the company’s total investment in Pakistan was Rs 4 billion in the last three years, including investment in manufacturing technology of the first locally manufactured recombinant human insulin. It plans to invest an equal amount in the coming two years in new technologies that would result in local manufacturing of drugs that are currently being imported at high costs. It may be mentioned that Getz Pharma is the single largest exporter of pharmaceutical products from the country. It was estimated that the company’s exports account for approximately 40 percent of the country’s total pharmaceutical exports.

Dr Bernardus Rademaker, speaking on the occasion, said the analytical, toxicological and pharmacokinetic studies for Unipeg (Pegylated Interferon Alpha 2a) had been carried out in Europe, comparing it to the existing research molecule.

New era: He said in addition, bioactivity and potency had also been evaluated at the Centre for Applied Molecular Biology in Lahore, a premier institute of the Science and Technology Ministry. Specialised manufacturing and testing technology is required for manufacturing the Unipeg. He said Getz Pharma had acquired the technology at a substantial investment and a number of these tests were not currently available in the country’s pharmaceutical industry. Through this molecule, Getz Pharma would herald a new biotech era in the country, he added.

To a question, Dr Rademaker said since the molecule was not available in the US, it was not necessary to seek approval form the US FDA. He also said collaboration with Getz Pharma was not business-oriented, but it had been overwhelmingly planned that the hepatitis C affected population of the country should be provided with a cost-effective and latest mode of treatment.

Dr Rademaker holds a PhD in biotechnology from the State University Utrecht, Holland. He is the founder and CEO of InProPharma, a company specialising in technology platforms for the production of biologically active proteins. Prior to setting up his own company, Rephartox BV, a contract research company for the pharmaceutical industry, he was the director of Corporate Drug Development at the Rhein Biotech NV, Maastricht and the Green Cross Vaccine Company, Seoul, Korea. He is a member of the Dutch Pharmacological Society and is a registered pharmacologist. He has authored more than 50 scientific publications, and many regulatory affairs documents.

http://www.dailytimes.com.pk/default.asp?page=2010%5C06%5C18%5Cstory_18-6-2010_pg7_17

Benitec Limited (ASX:BLT) Granted Hepatitis C RNA Interference Patent In US

Melbourne, June 18, 2010 (ABN Newswire) - Benitec Limited (ASX:BLT) (PINK:BNIKF) are pleased to announce that US Patent 7727970 "Multiple promoter expression cassettes for simultaneous delivery of RNAi agents targeted to Hepatitis C virus" has been granted by the United States Patent and Trademark Office (USPTO). The granted claims cover the use of an RNA interference construct (with multiple promoters) to inhibit the level of Hepatitis C virus in animal cells, tissues and organs. Moreover, the USPTO has granted Benitec an additional 805 days patent term in recognition of the delays in examining the patent application. Additional related applications remain pending to extend the scope of protection.


Benitec has licensed the rights to use this patent for Hepatitis C exclusively to Tacere Therapeutics, Inc., who recently announced that Pfizer has exercised its option to further develop and commercialise Tacere's Hepatitis C Virus (HCV) compounds.

Benitec's Chief Scientific Officer, Dr Peter French said, "The grant of this patent is an important further recognition of our dominant global position in the transformational DNA-directed RNA interference field and provides increased depth and breadth to our patent portfolio. Benitec's ddRNAi-related patent estate (solely owned or licensed exclusively for humans from CSIRO) currently comprises over 100 patents and patent applications covering 20 jurisdictions, of which more than 30 are granted, accepted or allowed."

Link: http://www.abnnewswire.net/media/en/docs/63116-ASX-BLT-596073.pdf


About Benitec Limited

Benitec Limited (ASX:BLT) (PINK:BNIKF) is an Australian biotechnology company focused on licensing its extensive intellectual property portfolio and developing therapeutics to treat serious diseases using its proprietary ddRNAi technology. For additional information, please visit http://www.benitec.com/ .


Contact

Mel Bridges
Executive Director
Mob: +61-413-051-600
Email: mbridges@benitec.com

Peter French
Chief Executive Officer
Mob: +61-412-457-595
Email: pfrench@benitec.com

http://www.abnnewswire.net/press/en/63116/Benitec_Limited_(ASX:BLT)_Granted_Hepatitis_C_RNA_Interference_Patent_In_US.html

We will not be silent on viral hepatitis

By Rep. Mike Honda (D-Calif.) - 06/18/10 09:05 AM ET

At a Government and Oversight Reform Committee hearing this week, I testified to the devastating and deadly impacts of an unsuspecting disease: Viral Hepatitis. The fact that I was joined by Dr. Howard Koh, Assistant Secretary for Health, and Dr. John Ward, Director of the Viral Hepatitis Program at the Center for Disease Control, underscores the importance of the issue. Government oversight is a good start to getting the American public more informed, but much more is needed, according to the Institute of Medicine's 2010 report titled "Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C".

Few realize how highly infectious viral hepatitis is. Hepatitis B is 100 times more infectious than HIV. Few realize that, left untreated, it can cause liver disease, liver cancer, and premature death decades after infection. Few realize that roughly 2 billion people worldwide have been infected with Hepatitis B; over 170 million people are chronically infected with Hepatitis C; and in this nation alone, an estimated 5.3 million people are infected with either Hepatitis B or Hepatitis C. Tragically, an average of two-thirds of those infected are unaware of their status.

It is no surprise, then, that some are calling this a silent crisis. However, we cannot afford to be silent anymore. In fact, we will not be silent any more. Why? Because our countrymen and women are dying daily, needlessly, from a disease that is entirely preventable if detected early. Each year, approximately 15,000 people die from liver cancer or liver diseases related to Hepatitis B and Hepatitis C. That's over 40 Americans dying every day, with no state or district in our nation exempt from its deadly reach.

Beyond the tragic and preventable loss of human life and its subsequent hit to our country's productivity, the costs to our country our explicitly economic as well. Without effective prevention and vaccination methods in place, chronic Hepatitis B and C is expected to cost our country at least $20 billion, in treatments alone, over the next 10 years. As a result, over the same time frame, commercial and Medicare costs will more than double. Projecting further out, over the next 20 years, total medical costs for patients with Hepatitis C infection are expected to increase more than 2.5 times from $30 billion to over $85 billion.

We must, therefore, change the way Hepatitis is diagnosed and treated. With the help of Chairman Towns and Reps Cassidy, Johnson, and Dent, I introduced the Viral Hepatitis and Liver Cancer Control and Prevention Act, H.R. 3974, which provides nearly $600 million over the next five years to treat hepatitis. Our legislation focuses federal efforts on a strategy that saves lives and makes our health system more efficient. We bring together the common concerns of the diverse viral hepatitis community to fight chronic viral hepatitis by establishing, promoting, and supporting a comprehensive prevention, research and medical management referral program. And we strengthen the ability of the Center for Disease Control to support state health departments in the prevention, immunization and surveillance efforts.

Through this legislation, and with strategic investments in public health and prevention program, billions of dollars can be saved, so too the lives of tens of thousands of people in states and cities all over American. I urge all of you to join me in supporting activities that promote early detection and education. With your help, we can sound the alarm on this silent crisis.

Source:
http://thehill.com/blogs/congress-blog/healthcare/104081-we-will-not-be-silent-on-viral-hepatitis-rep-mike-honda

NVHR Launches Targeted Print Advertising Campaign Urging Swift Congressional Action on Secret Epidem

As Congress prepares to shine a spotlight this week on chronic viral hepatitis, the National Viral Hepatitis Roundtable (NVHR) today launched a new targeted print advertising campaign to urge swift action on bipartisan legislation providing federal funding for state-based screening and early intervention programs. NVHR's new advertising initiative comes in advance of a hearing Thursday, June 17, before the full House Oversight & Government Reform Committee, chaired by Chairman Ed Towns (D-NY) and Ranking Member Darrell Issa (R-Calif.). The Committee has invited testimony from a diverse panel of witnesses who will offer strategies for implementing expert recommendations made earlier this year by the Institute of Medicine (IOM).

NVHR is a coalition of more than 175 public, private, and voluntary organizations dedicated to reducing the incidence of infection, morbidity, and mortality from chronic viral hepatitis that afflicts more than 5 million Americans. http://www.nvhr.org/

"NVHR's new advertising initiative is a timely reminder to Congress, the Administration, and all stakeholders that federal action is desperately needed this year to help combat this insidious disease that affects over 5 million Americans and their loved ones," said Ms. Lorren Sandt, Chair of the National Viral Hepatitis Roundtable (NVHR) and Executive Director of Caring Ambassadors Program, based in Portland, OR. "Six months ago, the Institute of Medicine issued nearly two-dozen expert recommendations for improving the federal government's response to the viral hepatitis epidemic. The pressing challenge now before Congress and the Administration is to provide federal funding to translate the IOM report into swift and decisive action."

Under the banner of "Mission: Possible," NVHR's new advertisement highlights the IOM report and urges action on HR 3974. The advertisement also features the tagline "If Congress gets on the case now, the leading cause of liver cancer won't stand a chance."

Thursday's hearing before the House Oversight & Government Reform Committee is an important step forward in this fight. An estimated 5.3 million Americans have been infected with chronic viral hepatitis B or C - and with most unaware of their infection, millions are at risk of developing life-threatening complications, especially African Americans and Asian Americans. Without detection and treatment, chronic viral hepatitis leads to liver cancer, cirrhosis, or liver failure. In the absence of federal leadership, the research firm Milliman estimates that public and private payers' cost of treating chronic viral hepatitis C alone will more than triple by 2024 to $85 billion annually. Medicare and Medicaid would absorb a disproportionate share of these added costs.

HR 3974, "The Viral Hepatitis and Liver Cancer Control and Prevention Act," is sponsored by Representatives Mike Honda (D-Calif.), Charles Dent (R-Pa.) and 49 other House Members and would help turn the tide. The Honda-Dent legislation would increase the ability of the CDC to support state health departments in their prevention, immunization and surveillance, and referral to care efforts. Much of the Honda-Dent legislation tracks with the IOM's recommendations.

Source: National Viral Hepatitis Roundtable

Source

A nutritional supplement for treating chronic hepatitis C: Viusid

Contact: Ye-Ru Wang

wjg@wjgnet.com
86-105-908-0039
World Journal of Gastroenterology
 
The pathogenesis of chronic hepatitis C (CHC) is associated with severe oxidative stress and non-selective immunological disturbance that lead to necroinflammation and the progression of fibrosis. Several trials have suggested that antioxidant and immunostimulant therapies may have a beneficial effect. Two previous clinical studies have reported that the Viusid related effect on histologic features, especially fibrosis, appears to be associated with antioxidant and/or immunomodulatory properties. However, the putative mechanism of action of Viusid is unknown.


A research article to be published on June 7, 2010 in the World Journal of Gastroenterology addresses this question. The authors reported the results of a randomized double-blind and placebo-controlled study to evaluate the effect of Viusid on oxidative stress and cytokine parameters in patients with CHC who had been nonresponders to previous antiviral therapy with peginterferon plus ribavirin and infected with genotype 1.

Their results show that Viusid improves oxidative stress through reduction of lipid peroxidation products and has an immunomodulatory effect on cytokine secretion via increased production of IFN-γ and IL-10, decreased production of IL-1α, and stabilized TNF-α secretion in patients with CHC who have failed previous antiviral treatment. Thus, Viusid is an interesting strategy of treatment for those patients who don't eradicate their viral infection or when antiviral treatment is contraindicated (decompensated cirrhosis). The administration of Viusid was well tolerated. Further studies are needed to evaluate the clinical impact of the administration of Viusid in patients with end-stage liver disease secondary to CHC.

###

Reference: Gomez EV, Perez YM, Sanchez HV, Forment GR, Soler EA, Bertot LC, Garcia AY, del Rosario Abreu Vazquez M, Fabian LG. Antioxidant and immunomodulatory effects of Viusid in patients with chronic hepatitis C. World J Gastroenterol 2010; 16(21): 2638-2647 http://www.wjgnet.com/1007-9327/full/v16/i21/2638.htm

Correspondence to: Dr. Eduardo Vilar Gomez, PhD, Associated Professor, Department of Hepatology, National Institute of Gastroenterology, 25th Avenue, 503, Vedado, Havana 10400, Cuba. vilar@infomed.sld.cu

Telephone: +53-7-8325067 Fax: +53-7-8333253

About World Journal of Gastroenterology

World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2008 IF: 2.081. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.

http://www.eurekalert.org/pub_releases/2010-06/wjog-ans061710.php

One Year After the Launch of Telaprevir and Boceprevir, Surveyed Physicians Expect to Prescribe Triple Therapy Regimens to 90 Percent of Their Hepatitis C Virus Patients

press release
June 17, 2010, 9:00 a.m. EDT

Twenty-Five Percent of Surveyed MCOs Expect to Add Both Telaprevir and Boceprevir to Their Formularies, According to a New Report from Decision Resources

WALTHAM, Mass., June 17, 2010 /PRNewswire via COMTEX/ -- Decision Resources, one of the world's leading research and advisory firms for pharmaceutical and healthcare issues, finds that, based on clinical profiles provided to them, surveyed clinicians estimate that one year after the launch of Vertex Pharmaceuticals/Johnson & Johnson/Mitsubishi Tanabe Pharma's telaprevir and Merck's boceprevir, at least 90 percent of hepatitis C virus (HCV) patients will be treated with triple therapy regimens.


The new Physician & Payer Forum report entitled Hepatitis C: Reimbursement and Uptake of Novel Antivirals Among Payers and Prescribers finds that surveyed physicians expect to treat 71 percent of treatment-naive and 78 percent of nonresponder patients with telaprevir/peg-IFN/ribavirin and 19 percent of treatment-naive and nonresponders with boceprevir/peg-IFN/ribavirin. Similar to clinicians, managed care organizations' (MCO) pharmacy directors are open to reimbursing telaprevir and boceprevir. However, surveyed pharmacy directors do not indicate a clear preference for either one of these protease inhibitors.

"Only 10 percent of the pharmacy directors we surveyed do not expect to add telaprevir or boceprevir to their drug formularies," said Decision Resources Analyst Alexandra Makarova, M.D. Ph.D. "The remaining surveyed pharmacy directors are split regarding the choice of the protease inhibitor for addition to their formularies. Twenty-five percent expect to add both telaprevir and boceprevir, while 15 percent will add only telaprevir and 5 percent will add only boceprevir. Forty percent of pharmacy directors will make their choice based on the relative cost of each agent."

The report also finds that almost half of surveyed clinicians indicate that they will use Roche's Pegasys and Merck's PegIntron interchangeably in combination with an HCV-specific antiviral agent even if this agent was evaluated in clinical trials involving only one of these peg-IFNs. However, one-third of doctors expect to combine a novel HCV-specific antiviral agent only with the peg-IFN that was used with the antiviral agent in clinical trials. These physicians indicate that they will likely use Pegasys in triple therapy regimens as the majority of HCV-specific antiviral agents are being evaluated with Pegasys rather than PegIntron.

Hepatitis C: Reimbursement and Uptake of Novel Antivirals Among Payers and Prescribers is based on a U.S. survey of 74 gastroenterologists, 26 hepatologists and 20 MCO pharmacy directors. Their responses were compared to assess similarities and differences of opinion regarding clinical, economic and scientific factors.

About Decision Resources

Decision Resources (www.decisionresources.com ) is a world leader in market research publications, advisory services and consulting designed to help clients shape strategy, allocate resources and master their chosen markets. Decision Resources is a Decision Resources, Inc. company.

About Decision Resources, Inc.

Decision Resources, Inc. is a cohesive portfolio of companies that offers best-in-class, high-value information and insights on important sectors of the healthcare industry. Clients rely on this analysis and data to make informed decisions. Please visit Decision Resources, Inc. at www.DecisionResourcesInc.com .

All company, brand, or product names contained in this document may be trademarks or
registered trademarks of their respective holders.

http://www.marketwatch.com/story/one-year-after-the-launch-of-telaprevir-and-boceprevir-surveyed-physicians-expect-to-prescribe-triple-therapy-regimens-to-90-percent-of-their-hepatitis-c-virus-patients-2010-06-17?reflink=MW_news_stmp

Congress to Hold Hepatitis Hearing this Thursday

Action Alert

(posted June 16, 2010)

Hepatitis C Advocates UNITED! Action Alert

Congress to Hold Hepatitis Hearing this Thursday

Urge Your Representative to Lead the Fight Against the “Secret Epidemic”

Background

On Thursday, June 17, the House Committee on Oversight and Government Reform will hold a hearing entitled “Viral Hepatitis: The Secret Epidemic.” This hearing, under the leadership of Chairman Edolphus Towns, will examine issues surrounding the prevention, detection, management and control of viral hepatitis.

This hearing provides an excellent opportunity to educate Members of Congress about the hepatitis B and C epidemics and the recommendations made earlier this year on how the federal government must improve its response in the Institute of Medicine (IOM) report, Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C. The hearing also follows a major World Hepatitis Day rally at the U.S. Capitol nearly a month ago. There is growing momentum to demand that Congress fully fund hepatitis programs and take leadership on an issue that impacts millions of Americans.

Please take a few minutes to urge your House Representative to learn about the issues raised in this hearing and to fight for more viral hepatitis leadership!

Action

It is urgent that your calls be made immediately. Please call your Representative’s Washington, DC office. Ask to speak to the staff person who handles health issues. You can call your Representative at 202.225.3121. You will get the Capitol switchboard. Ask to be connected to your Representative’s office. If you don’t know who your Representative is, you can go online to http://www.house.gov/ to determine your Member of Congress. Whether you speak to this person directly or leave a message, tell them:

“My name is ___________ and I am a constituent of Representative ___________. I am calling to let you know about an important hearing this week on Thursday, June 17 at 10:00 AM held by the House Committee on Oversight and Government Reform entitled “Viral Hepatitis: The Secret Epidemic.” This hearing will focus on the federal government’s response to viral hepatitis; an epidemic that affects over 5 million Americans, most of whom do not know they are infected because they have no symptoms. Viral hepatitis such as hepatitis B and C are the leading causes of liver cancer and cause 15,000 premature deaths each year.

I urge Representative ___________ to support this hearing and to do everything he/she can to fight this silent epidemic, including fighting for increased funding for viral hepatitis programs at the Centers for Disease Control and Prevention, supporting in any way possible new health reform monies to hepatitis services and co-sponsoring the Viral Hepatitis and Liver Cancer Control and Prevention Act (H.R. 3974). This is important to me because _________________.”

It is especially important to encourage your Representative attend the hearing if he or she is on the House Committee on Oversight and Government Reform (see membership list below). Urge him/her to attend this important hearing to show leadership!

Committee Members:

Democrats:
Chairman Edolphus Towns (NY)

Paul Kanjorski (PA)

Carolyn Maloney (NY)

Elijah Cummings (MD)

Dennis Kucinich (OH)

John Tierney (MA)

William Lacy Clay (MO)

Diane Watson (CA)

Stephen Lynch (MA)

Jim Cooper (TN)

Gerald Connolly (VA)

Mike Quigley (IL)

Marcy Kaptur (OH)

Eleanor Holmes Norton (DC)

Patrick Kennedy (RI)

Danny Davis (IL)

Chris Van Hollen (MD)

Henry Cuellar (TX)

Paul Hodes (NH)

Christopher Murphy (CT)

Peter Welch (VT)

Bill Foster (IL)

Jackie Speier (CA)

Steve Driehaus (OH)

Judy Chu (CA)



Republicans:

Ranking Member Darrell Issa (CA)

Dan Burton (IN)

John Mica (FL)

John Duncan, Jr. (TN)

Michael Turner (OH)

Lynn Westmoreland (GA)

Patrick McHenry (NC)

Brian Bilbray (CA)

Jim Jordan (OH)

Jeff Flake (AZ)

Jeff Fortenberry (NE)

Jason Chaffetz (UT)

Aaron Schock (IL)

Blaine Luetkemeyer (MO)

Anh “Joseph” Cao (LA)


Hepatitis C Advocates UNITED! is a national, grassroots network of individuals and organizations fighting for increased funding for hepatitis programs and legislation to mount a comprehensive federal effort to fight the disease. We design grassroots strategies to educate our elected representatives about the need for adequate HCV funding and policies, including action alerts, sign-on letters legislative meetings, media activities, and other campaigns. We also share information and strategies on state-level issues and campaigns. Hepatitis C Advocates UNITED! was formed by the Hepatitis Appropriations Partnership (HAP) and the National Hepatitis C Advocacy Council (NHCAC), and the National Viral Hepatitis Roundtable (NVHR). To join the network, send an email to rclary@projectinform.org with “subscribe” in the subject field. Please include your name and city/state in the email.

Source