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Department of Medicine and Therapeutic, The Chinese University of Hong Kong, Hong Kong, People's Republic of China
We appreciate the interest of Liu and Kao [1] in our work. The relative prevalence of hepatitis B virus (HBV) genotype C subgroups in different parts of Asia is definitely an important topic for future study. Although configurations at nucleotide 1858 of the precore region are not 100% accurate in differentiating the genotype C HBV subgroups, 95% of HBV genotype Cs isolates have a C at 1858 (C1858), and all HBV genotype Ce isolates have a T at 1858 (T1858), according to the results of phylogenetic analysis [2]. We agree that the majority of HBV genotype C isolates in Taiwan belong to genotype Ce, but more study is desirable for confirmation [1].
Basal core promoter (BCP) mutations (A1762T and G1764A) and precore stop-codon mutations (G1896A) are both mechanisms of hepatitis Be antigen (HBeAg) seroconversion [3]. In other words, these mutations probably develop in response to host immune clearance of the virus. HBV with C1858 cannot develop precore stop-codon mutations; therefore, the BCP mutations are selected [4]. On the other hand, HBV with T1858 can develop precore stop-codon mutations for HBeAg seroconversion, and the prevalence of BCP mutations is lower [4]. In Taiwan, most HBV genotype C isolates have T1858; hence, the relative prevalence of BCP mutations may be lower than it is in other Asian countries [1, 5]. It will be interesting to study the relative prevalence of HBV genotypes Cs and Ce among Taiwanese patients with hepatocellular carcinoma (HCC). If C1858 is found to be more prevalent in patients with HCC than in those without HCC, this might explain the higher prevalence of BCP mutations associated with HCC in Taiwan. It would also provide indirect evidence that HBV genotype C subgroups have some bearing on the risk of cancer development. Because previous studies have already suggested that HBV genotype C is more carcinogenic than HBV genotype B [57], this valuable information may further define the risk-stratification strategy of HCC surveillance.
References
1. Liu C-J, Kao J-H. Subgenotypes of hepatitis B virus genotype C in Taiwan . J Infect Dis 2005; 192:13089 (in this issue). First citation in article
2. Chan HLY, Tsui SKW, Tse C-H, et al. Epidemiology and virological characteristics of 2 subgroups of hepatitis B virus genotype C. J Infect Dis 2005; 191:202232. First citation in article
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