Initial clinical outcomes occurred more frequently among subjects with cirrhosis (7.5% per year) than subjects with fibrosis (3.3% per year) (P < 0.0001). Child-Turcotte-Pugh (CTP) score ≥7 was the

most common first outcome, followed by hepatocellular carcinoma. Following occurrence of a CTP score ≥7, the rate of subsequent events increased to 12.9% per year, including a death rate of 10% per year. Age and sex did not influence outcome rates. Baseline platelet selleck 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. Conclusion: 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. (HEPATOLOGY 2011) Most published data on the rate of progression of chronic hepatitis C, except after transfusion-associated non-A, non-B hepatitis,1 have been derived from single-center studies, which were often small and lacked protocol-driven

systematic data collection.1-10 Based on such reports, the annual incidence of progression to hepatic decompensation in compensated cirrhosis has been estimated to be ≈6% (range, 4%-8%). In the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial,11, 12 we enrolled 1,050 patients with histologically advanced chronic hepatitis C who had failed to AZD2014 manufacturer achieve a sustained virologic response with peginterferon-ribavirin therapy; subjects were assigned randomly to receive low-dose

peginterferon alfa-2a (90 μg/week) or no further treatment for 3.5 years.11 Because the treated and untreated control groups experienced similar rates of clinical progression,12 the combined HALT-C Trial cohort provided a unique opportunity to determine rates BCKDHA of clinical progression in a large, prospectively followed population with histologically advanced, compensated chronic hepatitis C. Extension of the study beyond the 3.5-year randomized treatment phase for up to 8 years provided the opportunity to characterize prospectively the course of advanced chronic hepatitis C more comprehensively than has been possible heretofore. In this article, we describe the frequency and temporal development of the major clinical outcomes of hepatic decompensation. We also describe the sequential emergence of laboratory changes associated with hepatic dysfunction and their relationship to clinical outcomes. ALT, alanine aminotransferase; CTP, Child-Turcotte-Pugh; HALT-C, Hepatitis C Antiviral Long-term Treatment against Cirrhosis; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; MELD, model of end-stage liver disease. The design of the HALT-C Trial (ClinicalTrials.gov #NCT00006164) and results of this randomized trial of peginterferon maintenance therapy were described.