Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease.
OBJECTIVE
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.
Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA. aslok@umich.edu
Anna S
AS
Lok
Leonard B
LB
Seeff
Timothy R
TR
Morgan
Adrian M
AM
di Bisceglie
Richard K
RK
Sterling
Teresa M
TM
Curto
Gregory T
GT
Everson
Karen L
KL
Lindsay
William M
WM
Lee
Herbert L
HL
Bonkovsky
Jules L
JL
Dienstag
Marc G
MG
Ghany
Chihiro
C
Morishima
Zachary D
ZD
Goodman
D000328:Adult; D001706:Biopsy; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D006526:Hepatitis C / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D015994:Incidence; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000150:complications*; D008113:Liver Neoplasms / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins; D012307:Risk Factors
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a