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MAINTENANCE THERAPY FOUND INEFFECTIVE HALT-C STUDY
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Prolonged Antiviral Therapy With Peginterferon to Prevent Complications of Advanced Liver Disease Associated With Hepatitis C: Results of the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial
This is the program abstract.
Reported by Jules Levin, NATAP
AASLD, Nov 2-6, 2007, Boston, MA
A. M. Di Bisceglie1; M. L. Shiffman2; G. T. Everson3; K. L. Lindsay4; J. E. Everhart5; E. C. Wright6; W. M. Lee7; A. S. Lok8; H. Bonkovsky9; T. R. Morgan10; J. L. Dienstag11; M. Ghany12; C. Morishima13; K. K. Snow14
1. Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, MO, USA.
2. Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, VA, USA.
3. Section of Hepatology, Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, Denver, CO, USA.
4. Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
5. Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
6. Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
7. Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA.
8. Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, MI, USA.
9. Departments of Medicine and Molecular & Structural Biology and The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, CT, USA.
10. Division of Gastroenterology and Gastroenterology Service, University of California - Irvine and VA Long Beach Healthcare System, Irvine, CA, USA.
11. Gastrointestinal Unit (Medical Services) and the Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
12. Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
13. Virology Division, Department of Laboratory Medicine, University of Washington, Seattle, WA, USA.
14. New England Research Institutes, Watertown, MA, USA.
Background: Chronic hepatitis C may lead to progressive liver disease with cirrhosis, liver failure, hepatocellular carcinoma (HCC) and death. Not all pts treated with peginterferon and ribavirin achieve a sustained virologic response (SVR); whether long-term antiviral therapy can prevent progressive liver disease in those who do not achieve SVR remains uncertain.
Aims: To determine if long-term maintenance therapy with peginterferon prevents progressive liver disease resulting from hepatitis C.
Methods: We conducted a randomized controlled trial of peginterferon alfa-2a (90 mcg per week) for 3.5 years vs. no treatment in pts with chronic hepatitis C and advanced fibrosis who were nonresponders to prior therapy with peginterferon and ribavirin. Subjects eligible for enrollment had chronic hepatitis C with an Ishak fibrosis score of ≥3 on liver biopsy, a Child-Turcotte-Pugh (CTP) score of ≦6, no history of ascites, encephalopathy or bleeding varices, and no other identifiable cause of liver disease. Participants were stratified according to their stage of fibrosis - Ishak stage 3 or 4 (622 with fibrosis) vs. 5 or 6 (428 with cirrhosis). Pts were seen at 3 month intervals, underwent liver biopsy at 1.5 and 3.5 years after randomization, and were monitored for the following outcomes: death, HCC, hepatic decompensation (variceal hemorrhage, ascites, spontaneous bacterial peritonitis, encephalopathy or a CTP score of ≥7), and, for those with pre-cirrhotic fibrosis at baseline, an increase in fibrosis score of ≥2 points.
Results: 1050 pts were randomized (517 treatment, 533 control). By the end of the study, 34.1% of the treatment and 33.8% of the control group had experienced an outcome (hazard ratio=1.01; 95% CI=0.81-1.26; p=0.91). Although mean serum ALT and HCV RNA levels decreased significantly with treatment (both p<0.0001), as did necroinflammatory changes on liver biopsy (p<0.0001), no significant difference was observed in rates of any of the primary outcomes between groups (Table). The rate of serious adverse events was similar in both groups (284 events among 175 treated and 283 events among 155 control pts). Among treated pts, 17% stopped peginterferon by year 1.5 and 30% by year 3.5.
Summary and Conclusions: Long-term therapy with peginterferon did not reduce the rate of disease progression. These findings do not support maintenance therapy with peginterferon in patients with chronic hepatitis C and advanced hepatic fibrosis who are nonresponders to a course of peginterferon/ribavirin therapy.
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