Digestive Diseases News
Winter 2009

Long-term Peginterferon Therapy for Hepatitis C Treatment Reduces Viral Levels but Liver Damage Continues

Treating patients who have chronic hepatitis C and advanced liver disease with long-term peginterferon significantly decreases liver enzymes, viral levels, and liver inflammation, but treatment does not slow or prevent the progression of serious liver disease, according to a study funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

The study’s findings come from the clinical trial Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) and are reported in the December 4 issue of The New England Journal of Medicine. Additional support for HALT-C comes from Hoffmann-La Roche, Inc.

“The results from HALT-C show without question that maintenance therapy with peginterferon does not prevent progression of liver disease among patients who have failed prior treatments,” said James Everhart, M.D., project scientist for HALT-C in the NIDDK’s Division of Digestive Diseases and Nutrition. “These findings heighten the incentive to develop more effective drugs for patients with severe liver disease due to hepatitis C.”

Peginterferon therapy for up to 48 weeks is standard for chronic hepatitis C. Nonresponders—patients who do not have a sustained response to initial therapy—are given the drug over a longer time, based on studies showing this approach suppresses viral and enzyme levels even if the virus is not completely eliminated. However, it was not known if long-term maintenance therapy would improve important clinical outcomes such as liver damage and death.

HALT-C, a randomized, multicenter trial of 1,050 nonresponders, tested whether long-term treatment with peginterferon alfa-2a (Pegasys) would reduce the development of cirrhosis, liver cancer, or liver failure. The 517 patients randomized to the treatment group received 90 micrograms of peginterferon in weekly injections for 3.5 years. The 533 patients in the control group underwent the same follow-up and care as the treated patients, including liver biopsies, quarterly clinic visits, and blood tests but did not receive peginterferon injections. All patients had advanced liver fibrosis, a gradual scarring of the liver that puts patients at risk for progressive liver disease and liver failure.

The outcomes studied in HALT-C were death, liver cancer, or liver failure and, for those who did not have cirrhosis initially, the development of cirrhosis. At the end of the study, 34.1 percent of the treatment group and 33.8 percent of the control group had experienced at least one outcome. Patients in the treatment group had significantly lower blood levels of the hepatitis C virus and improvement in liver inflammation. However, no major difference existed in rates of any of the primary outcomes between the groups.

Among treated patients, 17 percent stopped peginterferon after 18 months and 30 percent stopped the drug after 2 years. Infections and musculoskeletal or digestive problems were the most common reasons for stopping the drug.

Important Step

Looking into how maintenance therapy works in nonresponders is an important step, according to HALT-C Study Chair and Principal Investigator Adrian M. Di Bisceglie, M.D., professor of internal medicine at Saint Louis University School of Medicine. “Patients should not receive interferon as maintenance therapy for chronic hepatitis C. However, we can build on what was learned in HALT-C to identify better treatments that may delay or prevent liver damage in patients with advanced disease.”

The hepatitis C virus infects more than 100 million people worldwide and as many as 4 million people in the United States. Hepatitis C ranks with alcohol abuse as the most common cause of chronic liver disease and leads to about 1,000 liver transplants in the United States each year. The best current antiviral therapy of peginterferon given by injection in combination with oral ribavirin for about 6 months to a year eliminates the virus in about 50 percent of infected patients.

The NIDDK has fact sheets and easy-to-read booklets about hepatitis C at www.digestive.niddk.nih.gov/ddiseases/pubs/hepatitis/index.htm.

For information about NIDDK liver disease research, see www2.niddk.nih.gov/AboutNIDDK/ResearchAndPlanning/Liver_Disease/Action_Plan_For_Liver_Disease_Intro.htm.

For more information about the HALT-C trial, see www.niddk.nih.gov/patient/halt-c/halt-c.htm.

The following researchers and clinical centers conducted the HALT-C study:

• Jules L. Dienstag, M.D., Massachusetts General Hospital and Harvard Medical School, Boston
• Adrian M. Di Bisceglie, M.D. (study chair), Saint Louis University School of Medicine
• Anna S. Lok, M.D., University of Michigan Medical Center, Ann Arbor
• Gyongyi Szabo, M.D., Ph.D., University of Massachusetts, Worcester
• Timothy R. Morgan, M.D., University of California, Irvine, and VA Long Beach Healthcare System, Long Beach, CA
• Gregory T. Everson, M.D., University of Colorado Health Sciences Center, Denver
• Herbert L. Bonkovsky, M.D., University of Connecticut Health Center, Farmington
• Karen L. Lindsay, M.D., Keck School of Medicine, University of Southern California, Los Angeles
• William M. Lee, M.D., University of Texas Southwestern Medical Center, Dallas
• Mitchell L. Shiffman, M.D., Virginia Commonwealth University Medical Center, Richmond
• Chihiro Morishima, M.D., and David Gretch, M.D., Ph.D., University of Washington, Seattle
• Kristin K. Snow, Sc.D., New England Research Institutes, Watertown, MA
• Marc G. Ghany, M.D., Liver Disease Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD

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NIH Publication No. 09–4552
March 2009