High viral load and hepatitis B virus subgenotype ce are associated with increased risk of hepatocellular carcinoma.
OBJECTIVE
We aimed to investigate the impact of hepatitis B virus (HBV) DNA and HBV genotypes/subgenotypes on the risk of hepatocellular carcinoma (HCC).


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.


CONCLUSIONS
High HBV DNA level and HBV genotype C, particularly subgenotype Ce, increased the risk of HCC in chronic hepatitis B.
Chan
Henry Lik-Yuen
HL
Department of Clinical Oncology, Sir YK Pao Center for Cancer, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
Tse
Chi-Hang
CH
Mo
Frankie
F
Koh
Jane
J
Wong
Vincent Wai-Sun
VW
Wong
Grace Lai-Hung
GL
Lam Chan
Stephen
S
Yeo
Winnie
W
Sung
Joseph Jao-Yiu
JJ
Mok
Tony Shu-Kam
TS
D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D016009:Chi-Square Distribution; D005260:Female; D005838:Genotype; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D018709:Statistics, Nonparametric; D019562:Viral Load