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

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Journal of Clinical Oncology, Vol 26, No 2 (January 10), 2008: pp. 177-182

High Viral Load and Hepatitis B Virus Subgenotype Ce Are Associated With

Increased Risk of Hepatocellular Carcinoma

Henry Lik-Yuen Chan, Chi-Hang Tse, ie Mo, Jane Koh, Wai-Sun Wong,

Grace Lai-Hung Wong, Lam Chan, Winnie Yeo, ph 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@... or

mok206551@...

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 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.

http://jco.ascopubs.org/cgi/content/abstract/26/2/177

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