Genotype C hepatitis B virus infection is associated with an increased risk of hepatocellular carcinoma

• Published in: Gut Vol. 53; no. 10; pp. 1494 - 1498
• Main Authors: Chan, H L-Y, Hui, A Y, Wong, M L, Tse, A M-L, Hung, L C-T, Wong, V W-S, Sung, J J-Y
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Society of Gastroenterology 01-10-2004; BMJ; BMJ Publishing Group LTD; Copyright 2004 by Gut
• Subjects: Abdomen; Adolescent; Adult; Age; Aged; Aged, 80 and over; alanine aminotransferase; ALT; anti-HBe; antibody to hepatitis B e antigen; Antigens; basal core promoter; basal core promoter mutations; BCP; Biological and medical sciences; Carcinoma, Hepatocellular - virology; Child; Deoxyribonucleic acid; DNA; Enzymes; Female; Follow-Up Studies; Gastroenterology. Liver. Pancreas. Abdomen; Genotype; Genotype & phenotype; HBeAg; HBV; HCC; Hepatitis; hepatitis B; hepatitis B e antigen; Hepatitis B virus; Hepatitis B virus - classification; Hepatitis B virus - genetics; Hepatitis B virus - pathogenicity; Hepatitis B, Chronic - complications; Hepatitis B, Chronic - virology; hepatocellular carcinoma; Human viral diseases; Humans; Infectious diseases; Liver; Liver cancer; Liver cirrhosis; Liver Cirrhosis - complications; Liver Neoplasms - virology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical prognosis; Medical sciences; Middle Aged; Mortality; Multivariate analysis; Mutation; Patients; PCR; polymerase chain reaction; Prospective Studies; Risk Factors; Studies; Surveillance; Tomography; Tumors; Ultrasonic imaging; Viral diseases; Viral diseases of the digestive system; Viral hepatitis; Southeast Asia; Taiwan; Splenic disease; Orthohepadnavirus; Hepatic disease; Hepatocellular carcinoma; Risk; Hemopathy; Identification; Epidemiology; Viral hepatitis B; Hepadnaviridae; Diagnosis; Hepatitis B virus; Viral hepatitis C; Human; Nervous system diseases; Typing; Effusion; Genotype; Histology; Malignant tumor; Method; α-Fetoprotein; Cerebral disorder; Infection; Virus; Cirrhosis; Surveillance; Abdominal disease; Viral disease; Hypersplenism; Central nervous system disease; Risk factor; Digestive diseases
• ISSN: 0017-5749; 1468-3288; 1458-3288
• DOI: 10.1136/gut.2003.033324

Background: Identification of risk factors for the development of hepatocellular carcinoma (HCC) is important for HCC surveillance in chronic hepatitis B virus (HBV) infection. Our aim was to study the independent risk factors and effect of HBV genotypes on HCC development in a prospective longitudinal cohort of chronic hepatitis B patients. Patients and methods: Chronic hepatitis B patients recruited since 1997 were prospectively followed up for the development of HCC. HCC was diagnosed by a combination of α fetoprotein, imaging, and histology. Liver cirrhosis was defined as ultrasonic features of cirrhosis together with hypersplenism, ascites, varices, and/or encephalopathy. Results: In total, 426 patients were followed up for 1664 person years; median 225 (range 12–295) weeks. Forty nine (11%) patients had underlying clinical liver cirrhosis. A total of 242 (57%) and 179 (42%) patients had HBV genotypes C and B, respectively. Twenty five patients developed HCC in a median follow up of 121 (range 14–236) weeks. The overall incidence of HCC was 1502 cases per 100 000 person years. On multivariate analysis, clinical liver cirrhosis and HBV genotype C infection were independently associated with HCC development, with an adjusted relative risk of 10.24 (95% confidence interval (CI) 4.39–23.89; p<0.001) and 2.84 (95% CI 1.05–7.72; p = 0.040), respectively. Patient age, sex, hepatitis B e antigen (HBeAg) status, alanine aminotransferase (ALT) levels, and basal core promoter mutations did not predict HCC development. Patients infected with HBV genotype C tended to have persistently positive HBeAg or fluctuating HBeAg status and higher ALT levels during the follow up period. Conclusion: Genotype C HBV infection is an independent risk factor for HCC development in addition to liver cirrhosis.