BACKGROUND & AIMS: The incidence of liver disease progression among subjects with histologically advanced but compensated, chronic hepatitis C is incomplete.

METHODS: The Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial was a randomized study of 3.5 years of maintenance peginterferon treatment on liver disease progression among patients who had not cleared virus on peginterferon and ribavirin therapy. Patients were followed subsequently off therapy. Because maintenance peginterferon treatment did not alter liver disease progression, we analyzed treated and control patients together. Among 1,050 subjects (60% advanced fibrosis, 40% cirrhosis), we determined the rate of progression to cirrhosis over 4 years and of clinical outcomes over 8 years.

RESULTS: Among patients with fibrosis, the incidence of cirrhosis was 9.9% per year. 679 clinical outcomes occurred among 329 subjects. Initial clinical outcomes occurred more frequently among subjects with cirrhosis (7.5%/year) than with fibrosis (3.3%/year) (P <0.0001). Child-Turcotte-Pugh (CTP) ≥7 was the most common first outcome, followed by hepatocellular carcinoma. Following occurrence of a score CTP ≥7, the rate of subsequent events increased to 12.9%/year, including a death rate of 10%/year. Age and sex did not influence outcome rates. Baseline platelet count was a strong predictor of all clinical outcomes. During the 8 years of follow-up, death or liver transplantation occurred among 12.2% of patients with advanced fibrosis and 31.5% of those with cirrhosis.

CONCLUSIONS: Among patients with advanced hepatitis C who failed peginterferon and ribavirin, the rate of liver-related outcomes, including death and liver transplantation, is high, especially once CTP reaches at least 7.