title: Death From Liver Disease and Development of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B Virus Infection: A Prospective Study.
abstract: BackgroundPatients with chronic hepatitis B virus (HBV) infection are at risk for death from complications of liver disease and development of hepatocellular carcinoma (HCC). To identify the time course and risk factors associated with these events, we conducted a prospective study in chronic hepatitis B patients referred to our clinic.MethodsFrom January 1989 to March 1998, 400 hepatitis B surface antigen (HBsAg)-positive patients were classified into three categories: inactive carriers (N=110), chronic hepatitis (N=151), and cirrhosis (N=139). These patients were observed at 3- to 6-month intervals with liver tests, alpha-fetoprotein (AFP) levels, and ultrasound examinations. The study endpoints were death from liver disease complications and development of HCC.ResultsThe patients were followed for a mean time (± SD) of 83.6 ± 39.6 months. During this period, no liver-related deaths or HCC were noted in inactive carriers. However, 38 of 139 (27.3%) patients with cirrhosis died from non-HCC-related liver complications. Multivariate analysis demonstrated that male sex (odds ratio [OR] 5.9; 95% confidence interval [CI], 2.0-22.6;P=.003), decreased initial serum albumin (OR 69.1; 95% CI, 11.5-486.4;P=.0009), low platelet count (OR 8.8; 95% CI, 0.96-92.9;P=.05), and presence of cirrhosis (OR 14.2; 95% CI, 3.4-111.8;P=.0009) were independently associated with increased mortality from chronic hepatitis B. During the same time period, nine of 151 (6.0%) chronic hepatitis patients and 22 of 139 (15.8%) patients with cirrhosis developed HCC. By multivariate analysis, progression to HCC was associated with advanced age (OR 19.7; 95% CI, 1.9-231.9;P=.01) and presence of cirrhosis (OR 3.6; 95% CI, 1.6-8.9;P=.003). Patients positive for hepatitis B early antigen (HBeAg) and HBeAg antibodies experienced liver-related deaths and developed HCC at similar rates.ConclusionsThis prospective study from the United States confirms previous observations of the high risk of mortality and development of HCC in patients infected with HBV. To decrease the risk of these complications, antiviral therapy should be initiated early in the course of the disease. In addition, surveillance for HCC must be performed at least every 6 months in patients with chronic hepatitis and cirrhosis.
authors.affiliation: Dr. Tong is Chief at The Liver Center, Huntington Medical Research Institutes, Pasadena, Calif, where Dr. Tyson is a Research Scientist and Mr. Kao is a Research Associate. Dr. Tong is also the Director of Clinical Hepatology and Associate Director, Dumont-UCLA Liver Cancer Center at the Pfleger Liver Institute at the David Geffen School of Medicine at the University of California, Los Angeles. Dr. Blatt is Senior Vice President, Preclinical and Applied Research, at Intermune, Inc., in Brisbane, Calif.
authors.forename: Myron J
authors.initials: MJ
authors.lastname: Tong
authors.affiliation: Dr. Tong is Chief at The Liver Center, Huntington Medical Research Institutes, Pasadena, Calif, where Dr. Tyson is a Research Scientist and Mr. Kao is a Research Associate. Dr. Tong is also the Director of Clinical Hepatology and Associate Director, Dumont-UCLA Liver Cancer Center at the Pfleger Liver Institute at the David Geffen School of Medicine at the University of California, Los Angeles. Dr. Blatt is Senior Vice President, Preclinical and Applied Research, at Intermune, Inc., in Brisbane, Calif.
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Blatt
authors.affiliation: Dr. Tong is Chief at The Liver Center, Huntington Medical Research Institutes, Pasadena, Calif, where Dr. Tyson is a Research Scientist and Mr. Kao is a Research Associate. Dr. Tong is also the Director of Clinical Hepatology and Associate Director, Dumont-UCLA Liver Cancer Center at the Pfleger Liver Institute at the David Geffen School of Medicine at the University of California, Los Angeles. Dr. Blatt is Senior Vice President, Preclinical and Applied Research, at Intermune, Inc., in Brisbane, Calif.
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Tyson
authors.affiliation: Dr. Tong is Chief at The Liver Center, Huntington Medical Research Institutes, Pasadena, Calif, where Dr. Tyson is a Research Scientist and Mr. Kao is a Research Associate. Dr. Tong is also the Director of Clinical Hepatology and Associate Director, Dumont-UCLA Liver Cancer Center at the Pfleger Liver Institute at the David Geffen School of Medicine at the University of California, Los Angeles. Dr. Blatt is Senior Vice President, Preclinical and Applied Research, at Intermune, Inc., in Brisbane, Calif.
authors.forename: Vincent W C
authors.initials: VW
authors.lastname: Kao
keywords: Hepatitis B; chronic hepatitis; cirrhosis; hepatocellular carcinoma; inactive carriers; natural history