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May 30, 2008

Optimism Swells After Liver Conference

Several researchers at the May 2008 Digestive Disease Week in San Diego reported encouraging progress in their mission to extinguish liver disease. One of the advancements announced includes monitoring dendritic cells to determine which Hepatitis C patients will fare well during treatment.

New Hope for Liver Diseases

By Kathleen Doheny
HealthDay Reporter
Friday, May 23, 2008; 12:00 AM

www.washingtonpost.com

FRIDAY, May 23 (HealthDay News) -- Human liver cells have been generated from embryonic stem cells using a new model, hopefully opening the door to help scientists screen for harmful side effects of new drugs before they are used in patients.

That was one of several reports on advances against liver diseases that were presented this week at Digestive Disease Week 2008 in San Diego.

Other presentations involved ways to predict which patients with hepatitis C might benefit from long-term antibiotic therapy and information about how monitoring the body's viral load in hepatitis B patients may help predict liver cancer.

Scientists from the University of Edinburgh, Scotland, reported they had efficiently generated human liver cells from embryonic stem cells without the problems that have plagued scientists in the past. The new model is unique, said Dr. David Hay, a senior fellow at the university's MRC Centre for Regenerative Medicine, who spoke at a press conference Tuesday.

His team developed a model that allows them to focus on key enzymes which are crucial in drug metabolism. Other clinical applications, he said, include the fact that the liver cells generated in vitro could be used in bioartificial devices, helping maintain normal function when the liver fails.

Down the road, said another investigator, Dr. Philip Newsome, the hope is that the cells could be used in liver transplantation.

The advance was praised by the press conference moderator, Dr. John M. Vierling, chief of hepatology at Baylor College of Medicine, in Houston.

The team produced "highly differentiated cells that maintain function," Vierling said, a feat that has thus far proved elusive to others working on the effort. "It is an extraordinarily rich advance to be exploited in many ways," he added.

Predicting which patients with chronic hepatitis C infection, another liver ailment, will respond to treatment may be done by monitoring the dendritic cells, the cells that are the most potent stimulator of the immune system's T-cells, said Dr. John Mengshol, a fellow in the department of gastroenterology and hepatology at the University of Colorado Health Sciences Center, in Denver.

Treatment for hepatitis C virus routinely involves 48 weeks of combination antiviral therapy. Side effects include flu-like symptoms, and treatment is successful in only half of patients.

So, predicting who will and won't respond would be helpful. Mengshol and his colleagues evaluated 64 patients with hepatitis C virus of the genotype 1, the most common strain and the most difficult to treat.

Researchers have found that therapy affects the dendritic cells differently. Mengshol's team studied blood samples from each patient before treatment and at 24 weeks after starting it. They looked at the population of two different types of dendritic cells, among other factors.

Levels of one type of dendrite cells normalized in those who responded to the treatment, while levels of those who did not respond did not.

Why some patients respond to therapy and others don't has been an ongoing mystery, Mengshol said. Monitoring the dendritic cells may help doctors determine who might respond to therapy.

In another study, Dr. Uchenna Iloeje, director of virology for Global Clinical Research at Bristol-Myers Squibb Co., reported that monitoring the viral load of hepatitis B virus in patients with that disease is a significant predictor of who will be likely to get liver cancer.

In the study, researchers followed more than 3,500 patients for 11.5 years, Iloeje said.

"Over time, those at highest risk of liver disease had a sustained hepatitis B load," he said.

The liver is the largest organ inside the body. It changes food into energy, cleans alcohol and poisons from the blood, and makes bile, a liquid that aids digestion.

More information

For more on liver diseases, go to Medline Plus.

SOURCES: John M. Vierling, M.D., professor, medicine and surgery, chief, hepatology, Baylor College of Medicine, Houston; John Mengshol, M.D., Ph.D., fellow, University of Colorado School of Medicine, Denver; Uchenna Iloeje, M.P.H, M.B.B.S., director, virology, Global Clinical Research, Bristol-Myers Squibb; May 20, 2008, presentations, Digestive Disease Week 2008, San Diego

Posted by Editors at 02:40 PM --- Printer-friendly version

HCV Cure Associated with Early Drop in Viral Load

Australian researchers find that the suppression of Hepatitis C viral load within the first month of beginning treatment is a good predictor of defeating the virus - regardless of co-infection with HIV.

Overcoming virus early beats hepatitis

Adam Cresswell, Health editor | May 24, 2008

www.theaustralian.news.com.au

DRIVING down the number of circulating copies of the hepatitis C virus to undetectable levels in the earliest stages of infection makes it highly likely that the patient will eventually be cured - even among patients who are also infected with HIV.

The findings, the interim results from an Australian study presented to a recent international conference in Italy, suggest that rapid virological response - or RVR, the term used to indicate successful suppression of viral load within four weeks of starting treatment - is just as good a predictor of eventual cure among patients suffering acute hepatitis C infection as it is already known to be among chronically infected individuals.

In addition, the trial - which is still continuing - suggests new treatment options for difficult-to-treat groups such as people with HIV and injecting drug users. Unlike most hepatitis C treatment studies, this research included significant numbers of HIV patients and injecting drug users, and the findings showed RVR was just as good at predicting eventual cure in these as in other patients.

The Australian Trial in Acute Hepatitis C, known by its acronym ATAHC, was funded by the US National Institutes of Health. The interim findings were presented as a poster at the recent annual scientific meeting of the European Association for the Study of the Liver in Milan, where it was voted into the top 10 per cent of the more than 800 poster presentations at the meeting.

An estimated 264,000 Australians have been exposed to hepatitis C, a blood-borne virus that attacks the liver and left untreated can lead to liver inflammation, cirrhosis and eventually cancer.

Although 25 per cent of people clear the virus naturally, the prognosis for the remaining 75 per cent is more difficult as most will usually experience symptoms such as debilitating fatigue, pain and nausea.

While cure is possible with drug therapy, the drugs are quite toxic and hard to tolerate. Treatment also lasts a year and only works in fewer than 50 per cent of cases. Co-infection with HIV makes it even harder to eradicate hepatitis C.

Sydney-based hepatitis expert Greg Dore, a co-author of the study and who attended the Milan conference, said the message from the ATAHC findings was that if doctors could drive viral levels down to undetectable levels early "you can get incredibly good response rates".

While 107 patients in the study elected to have treatment for acute hepatitis C, 84 patients continued to the point where they had data on their progress after four weeks of treatment. Among the 26 patients infected with HIV as well as hepatitis C, RVR, or complete viral suppression, was observed in 10 people (45 per cent), and in 28 out of the 58 patients infected with hepatitis C alone (48 per cent).

Those with high hepatitis C viral loads at the start of treatment, with more than 400,000 international units per millilitre of blood, were less likely to achieve RVR.

Finally, 53 patients were assessed for both RVR and for sustained virological response, or SVR, a longer-term measure that is often taken to mean the patient has been cured. All the participants who achieved RVR went on to achieve SVR, and even 59 per cent of those who did not achieve RVR went on to be cured later.

The study's authors concluded that patients treated for acute hepatitis C infection and who achieved RVR "are highly likely to achieve SVR, irrespective of HIV status".

"This is the largest study ever of an injecting drug-user population with early infection," said professor Dore, who is head of the viral hepatitis clinical research program at the Sydney-based National Centre in HIV Epidemiology and Clinical Research.

"We have shown that it is feasible to treat this group, many of whom have been recent injecting drug users, and get remarkably good outcomes.

"What we are looking at now is to apply to the NIH for another five years' funding, to look at the different strategies to optimise treatment outcomes in this group."

Dore's colleague doctor Gail Matthews said the high proportion of HIV-positive cases in the study participants, about one-third, "probably reflects a current increase in acute HCV in this population - predominantly acquired through sexual transmission and mirroring what is being reported from many centres in Europe".

"This has potential implications for public health messages in this group," she said.

Adam Cresswell's trip to the EASL conference in Milan was organised as part of the prize for winning the Professor Geoff Farrell Medal, a journalism award organised by Hepatitis Australia for writing about hepatitis C. Funding for the award was provided by the drug company Schering-Plough.

Posted by Editors at 02:37 PM --- Printer-friendly version

May 27, 2008

Wine and Liver Health

Although a study emerging from San Diego claims that a small amount of wine may protect the liver, the researchers admit that this is not true for those already living with liver disease. In fact, there are several more caveats to this surprising claim.

A little wine can be beneficial to liver, UCSD research finds

By Cheryl Clark
UNION-TRIBUNE STAFF WRITER
www.signonsandiego.com

May 22, 2008

Alcohol and your liver: not a happy couple, right?

Well, not exactly. A new UCSD study challenges conventional wisdom by suggesting one small glass of wine a day can reduce the risk of early-stage liver disease by one-half compared with drinking no alcohol.

People who drank beer or hard liquor, though, had more than four times the odds of getting fatty liver disease.

“This is a whole paradigm shift in our way of thinking about this disease,” said Dr. Jeffrey Schwimmer, a UCSD liver disease expert who admits to drinking more wine now – preferably red – than before he conducted this study.

Moderate wine drinking previously has been linked with protecting the heart. Now, Schwimmer said, “if one is going to use alcohol in a modest fashion for heart protection, this study suggests wine is not only safe for the liver, but may in fact be beneficial.”

Schwimmer's study does not explain exactly how wine protects the liver, but he suggested in an interview that the benefit might come from an ingredient in wine called resveratrol, or from a process related to the fermentation of grapes.

His report is published in the current issue of the journal Hepatology and was funded by divisions of the National Institutes of Health.

The condition Schwimmer studies is called non-alcoholic fatty liver disease, a condition found in 20 percent of adults, even those who drink little alcohol. The condition has no symptoms, but can be diagnosed when the liver has around 5 percent abnormal fat deposits. The normal amount is 1 percent.

In a quarter of those with fatty liver disease, the condition worsens to hepatitis or liver inflammation. And in 10 to 20 percent of those with hepatitis, scarring associated with cirrhosis occurs.

Before one rushes to the discount wine store, the study has several caveats. For starters, one must limit consumption to only 4 ounces a day, a little more than two shots' worth.

Second, people who already have liver disease should avoid alcohol at all costs.

Third, the study does not suggest that drinking more than 4 ounces further reduces the chance of liver disease. In fact, for most people, drinking more alcohol could raise the risk of other illnesses, such as cirrhosis of the liver and heart disease.

Schwimmer's study also is vulnerable to reporting error. It was based on examination of answers given to researchers between 1988 and 1994 by 15,000 adult Americans who had undergone a liver enzyme blood test called ALT.

ALT is not as accurate as liver biopsies in diagnosing fat in the liver, he acknowledged.

“Now we need to take the next step,” Schwimmer said. He plans to study people who have more symptomatic liver disease, including hepatitis or cirrhosis, not linked to heavy use of alcohol.

Posted by Editors at 02:15 PM --- Printer-friendly version

May 14, 2008

What You Must Know About Alcoholic Hepatitis

If you think one must be a heavy drinker to suffer from this condition, you ought to read this article. Discover the causes, risk factors and complications of alcoholic hepatitis. Share this information with others. After reading this, anyone with liver concerns may want to abandon intoxicating beverages altogether.

Alert to Alcoholic hepatitis

Daily Mirror Health Line
Compiled by Naveen Jayawardena
www.dailymirror.lk

Monday, May 12, 2008

Alcohol has long been associated with serious liver diseases such as hepatitis - inflammation of the liver. But the relationship between drinking and alcoholic hepatitis is complex. Only a small percentage of heavy drinkers develop alcoholic hepatitis, yet the disease can occur in people who drink only moderately or binge just once. And though damage from alcoholic hepatitis often can be reversed in people who stop drinking, the disease is likely to progress to cirrhosis and liver failure in people who continue to drink. For them, alcoholic hepatitis may be fatal.

Causes

· Genetic factors. Having mutations in certain genes that affect alcohol metabolism may increase your risk of alcoholic liver disease as well as of alcohol-associated cancers. Genetic factors may account for half of any person's susceptibility to alcohol-related disease.

· Other types of hepatitis. Long-term alcohol abuse worsens the liver damage caused by other types of hepatitis, especially hepatitis C. If you have hepatitis C and also drink - even moderately - you are more likely to develop cirrhosis than is someone who doesn't drink.

· Other diseases. People who drink alcohol are more likely to develop alcoholic hepatitis if they also have another disease that affects the liver, such as diabetes or iron overload (hemochromatosis) - a disorder in which the body stores too much iron.

· Obesity. Although most researchers agree that obesity makes alcoholic liver disease worse, exactly why this is so isn't clear. It may be that alcohol causes fatty tissue to produce certain hormones and cytokines - immune system proteins that increase inflammation.

· Malnutrition. Many people who drink heavily are malnourished, either because they eat poorly - often substituting alcohol for food - or because alcohol and its toxic byproducts prevent the body from properly absorbing and metabolizing nutrients, especially protein, certain vitamins and fats. In both cases, the lack of nutrients contributes to liver cell damage. It was once thought that malnutrition, rather than alcohol, caused alcoholic liver disease. Now, the relationship between the two appears more complicated. But it's certain that drinking leads to malnutrition, which damages the liver and contributes to some of the serious complications of alcoholic liver disease.

Risk factors

· Alcohol use. Consistent heavy drinking or binge drinking is the primary risk factor for alcoholic hepatitis, though it's hard to precisely define heavy drinking. Some experts believe that four or more drinks a day for men and two or more a day for women greatly increase the risk of liver damage. Moderate drinking is usually defined as no more than two drinks a day for men and one for women. But because people vary greatly in their sensitivity to alcohol, that amount may not actually be moderate for everyone. Whether certain types of alcohol cause more harm than others also is a matter of debate. Some experts believe that wine is less damaging than hard liquor is, although it may be that wine drinkers generally tend to have healthier lifestyles.

· Age. The effects of alcoholic hepatitis are most likely to show up after years of heavy drinking, but symptoms of disease can develop in people as young as 20.

· Your sex. Women are two to three times as likely to develop alcoholic liver disease as men are. It takes less alcohol to harm the liver in women, and when liver disease occurs, it progresses more quickly than it does in men. This disparity may result from differences in the way alcohol is absorbed and broken down. Because women tend to metabolize alcohol more slowly, their livers are exposed to the higher blood concentrations of alcohol for longer periods of time - with potentially greater toxicity. The slow rate of alcohol metabolism in women may be due to lower levels of stomach enzymes that break down alcohol, the effects of estrogen or even the size of a woman's liver.

· Genetic factors. Researchers have discovered a number of genetic mutations that affect the way alcohol is metabolized in the body. Having one or more of these mutations may increase the risk of alcoholic liver disease and liver cancer.

Complications

· Increased blood pressure in the portal vein. Blood from your intestine, spleen and pancreas enters your liver through a large blood vessel called the portal vein. If scar tissue blocks normal circulation through the liver, this blood backs up, leading to increased pressure within the vein.

· Enlarged veins (varices). When circulation through the portal vein is blocked, blood may back up into other blood vessels in the stomach and esophagus. These blood vessels are thin walled, and because they're filled with more blood than they're meant to carry, they're likely to bleed.

· Fluid retention. Alcoholic liver disease can cause large amounts of fluid to accumulate in your abdominal cavity (ascites).

· Bruising and bleeding. Alcoholic hepatitis interferes with the production of proteins that help your blood clot and with the absorption of vitamin K, which plays a role in synthesizing these proteins. As a result, you may bruise and bleed more easily than normal. Bleeding in the gastrointestinal tract is particularly common.

· Jaundice. This occurs when your liver isn't able to remove bilirubin - the residue of old red blood cells - from your blood. Eventually, bilirubin builds up and is deposited in your skin and the whites of your eyes, causing a yellow color.

· Hepatic encephalopathy. A liver damaged by alcoholic hepatitis has trouble removing toxins from your body - normally one of the liver's key tasks. The buildup of toxins such as ammonia can damage your brain, leading to changes in your mental state, behavior and personality.

· Cirrhosis. This serious condition, which is an insidious and irreversible scarring of the liver. Cirrhosis frequently leads to liver failure, which occurs when the damaged liver is no longer able to adequately function.

Copyright © Wijeya Newspapers Ltd.

Posted by Editors at 09:25 AM --- Printer-friendly version

May 13, 2008

15 Tips for Managing Interferon-Ribavirin Side Effects

Many people abandon this challenging HCV treatment mid-course. Here are 15 ways to help manage the side effects of Hepatitis C combination therapy, to help patients' likelihood of completing the extremely challenging treatment. Share this article among patients contemplating and/or already undergoing chemotherapy for Hepatitis C, so they can help increase their likelihood of conquering the virus.

by Nicole Cutler, L.Ac.

Although it affects an estimated four to five million Americans, there is still no easy formula to eliminate the Hepatitis C virus (HCV). At best, infected individuals have a 50 percent chance of triumphing over the virus by enduring standard combination therapy, a notoriously challenging treatment with pegylated interferon and ribavirin medications. Most experts believe that the success rate of these drugs would be much higher without the burden of their potentially serious side effects. In cooperation with a physician, those with HCV who can manage standard combination therapy’s side effects are more likely to complete the drug regimen at full strength – and thus have a better chance of ridding the virus from their body.

Especially apparent in the first several weeks of treatment, the side effects of these drugs range from mild to severe. Managing these effects can be simple, involving lifestyle modifications, logical home remedies and taking some routine medications. Beyond these basics, working with a knowledgeable physician is important for customizing a plan to help someone manage their side effects.

The side effects from interferon and ribavirin therapy often lead to lowered dosages or even discontinuation of these drugs. Physicians agree that the more a dosage is reduced, the less of a chance the therapy has at successfully killing HCV. However, dose reduction or discontinuation of interferon or ribavirin may be indicated immediately if severe side effects develop.

Fifteen suggestions to discuss with your physician for managing the most common side effects of combination therapy are outlined below:

1. Getting a full night’s sleep helps the body recover from physical and emotional stressors. Being fully rested lessens the side effects of fatigue, headache, fever, myalgia (muscle pain), irritability and insomnia.

2. Keeping hydrated is helpful to counteract the drying properties of combination therapy. Keeping hydrated is advised to improve fatigue, headache, fever, myalgia and dry mouth.

3. Eating well-balanced meals helps the body bounce back from fatigue, headache, fever and myalgia.

4. Engaging in regular exercise keeps your circulation going and thus helps prevent fatigue, headache, fever and myalgia.

5. Taking a hot bath or using hot packs is recognized for helping relieve myalgia.

6. Taking acetaminophen (Tylenol) or NSAIDS can reduce fatigue, headaches, fever, myalgias or liver pain. However, dosage and safety considerations must be confirmed by your doctor since these drugs may place an additional burden on the liver.

7. Include ginger in your day by drinking it in tea, ale or snacking on ginger baked goods to relieve nausea.

8. Taking ribavirin with food and eating small, frequent meals helps ease ribavirin-related nausea.

9. Prochlorperazine (compazine) may stop nausea but should only be done under a physician’s guidance.

10. Avoiding stimulants like caffeine at night can reduce insomnia and irritability.

11. Practicing relaxation techniques, such as taking a deep breath and counting to ten, can significantly help reduce irritability.

12. Taking selective serotonin reuptake inhibitors (SSRIs) have been proven effective in treating the depression associated with interferon therapy for certain individuals. The additional side effects of SSRIs and treatment guidelines must be carefully evaluated by your physician.

13. Sharing feelings with friends, family or a support group can help many people cope with the irritability and depression often accompanying HCV therapy.

14. Being gentle with your hair can help minimize hair loss. This includes not pulling on or braiding the hair, avoiding vigorous combing or brushing and only using natural (not harsh) hair products.

15. Avoiding hot or spicy foods minimizes mouth irritation. For those dealing with the side effects of a dry mouth or mouth sores, avoiding these types of foods is a must.

Some of these tips for managing side effects are easily accomplished at home while others require collaboration with your physician. However it is accomplished, reducing side effect severity helps people endure a full course of combination therapy, a feat that increases their odds of eliminating the Hepatitis C virus.

References:

www.clevelandclinic.org, Managing Side Effects of Hepatitis C Treatment, The Cleveland Clinic Department of Patient Education and Health Information, 2008.

www.hepatitis.va.gov, Clinical Manual: Interferon and Ribavirin Treatment Side Effects, United States Department of Veteran Affairs, 2008.

www.hepcawareness.net.au, Treatment Side Effects, Australian Hepatitis Council, 2008.

Posted by Editors at 11:12 AM --- Printer-friendly version

May 12, 2008

New Mexico Offers Free Hepatitis C Hotline

Finally being recognized as the widespread, public health problem that it is, the New Mexico Department of Health has taken a giant step forward to help people with Hepatitis C. By launching a new, toll-free phone number, locals concerned about Hepatitis C can get some confidential, practical, expert advice.

Department of Health launches toll-free Hepatitis C number

Sun-News report
Article Launched: 05/06/2008 10:03:24 AM MDT

www.lcsun-news.com

SANTA FE -- The New Mexico Department of Health has launched a new toll-free number that will make it easier for patients with hepatitis C to access services and learn how to fight the disease. Department of Health staff answers the confidential, toll free number from 8 to 5 p.m. Monday through Friday at 1-888-DOH-HepC (364-4372). Callers can also leave a confidential message that will be returned by Department staff.

"The number will help providers connect patients with hepatitis C services," said Ray Stewart, the Department's director of public health services in southwestern New Mexico. "Individuals who are at risk for hepatitis C can also call to find out where they can get tested."

Project ECHO is a partnership between the Department of Health, the University of New Mexico Health Sciences Center, the New Mexico Corrections Department, and the New Mexico Primary Care Association. The project, which began in 2003, provides medical providers across the state with expert advice through telehealth sessions on treating their patients.

Telehealth uses live videoconferencing through the internet and has the potential to close gaps in healthcare access many New Mexicans face due to the lack of medical and behavioral health specialists in their area. Project ECHO also covers other chronic diseases such as asthma, arthritis, obesity, depression, and substance use disorders.

In recognition of World Hepatitis Day on May 19, the Department of Health has partnered with the University of New Mexico, New Mexico Hepatitis C Alliance, El Centro Family Health and New Mexico AIDS Service to host a series of events and raise awareness about the importance of viral hepatitis prevention and care:

On May 12, El Centro Family Health and Department of Health will host a health fair from 11 to 3 p.m. at the Wal-Mart, 1610 Riverside Drive in Española. Free viral hepatitis testing and vaccinations are available to those who qualify. Educational and treatment information are also available.

On May 19, New Mexico AIDS Services will extend testing hours from 5 to 7 p.m. to provide free hepatitis and HIV screening and hepatitis A and B vaccine at 625 Truman NE in Albuquerque. Eligibility will be determined based on risk assessment. Call 505-938-7100 for more information.

On May 23, Department of Health and the University of New Mexico will host a webinar presentation about the medical aspects of hepatitis C including treatment, surveillance, counseling, testing and harm reduction from 9 to noon. The webinar is open to the public. To register, e-mail Patrick.Stafford@state.nm.us.

On May 29, New Mexico AIDS Services will host a "Smart Steps" class from 1 to 3 p.m. for people infected with hepatitis C.

Posted by Editors at 12:52 PM --- Printer-friendly version

May 01, 2008

Highly Effective Against HCV Genotype 1

When tested on people with Hepatitis C genotype 1, R7128 proved to be an effective addition to combination therapy after just four weeks' time. In addition to its anti-viral effect, polymerase inhibitor R7128 received good marks for safety and minimal side effects.

R7128 is Safe, Effective in Short-Term for Patients With Hepatitis C Virus Genotype 1: Presented at EASL

By Emma Hitt, PhD

www.docguide.com

MILAN, Italy -- April 29, 2008 -- R7128, a potent inhibitor of hepatitis C virus (HCV) polymerase, appears effective and well tolerated at week 4 after initiation of treatment in combination with pegylated interferon alfa-2a (PEG-INF)/ribavirin, according to interim findings of a randomised trial of patients with genotype 1 HCV, researchers reported here at the 43rd Annual Meeting of the European Association for the Study of the Liver (EASL).

John McHutchison, MD, Associate Director, Duke Clinical Research Institute, Durham, North Carolina, described how the study sought to evaluate the efficacy and safety of R7128 at a dose of 500 mg BID (n = 20) and 1500 mg BID (n = 20), compared with placebo (n = 10) at 4 weeks; each arm also received PEG-INF/ribavirin. Patient characteristics were similar among study arms.

R7128 demonstrated a dose-dependent effect on efficacy parameters. Patients in the placebo group had a 2 log10 reduction in HCV RNA, compared with a 3 log10 reduction of in the 500-mg BID arm and a 5 log10 reduction in the 1500-mg BID arm. Rapid viral response was achieved in 10%, 30%, and 95% of patients in the placebo arm, the 500-mg BID, and the 1500-mg BID R7128 arms, respectively. alanine aminotransferase normalisation was achieved in 60%, 80%, and 70% of the 3 arms, respectively.

R7128 was generally well tolerated, with no apparent serious adverse events associated with R7128. The most common mild adverse events with the 1500-mg BID dose included fatigue (40% vs 20% in placebo), chills (35% vs 20% in placebo), and headache (65% vs 40% in placebo). No evidence of additional haematologic adverse events with R7128 was noted. In addition, amylase, bilirubin, blood urea nitrogen, and creatinine measurements were comparable at week 4 among treatment arms, with no evidence of renal toxicity.

Dose reductions and discontinuations were similar among treatment arms. One patient receiving R7128 1500 mg BID discontinued all treatment due to anorexia, diarrhea, and weight loss on study day 24.

"We observed a significant antiviral effect of R7128 in combination with PEG-INF [plus ribavirin] at week 4," Dr. McHutchison concluded. "Approximately 85% of patients receiving R7128 achieved undetectable HCV RNA by week 4."

According to Dr. McHutchison, two additional cohorts will be enrolled in the current 4-week triple combination study: a 1000-mg BID arm in treatment-naive patients with genotype 1 HCV and a 1500-mg BID arm in treatment-experienced patients with genotype 2 or 3 HCV. Both arms will also receive PEG-INF/ribavirin. An international phase 2b study is also underway to evaluate R7128 in triple combination for up to 12 weeks.

Funding for this study was provided by Roche.

[Presentation title: Potent Antiviral Activity of the HCV Nucleoside Polymerase Inhibitor R7128 With PEG-IFN and Ribavirin: Interim Results of R7128 500mg BID for 28 Days. Abstract 66]

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