LIVER

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

H L-Y Chan, A Y Hui, M L Wong, A M-L Tse, L C-T Hung, V W-S Wong, J J-Y Sung

Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong SAR, China

Correspondence to:
Correspondence to:
Dr H L-Y Chan
Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30–32 Ngan Shing St, Shatin, Hong Kong, China; hlychan{at}cuhk.edu.hk

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 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.

Abbreviations: ALT, alanine aminotransferase; anti-HBe, antibody to hepatitis B e antigen; BCP, basal core promoter; HBeAg, hepatitis B e antigen; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; PCR, polymerase chain reaction

Keywords: hepatitis B; genotype; hepatocellular carcinoma; liver cirrhosis; basal core promoter mutations

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