HALT-C Finds High Rate of Liver-Related Death and Transplants among Interferon Non-Responders

Chronic hepatitis C patients in the HALT-C study who did not achieve sustained response to standard combination therapy or long-term pegylated interferon maintenance therapy had a high rate of liver transplantation and liver-related death, researchers reported in the August 2011 issue of Hepatology.

Jules Dienstag and fellow investigators with the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial sought to learn more about disease progression among people with chronic hepatitis C virus (HCV) infection who had histologically advanced but compensated liver disease.

HALT-C was a randomized study of extended (3.5 years) pegylated interferon alfa-2a (Pegasys) monotherapy for patients with advanced fibrosis (Ishak stage 3-6) who did not achieve sustained virological response with a standard course of pegylated/ribavirin combination therapy.

The main study found that long-term interferon did not significantly reduce the risk of adverse outcomes including progression to cirrhosis, liver cancer, decompensation, or death.

In the present analysis, the researchers looked at liver disease progression after stopping therapy. It included 1050 HALT-C participants, 60% with advanced fibrosis and 40% with cirrhosis. Since maintenance treatment did not alter disease progression, the treated and untreated control patients were combined. The investigators assessed the rate of progression to cirrhosis over 4 years and clinical outcomes over 8 years.

Results

• Overall, 679 liver-related adverse clinical outcomes occurred among 329 participants during 8 years of follow-up.
• Among patients with advanced fibrosis, the likelihood of progression to cirrhosis was 9.9% per year.
• First-time clinical outcomes occurred more frequently among people who started with cirrhosis (7.5% per year) than those who started with advanced fibrosis (3.3% per year).
• During 8 years of follow-up, 12.2% of patients with advanced fibrosis and 31.5% of those with cirrhosis underwent liver transplantation or died.
• The most common first-time adverse outcome was Child-Turcotte-Pugh (CTP) score reaching 7 or higher.
• The second most common clinical outcome was hepatocellular carcinoma.
• Among patients whose CTP score rose to 7 or higher, the rate of subsequent adverse outcomes increased to 12.9% per year, including a death rate of 10.0% per year.
• Patient age and sex did not influence outcome rates.
• Baseline platelet count was a strong predictor of all adverse clinical outcomes.

Based on these findings, the researchers concluded, "Among patients with advanced hepatitis C who failed peginterferon and ribavirin therapy, the rate of liver-related outcomes, including death and liver transplantation, is high, especially once the CTP score reaches at least 7."

Investigator affiliations: Gastrointestinal Unit, Massachusetts General Hospital, and Department of Medicine, Harvard Medical School, Boston, MA; Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD; Division of Gastroenterology, University of California-Irvine, Irvine, CA; Gastroenterology Service, VA Long Beach Healthcare System, Long Beach, CA; Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, MO; Department of Medicine, University of Connecticut Health Center, Farmington, CT; Carolinas Medical Center, Charlotte, NC; New England Research Institutes, Watertown, MA; Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD; Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD; Hepatology and Liver Center, Division of Gastroenterology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA; Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, VA; Section of Hepatology, Division of Gastroenterology and Hepatology, University of Colorado Denver, School of Medicine, Aurora, CO; Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA; Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX; Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI; Division of Virology, Department of Laboratory Medicine, University of Washington, Seattle, WA.

9/9/11

Reference

JL Dienstag, MG Ghany, TR Morgan, et al (HALT-C Trial Group). A prospective study of the rate of progression in compensated, histologically advanced chronic hepatitis C. Hepatology 54(2):396-405 (abstract). August 2011.