Haak-Cheoul Kim

Distribution of hepatitis B virus genotypes in Korea

BACKGROUND/AIMS Considering the incidence of prevailing hepatitis B virus (HBV) genotypes in neighboring nations, the predominance of genotype C in Korea is exceptional and needs to be confirmed by nationwide investigation. METHODS A total of 510 HBsAg (+) or HBeAg (+) serum samples was collected from subjects in several cities and harbors throughout the Korean peninsula for genotype (A-G)-specific multiplex PCR analysis. Another 40 serum samples from chronic HBV carriers from Iksan city were selected for sequencing of the entire HBV genome. Phylogenetic analysis was performed with 22 whole genomic sequences of Korean HBV strains enrolled in GenBank. RESULTS An amplicon was found in 377 specimens and genotype C occupied 98.1% (370 cases); none of the other genotypes were found. A mixed pattern of genotypes B and C was seen in seven specimens (1.9%), of which five were tested using PCR targeting the X fragment; no genotype B bands were found. With the exception of 1 case, which was subgenotype A2, whole sequences of Korean HBV strains (n=62) belonged to subgenotype C2. CONCLUSIONS The prevailing HBV genotype in Korea is C2; the other genotypes occur only rarely. Future studies should include confirmation of the detection of genotypes other than C.

Nucleotide changes related to hepatocellular carcinoma in the enhancer 1/x-promoter of hepatitis B virus subgenotype C2 in cirrhotic patients

Hepatocellular carcinoma (HCC) is widely known to develop more frequently in cirrhotic patients with a high expression of Hepatitis B virus X protein (HBx), which is controlled by the enhancer 1 (Enh1)/X‐promoter. To examine the effect of the mutations in the Enh1/X‐promoter region in hepatitis B virus (HBV) genomes on the development of HCC, we investigated the differences in HBV isolated from cirrhotic patients with or without HCC along with the promoter activities of certain specific mutations within the Enh1/X‐promoter. We examined 160 hepatitis B surface antigen (HBsAg)‐positive cirrhotic patients (80 HCC patients, 80 non‐HCC patients) by evaluating the biochemical, virological, and molecular characteristics. We evaluated the functional differences in certain specific mutations within the Enh1/X‐promoter. The isolated sequences included all of the subgenotypes C2. The sites that showed higher mutation rates in the HCC group were G1053A and G1229A, which were found to be independent risk factors through multiple logistic analysis (P < 0.05). Their promoter activities were elevated 2.38‐ and 4.68‐fold, respectively, over that of the wild type in the HepG2 cells. Similarly, both the mRNA and protein levels of HBx in these two mutants were much higher than that in wild type‐transfected HepG2 cells. Mutated nucleotides of the Enh1/X‐promoter, especially G1053A and G1229A mutations in the HBV subgenotype C2 of patients with cirrhosis, can be risk factors for hepatocarcinogenesis, and this might be due to an increase in the HBx levels through the transactivation of the Enh1/X‐promoter. (Cancer Sci 2010)