Novel subtypes (subgenotypes) of hepatitis B virus genotypes B and C among chronic liver disease patients in the Philippines

Several hepatitis B virus (HBV) subtypes (subgenotypes), HBV/Aa (A1 : Asia/Africa), Ae (A2 : Europe), Ba (B1 : Japan) and Ba (B2 : Asia), have been reported with respect to clinical differences between patients infected with these subtypes (subgenotypes). HBV genotype distribution among patients with chronic liver diseases was investigated in the Philippines, where such studies have not been carried out previously. One hundred sera were obtained from such patients, consisting of 32 chronic hepatitis (CH), 37 cirrhosis and 31 hepatocellular carcinoma (HCC) patients. Nine complete genomes and 100 core promoter/precore genes of HBV were sequenced directly. Phylogenetic analyses revealed 51 HBV/A (Aa/Al), 22 HBV/B and 27 HBV/C strains. Interestingly, most HBV/C strains in the Philippines formed a specific cluster distinct from previous HBV/C strains (Cl-4), indicating a novel subtype (subgenotype), HBV/C5. Moreover, most HBV/B strains fell within the specific cluster of the HBV/B subtype (subgenotype) 135, with viral characteristics of HBV/Ba (132) carrying a recombination with HBV/C over the precore and core genes. Of the three genotypes, HBV/B and HBV/C were significantly more prevalent than HBV/A in cirrhosis and HCC patients (P < 0.02). The prevalence of the core promoter mutations T1 762/Al 764 was higher in HCC patients with HBV/B and HBV/C. Multivariate analysis indicated that age [odds ratio (OR) 3 center dot 43; 95 % confidence interval (Cl) 1 center dot 04-11 center dot 36; P=0-044] and the core promoter mutation (OR 14 center dot 08; 95% Cl 3 center dot 62-4 center dot 74; P < 0 center dot 001) were significant factors for HCC development. In conclusion, novel HBV subtypes (subgenotypes) C5 and 135 are prevalent in the Philippines, as well as HBV/Aa (A1).