Document Type



Medicine and Health Sciences


Background and Aims

Although the incidence of hepatocellular carcinoma (HCC) is increasing in the United States, data from large prospective studies are limited. We evaluated the hepatitis C antiviral long-term treatment against cirrhosis (HALT-C) cohort for the incidence of HCC and associated risk factors.


HCV-positive patients with bridging fibrosis or cirrhosis that did not respond to peginterferon and ribavirin were randomized to groups that were given maintenance peginterferon for 3.5 years or no treatment. HCC incidence was determined by Kaplan-Meier analysis and baseline factors associated with HCC were analyzed by Cox regression.


1,005 patients (mean age 50.2 years, 71% male, 72% white) were studied; 59% had bridging fibrosis and 41% had cirrhosis. During a median follow-up of 4.6 years (maximum 6.7 years), HCC developed in 48 patients (4.8%). The cumulative 5-year HCC incidence was similar for peginterferon-treated patients and controls, 5.4% vs. 5.0% (p=0.78), and was higher among patients with cirrhosis than those with bridging fibrosis, 7.0% vs. 4.1% (p=0.08). HCC developed in eight (17%) patients whose serial biopsies showed only fibrosis. A multivariate analysis model comprising older age, black race, lower platelet count, higher alkaline phosphatase, esophageal varices, and smoking was developed to predict the risk of HCC.


We found that maintenance peginterferon did not reduce the incidence of HCC in the HALT-C cohort. Baseline clinical and laboratory features predicted risk for HCC. Additional studies are required to confirm our finding of HCC in patients with chronic hepatitis C and bridging fibrosis.


Gastroenterology. Author manuscript; available in PMC 2013 August 22. Published in final edited form as: Gastroenterology. 2009 January; 136(1): 138–148. Published online 2008 September 18. doi: 10.1053/j.gastro.2008.09.014 PMCID: PMC3749922 NIHMSID: NIHMS502598