Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease

Abstract

Background & 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.

Methods: Hepatitis C virus-positive patients with bridging fibrosis or cirrhosis who 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.

Results: 1,005 patients (mean age, 50.2 years; 71% male; 72% white race) 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%, respectively (P= .78), and was higher among patients with cirrhosis than those with bridging fibrosis, 7.0% vs 4.1%, respectively (P= .08). HCC developed in 8 (17%) patients whose serial biopsy specimens 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.

Conclusions: 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.

Trial registration: ClinicalTrials.gov NCT00006164.

Conflict of interest statement

Potential investigator conflict of interest had been disclosed to study participants

Figures

Figure 1

Kaplan-Meier estimates of cumulative incidence of HCC (A) among patients randomized to maintenance peginterferon treatment or control and (B) among patients with bridging fibrosis (Ishak 3–4) vs. cirrhosis (Ishak 5–6) on baseline biopsy. Cases diagnosed within 12 months of enrollment were presumed to have been present at the time of enrollment and were excluded. One patient in the treatment group met criteria for HCC 11 months after randomization. This patient relapsed after 48 weeks of Lead-in treatment and had been in the study for 16 months at the time of randomization.

Figure 1

Kaplan-Meier estimates of cumulative incidence of HCC (A) among patients randomized to maintenance peginterferon treatment or control and (B) among patients with bridging fibrosis (Ishak 3–4) vs. cirrhosis (Ishak 5–6) on baseline biopsy. Cases diagnosed within 12 months of enrollment were presumed to have been present at the time of enrollment and were excluded. One patient in the treatment group met criteria for HCC 11 months after randomization. This patient relapsed after 48 weeks of Lead-in treatment and had been in the study for 16 months at the time of randomization.

Figure 2

Kaplan-Meier estimates of cumulative incidence of HCC among patients predicted to have low, intermediate, and high risk of HCC according to regression Model IV.

Figure 3

Kaplan-Meier estimates of cumulative incidence of HCC (A) in patients with and without esophageal varices or cirrhosis and (B) in patients with baseline platelet (plt) count 150 × 1000/mm3

Figure 3

Kaplan-Meier estimates of cumulative incidence of HCC (A) in patients with and without esophageal varices or cirrhosis and (B) in patients with baseline platelet (plt) count 150 × 1000/mm3