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, HALT-C Trial Group, Gyongyi Szabo, Barbara F Banner, Maureen Cormier, Donna Giansiracusa, Michelle Kelley, Bruce Bacon, Brent Neuschwander-Tetri, Debra King, Raymond T Chung, Andrea E Reid, Atul K Bhan, Wallis A Molchen, S Russell Nash, Jennifer DeSanto, Carol McKinley, John C Hoefs, John R Craig, M Mazen Jamal, Muhammad Sheikh, Choon Park, Thomas E Rogers, Janel Shelton, Nicole Crowder, Rivka Elbein, Sugantha Govindarajan, Carol B Jones, Susan L Milstein, Robert J Fontana, Joel K Greenson, Pamela A Richtmyer, R Tess Bonham, Mitchell L Shiffman, Melissa J Contos, A Scott Mills, Charlotte Hofmann, Paula Smith, T Jake Liang, David Kleiner, Yoon Park, Elenita Rivera, Vanessa Haynes-Williams, James E Everhart, Elizabeth C Wright, Jay H Hoofnagle, David R Gretch, Minjun Chung Apodaca, Rohit Shankar, Kristin K Snow, Anne M Stoddard, Linda Massey, Deepa Naishadham, Fanny Monge, Michelle Parks, Gary L Davis, Guadalupe Garcia-Tsao, Michael Kutner, Stanley M Lemon, Robert P Perrillo, 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, HALT-C Trial Group, Gyongyi Szabo, Barbara F Banner, Maureen Cormier, Donna Giansiracusa, Michelle Kelley, Bruce Bacon, Brent Neuschwander-Tetri, Debra King, Raymond T Chung, Andrea E Reid, Atul K Bhan, Wallis A Molchen, S Russell Nash, Jennifer DeSanto, Carol McKinley, John C Hoefs, John R Craig, M Mazen Jamal, Muhammad Sheikh, Choon Park, Thomas E Rogers, Janel Shelton, Nicole Crowder, Rivka Elbein, Sugantha Govindarajan, Carol B Jones, Susan L Milstein, Robert J Fontana, Joel K Greenson, Pamela A Richtmyer, R Tess Bonham, Mitchell L Shiffman, Melissa J Contos, A Scott Mills, Charlotte Hofmann, Paula Smith, T Jake Liang, David Kleiner, Yoon Park, Elenita Rivera, Vanessa Haynes-Williams, James E Everhart, Elizabeth C Wright, Jay H Hoofnagle, David R Gretch, Minjun Chung Apodaca, Rohit Shankar, Kristin K Snow, Anne M Stoddard, Linda Massey, Deepa Naishadham, Fanny Monge, Michelle Parks, Gary L Davis, Guadalupe Garcia-Tsao, Michael Kutner, Stanley M Lemon, Robert P Perrillo
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
Source: PubMed