Distribution and characteristics of hepatitis B virus genotype C subgenotypes in China*

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Abstract
Summary. Genetic diversity within the same hepatitis B virus (HBV) genotype indicates the presence of several subgenotypes. We have found that genotype C is the most common in China, and this study aimed to determine the geographical distribution and characteristics of HBV‐C subgenotypes in the country. A cohort of 534 patients with chronic HBV genotype C infection, collected across China, was analysed by nucleotide sequencing or polymerase chain reaction‐restriction fragment length polymorphism. HBV‐C1/Cs (n = 112, 21%) and HBV‐C2/Ce (n = 397, 74%) were the most common HBV‐C subgenotypes and showed different geographical distribution in China. No significant differences were found between patients infected with HBV‐C1 and HBV‐C2 when comparing liver function tests, hepatitis B e antigen positive rate and clinical manifestations. We identified two other types of HBV‐C provisionally designated as HBV‐CD1 and HBV‐CD2, which have particular virological features and clustered in one geographic area. These two types of C/D hybrids have emerged through recombination with genotype D and encode serotype ayw2 hepatitis B surface antigen. In conclusion, there are at least four subtypes of HBV genotype C: subgenotypes C1, C2 and two types of C/D recombinants CD1 and CD2 in China, which have a distinct geographic distribution. Whether HBV‐C subgenotypes differ in their impact on liver disease progression requires prospective studies.