Incidence of Hepatocellular Carcinoma and Associated Risk Factors in Hepatitis C-Related Advanced Liver Disease
Received 27 May 2008; accepted 11 September 2008. published online 19 September 2008.
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.
⁎Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, Michigan
‡Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland
§Division of Gastroenterology, University of California-Irvine, Irvine, California, and Gastroenterology Service, VA Long Beach Healthcare System, Long Beach, California
∥Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, Missouri
¶Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, Virginia
#New England Research Institutes, Watertown, Massachusetts
⁎⁎Section of Hepatology, Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, Denver, Colorado
‡‡Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California
§§Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas
∥∥Departments of Medicine and Molecular & Structural Biology and The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, Connecticut
¶¶Gastrointestinal Unit (Medical Services), Massachusetts General Hospital and the Department of Medicine, Harvard Medical School, Boston, Massachusetts
##Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland
⁎⁎⁎Virology Division, Department of Laboratory Medicine, University of Washington, Seattle, Washington, DC
‡‡‡Division of Hepatic Pathology and the Veterans Administration Special Reference Laboratory for Pathology, Armed Forces Institute of Pathology, Washington, DC
Address requests for reprints to: Anna S. Lok, MD, Division of Gastroenterology, University of Michigan Hospitals, 3912 Taubman Center, SPC 5362, Ann Arbor, Michigan 48109. fax: (734) 936-7392
H.L.B.'s current address is Carolinas Medical Center, Charlotte, North Carolina.
The authors disclose the following: Financial relationships of the authors with Hoffmann–La Roche, Inc, are as follows: A. S. Lok is a consultant; T. R. Morgan is a consultant, on the speaker's bureau, and receives research support; A. M. Di Bisceglie is a consultant, on the speaker's bureau, and receives research support; R. K. Sterling is a consultant, on the speaker's bureau, and receives research support; G. T. Everson is a consultant, on the speaker's bureau, and receives research support; K. L. Lindsay is a consultant and receives research support; W. M. Lee receives research support; H. L. Bonkovsky receives research support. Authors with no financial relationships related to this project are L. B. Seeff, T. M. Curto, J. L. Dienstag, M. G. Ghany, C. Morishima, and Z. D. Goodman. Potential investigator conflict of interest was disclosed to study participants.
Supported by the National Institute of Diabetes and Digestive and Kidney Diseases (contract numbers are listed in Appendix 1); the National Institute of Allergy and Infectious Diseases (NIAID); the National Cancer Institute; the National Center for Minority Health and Health Disparities; General Clinical Research Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed in Appendix 1); and by Hoffman–La Roche, Inc, through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health.
This is publication No. 34 from the HALT-C Trial Group.
ABSTRACT
Incidence of Hepatocellular Carcinoma and Associated Risk Factors in Hepatitis C-Related Advanced Liver Disease