Could statins be a new option for hepatitis C patients?

WASHINGTON, D.C. (May 20, 2007) -- Research presented today at Digestive Disease Week® 2007 (DDW®) demonstrates the potential of statins, important cholesterol management therapies, for improving the management of hepatitis C — a disease that affects nearly four million Americans. Although there have been no new treatments for hepatitis C since the introduction of pegylated interferon in 2001, the opportunity to develop a new generation of therapies that offer better outcomes may be imminent. DDW is the largest international gathering of physicians and researchers in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.

"Studies such as these are designed to improve the effectiveness of antivirals – the standard of care therapy for hepatitis C," said John Vierling, M.D., Baylor College of Medicine. "The findings from these studies support the rationale and need for larger, controlled trials that may provide additional and more advantageous hepatitis C treatment options."

Researchers have yet to report on the concept that hepatitis C virus (HCV) patients who take statins may experience improvements in alanine transaminase (ALT, liver enzymes) levels. Use of statins for hepatitis C has not occurred in the past as the FDA-approved package insert for every statin lists "active liver disease" as a contraindication for use and hepatitis C would certainly qualify as an active liver disease. In such a setting, a researcher must request a special license form from the FDA called an investigational new drug (IND) license. As part of an IRB and FDA-approved 14-day study looking at the antiviral effect of fluvastatin (FLV) in vivo, researchers reported the total bilirubin (TB, yellow breakdown product) and ALT results and compared the findings to an existing hepatitis C registry data.

Initial results showed that three patients with abnormal ALTs at baseline experienced significant improvement and nine patients who started with normal ALTs stayed normal. In addition, there were no significant changes in TB levels. No liver problems were noted despite FLV doses that were up to four times the highest FDA-approved dose.

Experts also examined the existing HCV registry and noted both the number of patients who improved their abnormal ALT levels after statin therapy and the number of patients who maintained their normal ALT levels after initiation of statin therapy. Of the abnormal ALT group (13 of 60 pts), 12 had improved ALT and one stayed unchanged. Of the 47 beginning in the normal range, 45 maintained their ALTs. The remaining two who developed a mildly abnormal ALT after beginning a statin were noted as suffering from heavy alcohol abuse, suggesting an unrelated cause for the change.

"This is the first report of prospectively using fluvastatin in HCV patients," says Ted Bader, M.D., of University of Oklahoma in Oklahoma City, Okla., and lead author of this study. "Two remarkable observations were made and data not only supports the lack of harm in this situation, but also seems to suggest a possible salutary effect that needs further study."

Dr. Bader will present this study on Monday, May 21, at 8:30 a.m. in Hall E.

Researchers retrospectively analyzed the effect of taking peginterferon and ribavirin (PI+R, hepatitis C treatment options) and PI+R plus a statin to measure the sustained viral response (SVR, negative virus in blood six months after the end of treatment) rate in hepatitis C patients. A modified intent to treat approach was taken to compare the therapy alone to the therapy with addition of a statin.

In this study, 104 patients taking PI+R were compared to 30 patients who took PI+R plus a statin. Almost all patients (25 of the 30) taking a statin were on simvastatin, two were on lovastatin, two were on atorvastatin and one on fluvastatin. According to study results, the patients on standard treatment achieved a 37 percent SVR rate – the highest SVR reported to date in the medical literature for a VA-based population. Having a high SVR rate means a cure is 95 percent of the time based upon long-term follow up that is greater than six months after treatment. The SVR rate for patients taking triple therapy, PI+R plus a statin, was 63 percent.

Statins appear to be associated with a higher SVR rate when added to standard PI+R therapy. Retrospective data are subject to many problems and inaccuracies and should be only used to plan prospective trials.

"It is important for statins to be studied prospectively for their effect on hepatitis C," says Ted Bader, M.D., of University of Oklahoma in Oklahoma City, Okla., and lead author of this study. "Further study may contribute to developing a more effective outcome of treatment."

Dr. Bader will present this study on Monday, May 21, at 8:30 a.m. in Hall E.

Digestive Disease Week® (DDW®) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW takes place May 19-24, 2007 in Washington, D.C. The meeting showcases more than 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology.