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High Viral Load and Hepatitis B Virus Subgenotype Ce Are Associated With Increased Risk of Hepatocellular Carcinoma

Henry Lik-Yuen Chan, Chi-Hang Tse, Frankie Mo, Jane Koh, Vincent Wai-Sun Wong, Grace Lai-Hung Wong, Stephen Lam Chan, Winnie Yeo, Joseph Jao-Yiu Sung, Tony Shu-Kam Mok

From the Department of Medicine and Therapeutics, Institute of Digestive Disease; and the Department of Clinical Oncology, The Chinese University of Hong Kong, Shatin, Hong Kong

Corresponding author: Tony S.-K. Mok, MD, Department of Clinical Oncology, Sir YK Pao Center for Cancer, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong; e-mail: tony{at}clo.cuhk.edu.hk or mok206551{at}cuhk.edu.hk

Purpose We aimed to investigate the impact of hepatitis B virus (HBV) DNA and HBV genotypes/subgenotypes on the risk of hepatocellular carcinoma (HCC).

Patients and Methods A prospective cohort of patients infected with chronic HBV in a surveillance program for HCC since 1997 was studied. Ultrasound and alpha-fetoprotein evaluation were regularly performed to detect HCC. Risk factors for HCC and the relationship between HBV DNA and HBV genotypes were determined.

Results Among 1,006 patients with a median follow-up of 7.7 years, 86 patients (8.5%) developed HCC. With reference to the low HBV DNA stratum (log HBV DNA 4.5 copies/mL), the hazard ratio for HCC of the intermediate HBV DNA stratum (log HBV DNA > 4.5 to 6.5 copies/mL) was 1.62 (95% CI, 1.05 to 2.48; P = .027) and that of the high HBV DNA stratum (log HBV DNA > 6.5 copies/mL) was 2.73 (95% CI, 1.76 to 4.25; P < .001). Among patients with genotyping results, 330 patients had HBV genotype B and 439 patients had HBV genotype C (94 subgenotype Ce and 345 subgenotype Cs). With reference to HBV genotype B, HBV subgenotype Ce has the highest risk of HCC (hazard ratio = 2.75; 95% CI, 1.66 to 4.56; P < .0001) and HBV subgenotype Cs has intermediate risk (hazard ratio = 1.70; 95% CI, 1.09 to 2.64; P = .020). On multivariate analysis, HBV DNA, HBV genotypes, liver cirrhosis, male sex, older age, and lower serum albumin were independent risk factors of HCC.

Conclusion High HBV DNA level and HBV genotype C, particularly subgenotype Ce, increased the risk of HCC in chronic hepatitis B.

Supported by Michael Kadoorie Cancer Genetics Research Programme and Research Fund for the Control of Infectious Diseases (RFCID; application number 06060122; H.L.-Y.C); and Hong Kong Cancer Fund.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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