Showing posts with label A-EASL 2012. Show all posts
Showing posts with label A-EASL 2012. Show all posts

Sunday, August 19, 2012

2012 EASL-Three Hepatology experts comment on hepatitis C abstracts

In the August issue of Gastroenterology & Endoscopy the following hepatology experts: Nezam Afdhal, MD, Stuart C. Gordon, MD and Ira Jacobson, MD comment on their favorite abstracts from this year's liver meeting.
 
Experts' Picks: Best of the EASL/International Liver Congress 2012
 
Hepatology in Focus

Compiled and written by David Wild

Gastroenterology & Endoscopy News asked several hepatology experts to select their favorite abstracts from this year’s European Association for the Study of the Liver/International Liver Congress, held in Barcelona.

Abstracts:

Safety of Telaprevir or Boceprevir in Combination with Peginterferon alfa/Ribavirin in Cirrhotic non-Responders: First Results of the French Early Access Program (ANRS C020-CUPIC) (Hezode C et al)

Ribavirin Dose Modification in Treatment-Naive and Previously Treated Patients who Received Telaprevir Combination Treatment: No Impact on Sustained Virologic Response in Phase 3 Studies (Sulkowski MS et al)

A Randomized Trial Comparing Ribavirin Dose Reduction Versus Erythropoietin for Anemia Management in Previously Untreated Patients with Chronic Hepatitis C Receiving Boceprevir Plus Peginterferon/RIBA (Poordad FF et al)

Efficacy and Safety of Anticoagulation in Patients with Cirrhosis and Portal Vein Thrombosis (Seijo S et al)

Impact of HCV Treatment and Disease Severity on Health Care Costs in Chronic HCV Patients: Analysis of a Large U.S. Private Health Insurance Claims Database (Gordon SC et al)

ATOMIC: 97% RVR for PSI-7977 + PEG/RBV x 12 Week Regimen in HCV GT1: An End to Response-Guided Therapy? (Kowdley et al)

ELECTRON: Once Daily PSI-7977 Plus RBV in HCV GT1/2/3 (Gane EJ et al)

12-Week Interferon-Free Regimen of ABT-450/R + ABT-333 + Ribavirin Achieved SVR12 in More Than 90% of Treatment-Naive HCV Genotype-1-Infected Subjects and 47% of Previous Non-Responders (Poordad F et al

Potent Viral Suppression with All-Oral Combination of Daclatasvir (NS5A Inhibitor) and GS-7977 (NS5B Inhibitor), +/- Ribavirin, in Treatment-Naïve Patients with Chronic HCV GT1, 2, or 3 (Sulkowski M et al

Click here to view comments and abstracts

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Saturday, May 26, 2012

May 26 Weekend Reading-Relevant Hepatitis C Research and News

Girl Reading  by Pablo Picasso

Greetings,
Most weekends this blog offers up a few substantial links to relevant HCV information, click here for previous "Weekend Reading" articles. Hepatitis C New Drug Research And Liver Health has an article database which includes full-text and abstracts on hepatitis C.  View the RSS feed for this weekend of updates.

Meeting Coverage In The News

EASL 2012

EASL: Telaprevir 100% Effective for IL28B CC, Adding VX-222 Overcomes Unfavorable Genes
23 May 2012

Written by Liz Highleyman

Adding telaprevir (Incivek) to pegylated interferon and ribavirin cured all hepatitis C patients with the favorable IL28B gene pattern, researchers reported at the 47th International Liver Congress (EASL 2012) last month in Barcelona. Another study found that adding the experimental HCV protease inhibitor VX-222 raised cure rates even for those with unfavorable IL28B patterns.
DDW, the annual meeting of the American Gastroenterological Association (AGA) Institute, is jointly sponsored by the American Association for the Study of Liver Diseases, the AGA, the American Society for Gastrointestinal Endoscopy and the Society for Surgery of the Alimentary Tract.

Increased mortality observed in patients with HCV and diabetes
May 23, 2012

Those with both hepatitis C and diabetes had a higher mortality rate when compared with those who had either condition alone, according to research presented during Digestive Disease Week 2012.
When we observed the rates for patients who had both hepatitis C and diabetes, we saw that the mortality rate was significantly increased — at least three times the amount of patients died in the group with both hepatitis C and diabetes compared with patients who had neither condition,”

Meira Abramowitz, MD, of the division of internal medicine at SUNY Downstate Medical Center in Brooklyn, N.Y., told Infectious Disease News.

Abramowitz and colleagues conducted a retrospective chart review of patients treated at the VA New York Harbor Healthcare System from 2002 to 2003. Mortality data were collected from 2011.
Patients with HCV were identified from a registry of more than 6,000 patients with HCV. These patients were age-matched with other patients without HCV from the VA system, some of whom had diabetes.

The final cohort included 1,846 patients, of whom 18.8% had neither HCV nor diabetes and 12.8% had both. Of the 579 patients with diabetes, 31.3% died vs. 20.6% of the 1,213 patients without diabetes. Of the 1,141 patients with HCV, 24.5% died vs. 24.1% of the 692 patients without HCV.

Of the 237 patients with both HCV and diabetes, 36.3% died vs. 20.8% of the 867 patients with HCV alone, 27.8% of the 342 patients with diabetes alone and 20.2% of the 346 patients with neither disease. The OR for mortality in patients with diabetes vs. patients without diabetes was 1.7 (95% CI, 1.3-2.24). This increased to 1.89 when the researchers compared patients with both HCV and diabetes to patients with neither disease (95% CI, 1.45-2.46).

“We are not entirely sure why this mortality increase took place because both of these conditions have their own individual complications,” Abramowitz said. “Hepatitis C can develop into hepatocellular carcinoma and hepatic encephalopathy, while diabetes can progress into diabetic nephropathy and diabetic neuropathy with accompanying cardiovascular complications.”
References:
  • Abramowitz M. #MO1905. Presented at: Digestive Disease Week 2012 Annual Meeting; May 19-22; San Diego.
Disclosures:
  • Dr. Abramowitz reports no relevant financial disclosures.

DDW

View Additional DDW articles..............

Research

ISSUE: MAY 2012 | VOLUME: 63:5

Update on the Diagnosis and Treatment of Hepatitis C

by Arun B. Jesudian, MD and Ira M. Jacobson, MD

Hepatitis C virus (HCV) infection is a national and global public health concern, affecting up to 4 million individuals in the United States and 200 million individuals worldwide. Despite a declining incidence of new HCV infections in the United States, the prevalence of advanced liver disease secondary to chronic HCV infection, including cirrhosis and hepatocellular carcinoma, is expected to rise in the coming years.

Download to read this article in PDF document:
Update on the Diagnosis and Treatment of Hepatitis C

This article is in PDF format and it requires Abobe Reader. If you do not have Adobe Reader installed on your computer then please download and install from the link below.
Download Adobe Reader

Newsletters/Bulletins

NICE Bites is a monthly bulletin which summarises key prescribing points from NICE guidance. This edition includes two topics; Anaphylaxis and Hepatis C – technology appraisals.

Healthy You

Oregon State University

Like curry? New biological role identified for compound used in ancient medicine

CORVALLIS, Ore. – Scientists have just identified a new reason why some curry dishes, made with spices humans have used for thousands of years, might be good for you.

New research at Oregon State University has discovered that curcumin, a compound found in the cooking spice turmeric, can cause a modest but measurable increase in levels of a protein that's known to be important in the "innate" immune system, helping to prevent infection in humans and other animals.

This cathelicidin antimicrobial peptide, or CAMP, is part of what helps our immune system fight off various bacteria, viruses or fungi even though they hadn't been encountered before.
Prior to this, it was known that CAMP levels were increased by vitamin D. Discovery of an alternative mechanism to influence or raise CAMP levels is of scientific interest and could open new research avenues in nutrition and pharmacology, scientists said.

Turmeric is a flavorful, orange-yellow spice and an important ingredient in many curries, commonly found in Indian, South Asian and Middle Eastern cuisine. It has also been used for 2,500 years as a medicinal compound in the Ayurvedic system of medicine in India – not to mention being part of some religious and wedding ceremonies. In India, turmeric is treated with reverence.

The newest findings were made by researchers in the Linus Pauling Institute at OSU and published today in the Journal of Nutritional Biochemistry, in collaboration with scientists from the University of Copenhagen in Denmark. The work was supported by the National Institutes of Health.

"This research points to a new avenue for regulating CAMP gene expression," said Adrian Gombart, an associate professor of biochemistry and biophysics in the Linus Pauling Institute. "It's interesting and somewhat surprising that curcumin can do that, and could provide another tool to develop medical therapies."

The impact of curcumin in this role is not nearly as potent as that of vitamin D, Gombart said, but could nonetheless have physiologic value. Curcumin has also been studied for its anti-inflammatory and antioxidant properties.

"Curcumin, as part of turmeric, is generally consumed in the diet at fairly low levels," Gombart said. "However, it's possible that sustained consumption over time may be healthy and help protect against infection, especially in the stomach and intestinal tract."

In this study, Chunxiao Guo, a graduate student, and Gombart looked at the potential of both curcumin and omega-3 fatty acids to increase expression of the CAMP gene. They found no particular value with the omega-3 fatty acids for this purpose, but curcumin did have a clear effect. It caused levels of CAMP to almost triple.

There has been intense scientific interest in the vitamin D receptor in recent years because of potential therapeutic benefits in treating infection, cancer, psoriasis and other diseases, the researchers noted in their report. An alternative way to elicit a related biological response could be significant and merits additional research, they said.

The CAMP peptide is the only known antimicrobial peptide of its type in humans, researchers said. It appears to have the ability to kill a broad range of bacteria, including those that cause tuberculosis and protect against the development of sepsis.



Is coffee good for the liver?
ISIC the Institute for Scientific Information on Coffee©
14th May 2012

Questions patients ask

Q: Is coffee good for the liver?
A: Research suggests that regular, moderate coffee consumption can lower people’s risk of developing a range of liver diseases – including cancer, fibrosis (scar tissue that builds up within the liver) and cirrhosis (the result of a long-term build up of scar tissue within the liver).

Q: How many cups of coffee do I need to drink to see a benefit?
A: It is too early to make specific recommendations concerning the levels of coffee intake that may be beneficial for liver function. Research suggests that regular, moderate coffee consumption may be beneficial

1,2. However certain patients with specific conditions may need to limit their caffeine consumption. For example, pregnant women are advised to limit their caffeine intake to 200-300mg per day – the equivalent amount found in 2-3 regular cups of coffee.

Q: Are the benefits of coffee down to caffeine?
A: While research has suggested that caffeine may slow down the progression of liver fibrosis, alcoholic cirrhosis and liver cancer

3,4,5, the extent to which caffeine is implicated in the reduced risk of developing these diseases remains unclear. Research also suggests that other coffee constituents, including cafestol and kahweol6 (naturally occurring compounds found in the oily part of coffee), and antioxidants may have a beneficial effect on liver function.

Q: Is decaffeinated coffee as good as regular coffee?
A: Research suggests that caffeine might play a role in the relationship between coffee drinking and lower risk of liver disease; however, currently there are no published studies specifically investigating the effects of decaffeinated coffee on liver function.

Q: If I’m a coffee drinker, can I drink more alcohol without increasing my risk of liver disease?
A: No. All medical advice makes clear that excessive alcohol consumption is detrimental to health. Adults, who choose to consume alcohol, should be aware of the recommended advice for safe consumption. While scientific research suggests that coffee drinking may have a beneficial effect on liver function, the risks associated with excessive alcohol consumption are not counter balanced by coffee consumption.

Q: I’ve heard that the effects of alcohol on the liver can be different for women than for men. Is the same true for coffee?
A: Generally, the effect of coffee drinking does not differ between the sexes; however, some groups, such as pregnant women, smokers, or women taking hormone replacement therapy do metabolise caffeine at a different rate to those in the general population. Pregnant women are advised to limit their caffeine intake to 200-300mg per day – the equivalent amount found in 2-3 regular cups of coffee.

Q: Do all types of coffee have the same effect?
A: Studies investigating the relationship between coffee and liver function have demonstrated beneficial effects in various types of coffee preparation, including filtered, instant and espresso coffee.

Q: Is it safe for individuals with liver disease to drink coffee?
A: Yes, there is no evidence to suggest that moderate coffee drinking poses any dangers for individuals with liver disease. In fact, some studies suggest coffee may slow down the progression of liver disease in some patients.

Q: Does coffee have any benefits for individuals with liver disease?
A: Research has shown that individuals with liver disease who regularly drink moderate amounts of coffee tend to display a milder progression of the disease7,8.
 Source and References

May 24
Think you eat a nutritious diet but still find yourself battling sugar cravings, feeling fatigued and struggling to lose weight? Then carve out time today to watch this talk by Stanford internist Nicole Peoples, DO. In this video lecture, she explains what happens once food enters your system, how your body responds to it and why the food choices you’re making could be contributing to these and other symptoms.






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Sunday, May 13, 2012

EASL Video Highlights-BMS-790052/BMS-650032 Also PSI-7977 PROTON and ELECTRON

Happy Mothers Day!

A special heartfelt Mothers day goes out to all the ladies who are burdened with the challenge of living with HCV.  Taking care of a family requires exuberant energy which at times can be difficult when living with this disease. The fatigue is unbearable and the constant worry that this disease will hinder the ability to raise our children is enormous.

May this Mothers day be filled with special moments, and lasting memories.

~Tina~

EASL video presentations

Today, I am once again pointing readers back to "ViralEd " and their coverage of the 2012 EASL meeting which took place last month in Barcelona (Spain). The site is great source for easy to understand information, although like any site offering continuing medical education (CME), it requires a free quick registration.

For anyone newly diagnosed with HCV understanding key data on the many HCV drugs in development is nothing less then overwhelming.

For me, the coverage of the March EASL at ViralEd is, well, enjoyable. Maybe not as enjoyable as breakfast in bed on Mothers day; that is if you get breakfast in bed. I'm still waiting to hear those three little words; Happy Mothers day. These days my kids communicate online through the social network or by text messaging. So I wait,  hoping to get tagged in a photo on Facebook, or maybe a text asking grandma to babysit. Anyhow, the entertaining video discussion format at ViralEd is less clinical, and easily digested.

Below on the blog are just a few EASL video abstracts from ViralEds "Expert Poster Review and Discussion" presentation.

Please consider viewing the complete program -"The 47th Annual EASL: Advances in Chronic Hepatitis C Management and Treatment" Unless the kids call and ask you out to lunch; I'm still waiting for my call. Not to worry its early in the day, I'd call them but for some reason they screen their calls.

Another video on the blog today was published on May 7 by , the EASL video talks a little about last months meeting, with a mention of interferon free therapy and the field of hepatology.

I wonder if I should send my eldest a text message ? I'll wait, one of my three kids will call.

*The data presented at the EASL should be considered preliminary until it has been reviewed and published in a peer-reviewed publication.

EASL 2012 Poster Program Abstract 14

Dual Oral Therapy with the NS5A Inhibitor (BMS-790052) and NS3 PI (BMS-650032) in HCV Genotype 1B-infected Null Responder or Ineligible/Intolerant to Peginterferon/Ribavirin



I watched both videos, and still no Happy Mothers Day text or any photo action on Facebook.

Poster/Presentation Listing @ ViralEd








Published on May 7, 2012 by

THE INTERNATIONAL LIVER CONGRESS 2012 - TALKING HEADS

A video of prominent EASL members who generously dedicated precious time to the EASL film crew onsite in Barcelona to talk about key elements of the congress and the ever moving field of hepatology.





Shut the front door ! I just received a call from one-of my- three children, so off I go to enjoy Mothers day. So happy I sent that text!

Happy MOM !



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Tuesday, May 8, 2012

New Drugs Require New Terms for HCV Virologic Response

New Drugs Require New Terms for HCV Virologic Response
Daniel M. Keller, PhD
Source - Medscape

May 8, 2012 (Barcelona, Spain) — The development of drugs to treat hepatitis C virus (HCV) is progressing rapidly, but the terminology to quantify virologic response is lagging. A consortium of interested organizations is creating nomenclature for virologic responses in trials of direct-acting antiviral drugs, which are small-molecule inhibitors of viral enzymes that hold the promise of interferon-free treatment regimens.

During a poster session here at the International Liver Congress 2012, Donald Jensen, MD, professor of medicine at the University of Chicago Medical Center in Illinois, presented the rationale for and principles of the nomenclature being developed by the Hepatitis C Virus Drug Development Advisory Group (HCV DrAG).

HCV DrAG is a project of the Forum for Collaborative HIV Research, which has a subgroup devoted to HCV research with experts from the American Association for the Study of Liver Diseases, the European Association for the Study of the Liver (EASL), and the Infectious Diseases Society of America. The forum is a broad consensus panel that includes industry representatives, members of American and European drug regulatory agencies, academic investigators, and representatives of advocacy groups.

Direct-acting antiviral drugs have potent antiviral actions and appear to produce a more rapid virologic response, with or without interferon, than interferon-based regimens without the new drugs. More intuitive and flexible virologic measures are needed that can adapt to these advances in HCV treatment.
"We wanted to do this before all the new oral therapies hit the market," Dr. Jensen told Medscape Medical News.

He said current terminology can be confusing when describing virologic response to the new therapies. "We felt that there was a need to have this description of virologic responses more consistent across studies — something that could also be used in manuscripts and in clinical practice," he said. A panel of experts set out to develop a nomenclature "that was intuitive, that made sense, and that was descriptive of virologic responses during the course of therapy for hepatitis C."

Considerations for Nomenclature Development
Comparisons between drugs or regimens is difficult or impossible without a common nomenclature. The propsed nomenclature will assign a description of the time frame and the level of response to the measures, as opposed to a qualitative description such as "rapid virologic response."
The proposed terminology for key decision points in treatment trials takes into account the assay-specific lower limits of quantification of HCV RNA (as opposed to lower limits of detection), with responses defined as quantifiable or unquantifiable levels of HCV RNA.

Key components in expressing virologic response are the week of treatment, the quantifiable decline in viral load from initiation of treatment (expressed as log10 decline), any lead-in treatment duration (days or weeks), and whether the target HCV RNA was detected or not. The panel explains that the lower limit of quantitation (LLOQ) of a virologic assay should be clearly specified. (One common problem in current trials is the use of different commercial assay systems.) The target may or may not be detected at levels below the LLOQ.

HCV viremia at levels less than the LLOQ in trials without a lead-in treatment period — what has been called a rapid virologic response — would now be W4U, meaning an unquantifiable HCV RNA level at week 4, whether detectable or undetectable. The old complete early virologic response will now be W12U, denoting a week 12 unquantifiable HCV RNA level.

For trials with a lead-in (LI) period at, for example, weeks 0 to 4, and unquantifiable levels at week 8 (the old rapid virologic response), the new nomenclature would specifically refer to it as LI4w-W8U. Each term would be appended with TD or TND to denote whether target HCV RNA was detected or not detected.

One holdover from the current system is sustained virologic response (SVR).
"We decided to keep SVR...but it will be sustained virologic response with a bracket after it" to denote how long the response has been sustained, Dr. Jensen noted. "We're going to keep [it] because I think that's a concept that will be consistent with future therapies."

Having a uniform reporting system will allow the comparison of results across clinical trials. In addition, the system will be able to adapt as virologic response times become shorter. Beyond clinical trials, specific terminology will aid in the development of treatment guidelines for clinical practice.
The panel has submitted a manuscript for publication. Dr. Jensen hopes that industry will adopt the system for their clinical trials and that journals will require the system as the accepted nomenclature. The US Food and Drug Administration and the European Medicines Agency, as part of the HCV DrAG working group, have stated that they would like the nomenclature to be adopted.

Dr. Jensen predicts that in the future, if very effective drugs come along and therapy becomes standardized, many of the current or proposed measures of virologic response will go by the wayside, and patients will be treated with a fixed course of therapy with an expectation of cure, as is now common with antibiotics for many infections.

George Papatheodoridis, MD, associate professor of medicine and gastroenterology at the Medical School of Athens University, staff member at Hippokration General Hospital in Athens, Greece, and member of the EASL Governing Board Scientific Committee, told Medscape Medical News that he would like to see a consensus terminology adopted, but he does not expect that it will happen soon.
Nomenclature is not the only problem in defining a response, Dr. Papatheodoridis noted.

He referred to a presentation at the congress in which researchers found a discrepancy in the viral levels of 28% of the more than 1000 samples tested with a new polymerase chain reaction (PCR) assay and the original PCR assay. With the original assay, 75% of samples had undetectable HCV DNA; with the new assay, only about 50% did. Such a difference might be reflected in the "response-guided therapy we're using now with the telaprevir or boceprevir combination," he said.

With the drugs currently in development, the companies decide which assays to use to report their findings. "All the trials are controlled by the companies. They are not controlled by us," Dr. Papatheodoridis explained.

"Another problem, which is very relevant in clinical practice, is the timing of the HCV RNA determination," Dr. Papatheodoridis explained. We don't know if a difference of a few days is relevant. If you have some new excellent drug that achieves a 100% SVR 100%, you don't care, but these are not yet available.

Mark Thursz, MBBS, MD, professor of hepatology in the Department of Medicine at Imperial College London, United Kingdom and secretary general of EASL, agreed that measures of virologic response designed for interferon-based regimens are inadequate in an era of direct-acting antiviral drugs, "because the dynamics are much quicker now. A new set of specific targets are going to be really important when we assess how well the new drugs are working."

Dr. Jensen, Dr. Papatheodoridis, and Dr. Thursz have disclosed no relevant financial relationships.
The International Liver Congress 2012: Abstract 897. Presented April 20, 2012.

http://www.medscape.com/viewarticle/763459
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Friday, May 4, 2012

Hepatitis C News - Weekly Rewind

Hello Folks,
Its the end of the week already, where does the time go? On the blog today is a small rewind of this weeks news, research and updates. Click here to view previous or future"HCV Weekly Rewind" articles.

This week coverage on the EASL continues at HIV and Hepatitis C, NATAP, Medscape and this blog with interim results on new and experimental hepatitis C drugs.

An interesting development which has been slowly emerging is the possible new standard for reporting SVR results on new HCV drug regimens in clinical trials.

SVR12 by researchers is now being compared to SVR24. As it stands SVR- (sustained viral response or cure) is determined by an undetectable viral load-(level of virus) 6 months after therapy is completed. Offered in this post today are  two excerpts and an article discussing SVR4 and SVR12 from the clinical data presented at the EASL, followed up by links to full results.

We begin with a few drug regimens in development presented at the meeting last month, for instance-Abbotts ABT-450/r and ABT-072.

Excerpt- SVR12 end point seen in the small pilot study.

In a pilot study of 11 treatment-naive noncirrhotic patients, 91% achieved a sustained virologic response at 12 weeks after the end of treatment (SVR12), and 82% had a sustained virologic response at 36 weeks (SVR36). 
"If these very late relapsers are just 1% or 2%, then it will be of no clinical relevance.... If it's really 1 of 11 (so close to 10%), these late relapsers will be very important," he said. "Because these are new regimens, we don't know how the responders will behave in the long term, so I think the SVR12 should be the gold standard for reporting the results of the trials. [In addition], all trials should still have at least 1 HCV RNA follow-up...1 year after these SVR12 determinations."

View complete article @ Medscape-Two Oral Drugs Clear HCV Without Interferon- by Daniel M. Keller, PhD.

Next up is GS-7977 from Gilead Sciences and the ATOMIC and PROTON trials-view full data @ Medscape.

Excerpt; Mark Thursz, MBBS, MD comments in the article on SVR4 data and the FDA's interest in SVR12 as an end point........

Session moderator Mark Thursz, MBBS, MD, professor of hepatology in the Department of Medicine at Imperial College, London, United Kingdom, and secretary general of the European Association for the Study of the Liver, who was not involved in the ATOMIC trial, said during a news conference that SVR24, an absence of viremia for 6 months after the end of treatment, has been the standard definition of cure until recently. Now, "we've started to become used to SVR12 as an end point. I understand that the FDA [US Food and Drug Administration] is now interested in SVR12 if it can be subsequently established as meaning a cure," he said. 
"Now the companies are coming to us with SVR4 data.... SVR4 certainly predicts the final outcome. It may not be quite the same as the cure rate, the SVR24 rate, but it's pretty close and gives us a very good indication," Dr. Thursz explained. The implication is that when abstracts are submitted to meetings, "SVR4 is something that we have to take seriously...whereas previously we would regard [the results] as merely interim data," he said.

In the below article we have yet another reason to take SVR4  durability seriously, according to three  GS-7977 clinical trials; PROTON, ATOMIC, and ELECTRON- "100% of the patients with a SVR at week 4 maintained the SVR at week 24, and that none of these patients has had a relapse of the infection."

More Ways to Treat HCV Infection and Measure Response
April 23, 2012

Download PDF

Press Highlights Section Editor:
Grace L. Su, MD, University of Michigan Medical School
Story By:Kristine Novak, PhD, Science Editor, AGA Journals

New approaches to treating patients with hepatitis C virus (HCV) infection, and predicting how they will respond to therapy, were presented at the International Liver Congress (ICL) in Barcelona Spain last week.

The standard approach to assessing the efficacy of therapies for HCV infection involves determining if patients have a sustained viral response (SVR; an undetectable level of virus)at 24 weeks after therapy. It therefore takes about 6 months after therapy is completed to determine if a potential drug works.

Eric Lawitz et al. reported last Thursday that we might not need to wait that long. In studies of the antiviral agent GS-7977 (previously known as PSI-7977), all patients who had an SVR at 4 weeks after therapy ended maintained the response 24 weeks after therapy. This means that clinicians might be able to tell within a month after completion of therapy whether it was successful.

Lawitz et al. analyzed data from 3 large clinical trials (the PROTON, ATOMIC, and ELECTRON trials) of the uridine nucleotide analog GS-7977. The drug was being tested in interferon-containing and in interferon-free regimens for treatment-naïve patients with HCV genotype 1, 2, or 3 infections. They found that 100% of the patients with a SVR at week 4 maintained the SVR at week 24, and that none of these patients has had a relapse of the infection.

Lawitz et al. conclude that the absence of on-treatment viral breakthrough and lack of relapse among patients that have an SVR by week 4 indicate that GS-7977 suppresses HCV to a level that is beyond the range of current assays, and confirms that the virus is will not easily acquire mutations that make it resistant to the drug.

“We have to be careful in translating concordance versus cure” warned Lawitz after his presentation, but he proposes that SVR4 is a good biomarker of efficacy for these types of reagents.

Audience members pointed out that all the studies were performed in patients with low stages of fibrosis, and Lawitz agreed that further studies are needed to determine whether these findings will hold for patients with more advanced-stage hepatitis.

Mark Thursz, Secretary General of the European Association for the Study of the Liver (EASL),which sponsored the ICL, asked “Is SVR4 the new SVR24?” He says that it is something we have to take seriously.

Now For A Few Articles Of Interest This Week

More on HIV and Poverty in the U.S.
By Jessica Wapner
Posted: May 4, 2012
Many years ago, some friends of mine in Israel dug a hole. I don’t remember now what they were searching for, but they thought there was something a ways down, so they dug. It took a while, and in the…

FDA Must be Proactive About Postapproval Drug Safety: IOM
A new report instructs the FDA to evaluate a drug's risks and benefits throughout its life cycle and to adopt a centralized system for managing all information about a drug in a single document...

Debating the placebo as treatment
Marissa Fessenden on May 4th, 2012
The strange powers of the placebo effect are intriguing and getting stronger. And more research is examining this neurological quirk.
Placebos play an important role in research as controls to test the efficacy of medical interventions; a pill or procedure can only be considered effective if it works better than the placebo. But should placebos be part of actual treatment? Is a doctor who prescribes a sugar pill – even if it works to lessen symptoms – technically deceiving the patient?....

Growth Of Hepatocellular Carcinoma Halted By Combining Two MTOR Inhibitors
04 May 2012The combination of two inhibitors of protein mTOR stops the growth of primary liver cancer and destroys tumour cells, according to a study by researchers of the Group of Metabolism and Cancer at Bellvitge Biomedical Research Institute (IDIBELL)...

Cellular Energy May Be Depleted In Patients With Obesity And Diabetes By Increased Fructose Consumption
04 May 2012
Obese people who consume increased amounts of fructose, a type of sugar that is found in particular in soft drinks and fruit juices, are at risk for nonalcoholic fatty liver disease (NFALD) andmore its more severe forms...

Healthy You
Cirrhosis - Risks of Eating Raw Oysters
The risk factors for fibromylagia syndrome (FBS) among Hepatitis C patients

Research
The high comorbidity burden of the hepatitis C virus infected population in the United States

For Your Reading Pleasure
May Begins With Hepatitis C Disease Management, Drugs and Research

Awareness
Hepatitis C a latent legacy of baby boomers' youth
May Is Hepatitis Awareness Month

Off Topic
Watch the NEJM Documentary, Getting Better
This 45-minute documentary explores three remarkable stories of medical progress that have taken place over the course of the long history of NEJM. In 1812, we had no understanding of infectious disease, surgery was unsanitary and performed without anesthesia, and cancer was unrecognized. Two centuries later, this film tells the story of research, clinical practice, and patient care, and of how we have continued to get better over the last 200 years.




Enjoy your weekend !
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Wednesday, May 2, 2012

ABT-450/r plus ABT-072 - Two Oral Drugs Clear HCV Without Interferon

From Medscape Medical News

Two Oral Drugs Clear HCV Without Interferon

 Daniel M. Keller, PhD

May 2, 2012 (Barcelona, Spain) — Twelve weeks of treatment with a combination of 2 direct-acting antiviral drugs plus ribavirin achieved a sustained virologic response rate of more than 80% in patients chronically infected with genotype 1 hepatitis C virus (HCV), Eric Lawitz, MD, from Alamo Medical Research in San Antonio, Texas, reported here at the International Liver Congress 2012.

In a pilot study of 11 treatment-naive noncirrhotic patients, 91% achieved a sustained virologic response at 12 weeks after the end of treatment (SVR12), and 82% had a sustained virologic response at 36 weeks (SVR36).

Currently, the only approved regimens for the treatment of patients with genotype 1 HCV contain interferon. For patients who cannot tolerate interferon, there are no other options.

The 2 direct-acting antiviral drugs are ABT-450, a potent inhibitor of the HCV NS3 protease, and ABT-072 (Abbott Labs), a nonnucleoside inhibitor of HCV NS5B RNA polymerase. Both drugs are dosed orally once daily. ABT-450 is boosted with ritonavir (ABT-450/r) to maintain high ABT-450 exposure and to allow once-daily dosing.

This trial is the first to evaluate the 2 drugs plus ribavirin in an interferon-free regimen for the treatment of HCV genotype 1. The researchers enrolled only patients who were of the interleukin-28B CC genotype, which is the genotype most amenable to treatment with pegylated interferon and ribavirin, in case the trial regimen failed.

Patients were treated with ABT-450/r plus ABT-072 daily plus ribavirin for 12weeks and then followed for 48 weeks after the end of treatment. To be eligible for the study, patients had to be 18 to 65 years of age; had to have HCV genotype 1 infection for at least 6 months, no evidence of cirrhosis or bridging fibrosis, and no coinfection with hepatitis B or HIV; and had to be eligible for treatment with pegylated interferon plus ribavirin.

Baseline characteristics were similar in the the 2 groups (mean age, 56.4 years; mean weight, 79.6 kg). Mean HCV RNA level was 6.93 ± 0.22 log10 IU/mL, and all patients had HCV RNA levels above 800,000 IU/mL.

Rapid, Sustained Virologic Responses

All 11 patients achieved a rapid virologic response and an extended rapid virologic response. Sustained virologic responses at 12, 24, and 36 weeks occurred in 91%, 91%, and 82% of the cohort,respectively.

There were no virologic breakthroughs on therapy, but 2 patients relapsed after therapy ended — one at week 12 and the other at week 36.

All patients experienced adverse effects, but most were mild and included headache, nausea, fatigue, dry skin, and rash. One person had a fasting glucose level above 250 mg/dL, and 2 had indirect bilirubin elevations without concomitant transaminase elevations 1 week after treatment initiation, which resolved with continued dosing. The elevation was consistent with the known effect of ABT-450 on the OATP1B1 bilirubin transporter.

The were no study drug interruptions or discontinuations and no early trial discontinuations. There were also no deaths or serious adverse effects.

Session moderator George Papatheodoridis, MD, associate professor of medicine and gastroenterology at the Medical School of Athens University, staff member at Hippokration General Hospital in Athens, Greece, and member of the European Association for the Study of the Liver Governing Board Scientific Committee, told Medscape Medical News that in light of the small sample size, the 1 late relapse at 36 weeks may or may not be important.

"If these very late relapsers are just 1% or 2%, then it will be of no clinical relevance.... If it's really 1 of 11 (so close to 10%), these late relapsers will be very important," he said. "Because these are new regimens, we don't know how the responders will behave in the long term, so I think the SVR12 should be the gold standard for reporting the results of the trials. [In addition], all trials should still have at least 1 HCV RNA follow-up...1 year after these SVR12 determinations."

Dr. Lawitz reports financial relationships with Abbott, Achillion Pharmaceuticals, Anadys Pharmaceuticals, Biolex Therapeutics, Boehringer  Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, GlobeImmune, Idenix Pharmaceuticals, Idera Pharmaceuticals, Inhibitex Pharmaceuticals, Medarex, Medtronic, Merck, Novartis, Pharmasset, Roche, sanofi-aventis, Schering-Plough, Santaris Pharmaceuticals, Scynexis Pharmaceuticals, Tibotec, Vertex Pharmaceuticals, ViroChem Pharma, and ZymoGenetics. Dr. Papatheodoridis has disclosed no relevant financial relationships.

The International Liver Congress 2012: Abstract 13. Presented April 19, 2012.
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May Begins With Hepatitis C Disease Management, Drugs and Research

Greetings,

The "Digital Liver Disease Journal" is an official digital educational resource from the American Association for the Study of Liver Diseases.

The journals first issue was launched in February 2012 offering continuing medical education-CME, with video-abstracts, full data, and file downloads in either HTML or PDF formats. View the first issue here, and the new April issue  here.

The full text articles in the second volume-published online a few days ago can only be accessed through payment, however, all corresponding video abstracts and author interviews from the 2011 AASLD meeting remain open access.

Topic Highlights
Issues in selecting HCV-infected candidates for anti-viral treatment (pages 29–31)
Abstract
Watch the interview with the authors

Is there still a role for liver biopsy in managing hepatitis C virus infections? (pages 32–35)
Abstract
Watch the interview with the authors
Watch the video presentation of this article

Managing drug-drug interactions with boceprevir and telaprevir (pages 36–40)
Abstract
Watch the interview with the authors
Watch the video presentation of this article

Importance of patient education and monitoring among HCV-infected patients selected for anti-viral treatment (pages 41–45)
Abstract
Watch the interview with the authors

Predicting the response to the treatment of hepatitis C virus infection (pages 46–48)
Abstract
Watch the interview with the authors
Watch the video presentation of this article

Treatment options for anti-HCV treatment-experienced patients (pages 49–50)
Abstract
Watch the interview with the authors

Management of adverse events during the treatment of chronic hepatitis C infection (pages 54–57)
Abstract
Watch the interview with the authors
Watch the video presentation of this article

Drug resistance: Prevalence and clinical implications during the treatment of chronic hepatitis C infection (pages 58–61)
Abstract
Watch the interview with the authors

Reminder-
If you missed the link yesterday to the "2012 EASL Internet Symposium" at Viral Ed, you may be interested in the CME discussing key studies in HCV management and treatment.

Whats New At HCV Advocate ?

1. May 2012 Newsletter
 In This Issue:

HCV-Related Deaths and Cost-Effectiveness of Testing and Treatment by Alan Franciscus, Editor-in-Chief – Read about three important studies that examined the cost-effectiveness of testing the baby boomer population, treating them with current HCV medications and the future diease progression of the HCV population.

What You Don't Know, You Can Sell by Tracy Swan, TAG — An editorial by Tracy Swan from Treatment Action Group about the conscious decision by Merck to wait before conducting drug-drug interaction studies with boceprevir that put people at risk.

HCV Snapshots by Lucinda K. Porter, RN—In this month's column, Lucinda discusses the use of PEG/RBV for liver cancer, the liver and the brain and much more.

IN MEMORIAM: Michael Carden 1971-2012
—Alan Franciscus, Editor-in-Chief

HealthWise: May is Hepatitis Awareness Month by Lucinda K. Porter, RN—In this month's HealthWise column, Lucinda writes about awareness and the first ever national HCV testing day.

Boceprevir and Telaprevir Improve Cure Rates for HIV/HCV Coinfected People by Liz Highleyman—Liz writes about some of the information presented at this year's EASL conference, in particular about the treatment of HCV with boceprevir and telaprevir in people who are coinfected with HIV and HCV. 

2. Blog: EASL 2012 —Read about the important news about studies on HCV treatment that were presented at EASL.

3. May 2012 HBV Journal Review by Christine M. Kukka—Stay updated on the latest HBV information. Below is just a small sample of the articles summarized in this month’s review:

Hepatitis B plus a Family History of Liver Cancer Increases Cancer Risk 70-Fold

Researchers Suggest Tears and Saliva May Transmit HBV Infection

REVEAL Study Shows Links between HBV DNA and Liver/Pancreatic Cancers

Telbivudine Cuts Mother-to-Infant Hepatitis B Transmission to Zero
and more....................

New From Hep C Challenge
View 2012-2011 Monthly Literature Reviews
At CAP Hepatitis C Literature Review

May 2012 Abstracts
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New Antivirals Show Poor Safety in Hepatitis C With Cirrhosis

From Medscape Medical News
New Antivirals Show Poor Safety in HCV With Cirrhosis
Daniel M. Keller, PhD

May 2, 2012 (Barcelona, Spain) — Two relatively new direct-acting antiviral drugs have poor safety profiles in patients with hepatitis C virus (HCV) and cirrhosis, including a high rate of serious adverse events leading to study discontinuation. However, the efficacy of the drugs is good, as evidenced by high rates of on-treatment virologic responses, Christophe Hézode, MD, from Hôpital Henri Mondor in Créteil, France, reported here at the International Liver Congress 2012.

In phase 3 trials of the 2 drugs — telaprevir and boceprevir — rash, pruritus, and anemia were reported with telaprevir, and anemia and dysgeusia were reported with boceprevir. However, those trials included a relatively small number of patients with cirrhosis. A French compassionate-use program allowed the early use of these 2 protease inhibitors before they were approved for patients with cirrhosis, who were entered into a national multicenter registry to prospectively collect clinical data and biological specimens.

An interim analysis evaluated the safety and efficacy of the drugs in these patients who received at least 16 weeks of antiviral treatment (n = 455). The patients had compensated cirrhosis and had relapsed after previous treatment or were partial responders (defined as having had a decrease in HCV RNA of at least 2 log10 IU/mL at week 12 of therapy).

Telaprevir patients (n = 296) received 12 weeks of telaprevir with pegylated interferon (pegIFN) plus ribavirin and then continued only the pegIFN/ribavirin out to week 48. Boceprevir patients (n = 159) received pgIFN/ribavirin for 48 weeks, during which they also received boceprevir for weeks 4 to 48. Both groups were followed for virologic response after week 48.

The telaprevir and boceprevir groups were similar at baseline; mean age was 57 years, HCV RNA level was 6.5 log10 IU/mL, mean hemoglobin was 14.4 to 14.8 g/dL, mean neutrophil count was 3.2 to 3.3 × 109/mm3, and mean platelet count was 150,000/mm3.

High Serious Adverse Event Rate

"The rate of serious adverse events was high, around 50%, with early discontinuation due to severe adverse events observed in 14% of the patients," Dr. Hézode said.

"The second message is that 6 patients died — 2% of the cohort. The main reasons for these deaths were sepsis and hepatic decompensation" that was probably related to interferon, not telaprevir.

A third safety signal was the "difficult management of anemia," requiring the use of recombinant erythropoietin or transfusions, he explained.

Dr. Hézode said that in the boceprevir group, "the serious adverse event rate was high, around 40%, and early discontinuation due to serious adverse events was observed in 7% of patients." Two patients died from sepsis. Hepatic decompensation occurred in 4.4% of patients. Significant anemia occurred in one third of patients, two thirds required recombinant erythropoietin, and 10.7% received transfusions.

Dr. Hézode presented efficacy data on boceprevir, which was fairly good; 37% achieved undetectable HCV RNA levels at week 8 in an intention-to-treat analysis, rising to 58% at week 12 and 61% at week 16.

He concluded that the safety profile of these 2 direct-acting antiviral drugs in compensated cirrhotic patients is poor, but virologic responses are good. The high rate of serious adverse events (38.4% to 48.6%) was much higher than in phase 3 trials (9% to 14%).

Dr. Hézode recommended that patients with cirrhosis be treated cautiously with telaprevir or boceprevir and that they be monitored carefully, especially in light of the high incidence of anemia and its poor response to erythropoietin administration.

Session moderator George Papatheodoridis, MD, associate professor of medicine and gastroenterology at the Medical School of Athens University, staff member at Hippokration General Hospital in Athens, Greece, and member of the European Association for the Study of the Liver Governing Board Scientific Committee, told Medscape Medical News that "we were surprised by that high rate of so many serious adverse events, and even deaths, but I believe...they had included many patients with, in fact, contraindications to treatment."

He cited, for example, a low platelet count as a contraindication to interferon. "They went beyond the official indications, beyond the inclusion and exclusion criteria that were present in the phase 3 trials. I believe this is why they had such high rates of serious adverse events," Dr. Papatheodoridis said.

He noted that the number of platelets or neutrophils is a laboratory marker that reflects the severity of liver disease. "These were patients with very advanced liver disease who...should not have been treated with interferons," he said. "If you add the [protease inhibitor], which has more side effects, of course the safety profile will be worse."

Dr. Papatheodoridis said the investigators should do "the easy subanalysis" of patients with and without contraindications or who met or failed to meet prespecified criteria for entry into the trial, which Dr. Hézode said he plans to do.

Although there were no deaths in the telaprevir or boceprevir phase 3 trials, it is now obvious that it is very dangerous to use these drugs in such advanced patients.

"The usual indications are the indications for interferon — the inclusion criteria," Dr. Papatheodoridis said.

"For the new drugs, the only new contraindication might be other drugs that the patients take for other diseases because they might have drug–drug interactions."

Dr. Hézode and Dr. Papatheodoridis have disclosed no relevant financial relationships.

The International Liver Congress 2012: Abstract 8. Presented April 19, 2012.
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Tuesday, May 1, 2012

2012 EASL On Demand Internet Symposium


The much anticipated - 2012 EASL Internet Symposium at Viral Ed is up and ready to view.

Program Overview
This Internet symposium will review and discuss the key studies on chronic hepatitis C management and treatment presented at EASL. The symposium will feature four well-known and recognized thought leaders in the HCV field, with three serving as presenting faculty/discussants and one as program moderator.



 Advances in Chronic Hepatitis C Management and Treatment
Ready To View
*Free registration required
,

Slide-Deck Ready To View


Online Expert Poster Review and Discussion
Still In Progress

The 47th Annual EASL:
Advances in Chronic Hepatitis C Management and Treatment  begins here.


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GS-7977 Induces Rapid, Durable Drops in Viral Load

Medscape Medical News from:
The International Liver Congress 2012

This coverage is not sanctioned by, nor a part of, the European Association for the Study
of the Liver.

From Medscape Medical News

New HCV Drug Induces Rapid, Durable Drops in Viral Load
Daniel M. Keller, PhD

April 30, 2012 (Barcelona, Spain) — In 3 phase 2 trials of GS-7977, there was a concordance between the sustained virologic response (SVR) 4 weeks after the end of therapy (SVR4) and SVRs at 12 and 24 weeks after therapy (SVR12 and SVR24) in treatment-naive patients infected with hepatitis C virus (HCV) genotypes 1, 2, or 3.

No patient relapsed after posttreatment week 12, and 99% of patients with SVR4 for whom posttreatment week 12 data were available achieved SVR12, Eric Lawitz, MD, from Alamo Medical Research in San Antonio, Texas, reported here at the International Liver Congress 2012.

GS-7977 (formerly PSI-7977) is a specific nucleotide analogue inhibitor of HCV NS5B RNA polymerase and is taken orally once daily. Previous reports have shown that it has broad antiviral activity against HCV genotypes 1, 2, and 3, with or without interferon, in treatment-naive patients, and has a high barrier to the development of viral resistance.

The aim of the study was to evaluate concordance between SVR4 and SVR12 or SVR24 among treatment-naive patients taking GS-7977 400 mg daily in the PROTON (n = 144), ELECTRON (n = 120), and ATOMIC (n = 332) phase 2 clinical trials. The trial protocols differed somewhat, but in general were various combinations and durations of GS-7977, pegylated interferon (Peg-IFN), and ribavirin.

In the PROTON and ATOMIC trials, depending on viral genotype, patients received GS-7977 plus Peg-IFN/ribavirin for 12 weeks followed by Peg-IFN for 12 weeks, Peg-IFN/ribavirin alone for 48 weeks, GS-7977 plus Peg-IFN/ribavirin for 12 or 24 weeks, GS-7977 plus PegIFN/ribavirin for 12 weeks followed by 12 weeks of GS-7977 alone or by GS-7977 plus ribavirin.
In the ELECTRON trial, some patients with genotypes 2 or 3 virus received similar combinations but only out to 12 weeks. Other patients with genotypes 1, 2, or 3 received GS-7977 plus ribavirin for 12 weeks.

The analysis involved only patients treated with GS-7977 400 mg in combination with interferon, ribavirin, or both for at least 4 weeks who had SVR4 plus SVR12 or SVR4 plus SVR24 data available. Of the 596 patients in the 3 studies, 259 (43%) were eligible for analysis.

At baseline in all treatment groups, mean age ranged from 43 to 52 years, and most patients were white, male, had similar body mass indices (mean, 26 to 28 kg/m²), and had interleukin-28B genotype non-CC. Mean baseline HCV RNA levels were mainly in the range of 6.3 to 6.7 log10 IU/mL.
Dr. Lawitz presented results for virologic response at the end of therapy and for SVR4, SVR12, and SVR24.

"If we look at all regimens and look at the concordance between SVR4 and SVR12, we can see that 249 of the 251 [patients] were concordant between SVR4 and SVR12 — a concordance rate of 99%," he said. "If we look at concordance between SVR4 and SVR24, we can see that although the numbers are smaller, there is complete concordance — all 107 patients who had an SVR4 achieved an SVR24.... The concordance held, irrespective of the presence or absence of interferon. However, the dataset is fairly small in the noninterferon arm, limiting conclusions."

Dr. Lawitz concluded that "much of the concordance is due to the high response rates observed across all treatment groups. To date, relapse after week 4 is infrequent and was only observed in patients who received a peg-interferon-containing regimen."

Session moderator George Papatheodoridis, MD, associate professor of medicine and gastroenterology at the Medical School of Athens University, staff member at Hippokration General Hospital, in Athens, Greece, and a member of the European Association for the Study of the Liver Governing Board Scientific Committee, told Medscape Medical News that GS-7977 "is a very interesting, very promising molecule. It seems to be rather safe and very effective, even in combination with ribavirin." Dr. Papatheodoridis was not involved in any of the studies.

In terms of new drugs to treat HCV, he said, "some of the new molecules are very genotype-specific.... Most of the protease inhibitors are developed to work only for genotype 1; some of them work for genotype 2, but not 3 and 4. The nucleoside polymerase inhibitors seem to work better across almost all genotypes, so this is the only class [of drug] that is not that genotype-specific."

Dr. Papatheodoridis wondered about the use of SVR4 as a standard efficacy measure. "I don't think that SVR4 will and should be the standard for SVR," he told Medscape Medical News. "Of course, we know that the FDA and most of the physicians have now accepted SVR12. So probably...SVR12 is going to be the standard for reporting trials in the near future. Still, with all these combinations, patients should have at least 1 examination, maybe 6 months or 12 months after SVR12, so we can be sure that this SVR remains over time. I think that SVR12 is going to be the standard from now on, but the patients treated with the new regimens should be followed for a bit longer."

He admitted that SVR4 looks predictive of later sustained responses. "You expect most of the patients to relapse soon after stopping treatment [if they are going relapse]. Of course, SVR4 is reasonable; we know and we expect that it is going to be associated with SVR12 and SVR24. There is no rush to decide the SVR just 4 weeks after treatment.... We should be sure that we eradicated the virus," he cautioned.

Dr. Lawitz reports financial relationships with Abbott, Achillion Pharmaceuticals, Anadys Pharmaceuticals, Biolex Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, GlobeImmune, Idenix Pharmaceuticals, Idera Pharmaceuticals, Inhibitex Pharmaceuticals, Medarex, Medtronic, Merck, Novartis, Pharmasset, Roche, sanofi-aventis, Schering-Plough, Santaris Pharmaceuticals, Scynexis Pharmaceuticals, Tibotec, Vertex Pharmaceuticals, ViroChem Pharma, and ZymoGenetics. Dr. Papatheodoridis has disclosed no relevant financial relationships.

The International Liver Congress 2012: Abstract 7. Presented April 19, 2012.

Conference News
Medscape Gastroenterology © 2012 WebMD, LLC

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Sunday, April 29, 2012

EASL- COFFEE INTERFERES WITH HCV REPLICATION IN VITRO BY INHIBITION OF WNT SIGNALING

COFFEE INTERFERES WITH HCV REPLICATION IN VITRO BY INHIBITION OF WNT SIGNALING
Speaker: Amelie Keller
Author: A.D. Keller1*, K. Singethan2, A. Wuestenberg1, V. Lohmann3, R. Bartenschlager3, M. Dandri4, U. Protzer2, G. Tiegs1, G. Sass1
Affiliation: 1Institute of Experimental Immunology and Hepatology, University Medical Center Hamburg Eppendorf, Hamburg, 2Institute of Virology, Technische Universität München (TUM), Munich, 3Department of Molecular Virology, University of Heidelberg, Heidelberg, 4Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. *amelie_keller@web.de

Background and aims:
 Coffee is the worldwide most frequently used legal psychoactive substance. On the other hand its consumption has been shown to decrease the risk of fibrosis formation and to improve anti-viral effects of interferon alpha/ribavirin treatment of HCV patients. We investigated effects of regular and decaffeinated coffee and coffee ingredients on HCV replication and infection in vitro.

Methods:
 To investigate effects of coffee on HCV replication, infectious as well as subgenomic replicon cell culture systems were used. Cells were incubated in the presence of regular or decaffeinated coffee or the coffee ingredients caffeine or chlorogenic acid. Effects on HCV replication and wnt pathway activity were measured by luciferase reporter assay or real time RT-PCR.

Results:
Coffee reduced HCV replication with regular coffee having a more pronounced effect. Coffee significantly reduced HCV replication at concentrations achievable by coffee consumption, while caffeine as well as caffeine degradation products interfered with HCV replication at high concentrations (about 100 µM or more). Chlorogenic acid did not reduce HCV replication up to concentrations of 200 µM. Wnt pathway activity was found to be markedly increased in HCV replicating cells in comparison to the background cell line Huh7. Inhibition of wnt pathway activity, e.g. by use of siRNA directed against beta-catenin, interfered with HCV replication. Likewise, coffee-but not caffeine-incubation reduced wnt pathway activity, as detected by reporter assays or real time RT-PCR for beta-catenin, conductin or the wnt pathway promoter kinase CK2. In addition to its inhibitory effects on HCV replication, two hours of pre-incubation with coffee decreases subsequent HCV infection and modulated HCV receptor expression on primary human hepatocytes.

Conclusions:
 Coffee interferes with HCV replication by inhibition of the wnt signaling pathway which might represent a novel target for HCV therapy. Coffee also interferes with HCV infection in vitro which might reduce virus spreading within the infected liver.

http://mobile.ilcapp.eu/EASL_161/poster_24038/program.aspx
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Friday, April 27, 2012

EASL 2012 - Weekend Reading

'Reading', a painting by Kuroda Seiki

Most weekends this blog offers up a few substantial links to relevant HCV information, click here for previous "Weekend Reading" articles.

The 47th European Association for the Study of the Liver - EASL  
As the annual meeting ends educational sites related to liver disease and hepatitis begin the process of putting together key data on hepatitis C and treatment.


 Viral Ed offers continuing medical education-CME and will bring us an Internet symposium discussing important highlights of the meeting. The program -"The 47th Annual EASL: Advances in Chronic Hepatitis C Management and Treatment" will soon be ready to view, make sure you register for the upcoming 1.5-hour program by clicking here. 

As a side note - The 19th Conference on Retroviruses and Opportunistic Infections (CROI) Internet Symposium is also on the site.

Clinical Options is still in the process of putting up slides but 20 capsule summaries are ready to view, click here to register.

Additional coverage on the meeting is available at NATAP, HIV and Hepatitis C, hepmag and articles  can be read at Medpage Today, aidsmap, Medscape Medical News and Hepatitis C New Drugs and Liver Health.

New online; Advances in HCV Treatment Volume 20 Issue 1 April/May 2012 - Perspective Advances in the Treatment of Hepatitis C Virus Infection, download PDF here.

Summary
The current era in HCV treatment is reminiscent of the transformation of HIV treatment that occurred in the mid-1990s. With the new HCV treatments, cure and complications occur more frequently. We can make smart applications of the treatments available to us right now in some patients, and we await tomorrow’s treatments for other patients. As with the first wave of HIV medications in the potent antiretroviral era, the new HCV drugs offer huge advantages but also present substantial challenges.

Sadly, as most of you know the experimental hepatitis C drug combination of daclatasvir and GS-7977 we read so much about during the meeting may not be entering into phase III clinical trials. The drug companies Bristol-Myers Squibb-daclatasvir and Gilead-GS-7977 may forgo working together on further development of the two drug combo. This is such a disservice to the 170 million individuals worldwide - 3.2 million people in the US- suffering with hepatitis C.  According to the CDC in the US there are an estimated 30,000 new acute infections a year, and 8000-10,000 deaths. This disease has rapidly surpassed HIV as a cause of death in the United States.

Please sign the online petition urging Gilead and BMS to collaborate on the promising experimental treatment for hepatitis C.

This April podcast comes to you from the nationally syndicated public radio program The Health Show  on WAMC with host Bob Barrett and guest physician discussing both hepatitis C, treatment and Sjogren’s Syndrome, a disease - although rarely - seen in hepatitis C patients.


Enjoy Your Weekend !
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