Risk for hepatocellular carcinoma with respect to hepatitis B virus genotypes B/C, specific mutations of enhancer II/core promoter/precore regions and HBV DNA levels.
OBJECTIVE
To examine the risks for hepatocellular carcinoma (HCC) with respect to hepatitis B virus (HBV) genotypes, specific viral mutations (MT), serum HBV DNA levels, and cirrhosis.


METHODS
HBV genotypes, 1653/1753/core promoter (CP)/precore MT and HBV DNA levels were determined in 248 HBV patients with HCC and 248 HBV controls.


RESULTS
Genotype C, CP-MT, T1653, HBV DNA levels >or=4 log(10) copies/ml and cirrhosis had a higher risk for HCC compared to patients with genotype B (p = 0.001, OR 1.9), CP wild-type (WT) (p<0.001, OR 4.1), C1653 (p = 0.028, OR 2.4), HBV DNA <4 log(10) copies/ml (p = 0.003, OR 2.1) and without cirrhosis (p<0.001, OR 4.0) respectively. Multivariate analysis showed that CP-MT, T1653, HBV DNA >or=4 log(10) copies/ml and cirrhosis were independent factors for HCC (all p<0.05). A receiver operating characteristics curve showed no cut-off HBV DNA level associated with minimal chance of HCC. Patients with CP-MT and cirrhosis had a 22.2-fold increased risk of HCC compared to patients with CP-WT and without cirrhosis. Patients with CP-MT and HBV DNA levels >or=4 log(10) copies/ml had a 7.2-fold increased risk of HCC compared to patients with CP-WT and HBV DNA levels <4 log(10) copies/ml. Patients with CP-MT and T1653 had a 9.9-fold increased risk of HCC compared to patients with wild-type for both regions.


CONCLUSIONS
CP-MT, T1653, HBV DNA levels >or=4 log(10) copies/ml and cirrhosis are independent factors for development of HCC. The risks increased substantially in patients having these factors in combination.
Yuen
M-F
MF
Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong. mfyuen@hkucc.hku.hk
Tanaka
Y
Y
Shinkai
N
N
Poon
R T
RT
But
D Yiu-Kuen
DY
Fong
D Y-T
DY
Fung
J
J
Wong
D Ka-Ho
DK
Yuen
J Chi-Hang
JC
Mizokami
M
M
Lai
C-L
CL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D016022:Case-Control Studies; D004279:DNA, Viral / Q000097:blood; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005260:Female; D005838:Genotype; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012372:ROC Curve
D004279:DNA, Viral