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Nonresponders to Interferon-based Treatment of HCV Exhibit an Increased Long-Term Hazard of Cirrhosis Compared to Never Treated

The long-term consequences of failed interferon-alpha based hepatitis C treatment on liver morbidity and survival have not been fully explored. We performed retrospective analyses to assess long-term clinical outcomes among treated and untreated patients with hepatitis C virus in two independent cohorts from a United States Veterans Affairs Medical Center and a University Teaching Hospital. Eligible patients underwent liver biopsy during consideration for interferon-alpha based treatment between 1992 and 2007. They were assessed for the probability of developing cirrhosis during follow-up using Cox proportional hazards models, stratified by pretreatment liver fibrosis stage and adjusted for known risk factors for cirrhosis and characteristics affecting treatment selection. The major predictor was a time-dependent covariate for treatment outcome among four patient groups: 1) patients with sustained viral response to treatment; 2) treatment relapsers; 3) treatment nonresponders; and 4) never treated patients. Treatment nonresponders in the Veterans cohort had a statistically significantly increased hazard of cirrhosis (HR = 2.35, CI 1.18-4.69) compared to never treated patients during a mean follow-up period of 10 years. In a replication cohort from the University Hospital, nonresponders also had a significantly increased hazard of cirrhosis (HR = 5.90, CI 1.50-23.24) during a mean follow-up period of 7.7 years. Conclusion: These unexpected findings suggest that hepatic inflammation and fibrosis may be accelerated by interferon-alpha based antiviral therapies in patients who fail to clear the hepatitis C virus.