Incidence of Hepatocellular Carcinoma and Associated Risk Factors in Hepatitis C-Related Advanced Liver Disease

Anna S. Lok, Leonard B. Seeff, Timothy R. Morgan, Adrian M. di Bisceglie, Richard K. Sterling, Teresa M. Curto, Gregory T. Everson, Karen L. Lindsay, William M. Lee, Herbert L. Bonkovsky, Jules L. Dienstag, Marc G. Ghany, Chihiro Morishima, Zachary D. Goodman

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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.

Original languageEnglish (US)
Pages (from-to)138-148
Number of pages11
JournalGastroenterology
Volume136
Issue number1
DOIs
StatePublished - Jan 2009

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Hepatitis C
Liver Diseases
Hepatocellular Carcinoma
Fibrosis
Incidence
Antiviral Agents
Maintenance
Esophageal and Gastric Varices
Ribavirin
Kaplan-Meier Estimate
Chronic Hepatitis C
Platelet Count
Hepacivirus
Alkaline Phosphatase
Therapeutics
Multivariate Analysis
Smoking
Prospective Studies
Biopsy

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Lok, A. S., Seeff, L. B., Morgan, T. R., di Bisceglie, A. M., Sterling, R. K., Curto, T. M., ... Goodman, Z. D. (2009). Incidence of Hepatocellular Carcinoma and Associated Risk Factors in Hepatitis C-Related Advanced Liver Disease. Gastroenterology, 136(1), 138-148. https://doi.org/10.1053/j.gastro.2008.09.014

Incidence of Hepatocellular Carcinoma and Associated Risk Factors in Hepatitis C-Related Advanced Liver Disease. / Lok, Anna S.; Seeff, Leonard B.; Morgan, Timothy R.; di Bisceglie, Adrian M.; Sterling, Richard K.; Curto, Teresa M.; Everson, Gregory T.; Lindsay, Karen L.; Lee, William M.; Bonkovsky, Herbert L.; Dienstag, Jules L.; Ghany, Marc G.; Morishima, Chihiro; Goodman, Zachary D.

In: Gastroenterology, Vol. 136, No. 1, 01.2009, p. 138-148.

Research output: Contribution to journalArticle

Lok, AS, Seeff, LB, Morgan, TR, di Bisceglie, AM, Sterling, RK, Curto, TM, Everson, GT, Lindsay, KL, Lee, WM, Bonkovsky, HL, Dienstag, JL, Ghany, MG, Morishima, C & Goodman, ZD 2009, 'Incidence of Hepatocellular Carcinoma and Associated Risk Factors in Hepatitis C-Related Advanced Liver Disease', Gastroenterology, vol. 136, no. 1, pp. 138-148. https://doi.org/10.1053/j.gastro.2008.09.014
Lok, Anna S. ; Seeff, Leonard B. ; Morgan, Timothy R. ; di Bisceglie, Adrian M. ; Sterling, Richard K. ; Curto, Teresa M. ; Everson, Gregory T. ; Lindsay, Karen L. ; Lee, William M. ; Bonkovsky, Herbert L. ; Dienstag, Jules L. ; Ghany, Marc G. ; Morishima, Chihiro ; Goodman, Zachary D. / Incidence of Hepatocellular Carcinoma and Associated Risk Factors in Hepatitis C-Related Advanced Liver Disease. In: Gastroenterology. 2009 ; Vol. 136, No. 1. pp. 138-148.
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AU - Lok, Anna S.

AU - Seeff, Leonard B.

AU - Morgan, Timothy R.

AU - di Bisceglie, Adrian M.

AU - Sterling, Richard K.

AU - Curto, Teresa M.

AU - Everson, Gregory T.

AU - Lindsay, Karen L.

AU - Lee, William M.

AU - Bonkovsky, Herbert L.

AU - Dienstag, Jules L.

AU - Ghany, Marc G.

AU - Morishima, Chihiro

AU - Goodman, Zachary D.

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N2 - 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.

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