ORIGINAL ARTICLE A nationwide molecular epidemiological study on hepatitis B virus in Indonesia: identification of two novel subgenotypes, B8 and C7 Mulyanto Æ Sulaiman Ngongu Depamede Æ Kiely Surayah Æ Fumio Tsuda Æ Koji Ichiyama Æ Masaharu Takahashi Æ Hiroaki Okamoto Received: 7 April 2009 / Accepted: 19 May 2009 Ó Springer-Verlag 2009 Abstract Upon phylogenetic analysis of a partial S gene sequence [396 nucleotides (nt)], 928 hepatitis B virus (HBV) strains obtained from 899 viremic subjects in 28 major cities on 15 islands of Indonesia in 1989–2007 segregated into four HBV genotypes. Genotype B was predominant (66%), followed by genotype C (26%), genotype D (7%), and genotype A (0.8%). Comparative and phylogenetic analyses of the 396-nt S gene sequence of 928 HBV isolates and whole genomic sequences of 25 selected HBV isolates revealed a total of 14 subgenotypes within genotypes A–D: two (A1 and A2) in genotype A (HBV/A), five (B2, B3, B5, B7, and a novel subgenotype, tentatively designated B8) in HBV/B, five (C1, C2, C5, C6, and another novel subgenotype, C7) in HBV/C, and two (D1 and D3) in HBV/D. The distribution of HBV geno- types/subgenotypes, including B8 and C7, seems to be associated with ethnological origins in Indonesia. Introduction Hepatitis B is a major worldwide health problem, with over 350 million chronically infected individuals, some of whom develop severe liver disease including cirrhosis and hepatocellular carcinoma. The prevalence of hepatitis B virus (HBV) infection is generally high in Asia and Africa [17]. Indonesia has a moderate to high endemicity of HBV infection. The carrier rates among apparently healthy populations in Indonesia have been reported to range from 4.0 to 20.3% [13]. Its prevalence varies by island; in gen- eral, areas outside of Java Island have a higher prevalence of hepatitis B surface antigen (HBsAg) (9.2%) than areas within Java (5.0%) [22]. Eight genotypes of HBV, designated A to H, have been identified worldwide [2, 3, 24, 29, 36]. The genotypes B and C (HBV/B and HBV/C, respectively) are predominant in Asia [14, 32, 34, 37]. Subgenotypes have been identified within certain HBV genotypes, i.e., A1–A4 in HBV/A, B1– B7 in HBV/B, C1–C6 in HBV/C, and D1–D6 in HBV/D, with distinct geographical clustering [15, 19, 25, 26, 33]. An earlier classification system divided HBsAg into four major serological subtypes, adw, adr, ayw, and ayr [4, 16]. There is a correlation between HBsAg subtypes and HBV genotypes. In general, infected individuals with HBV genotype of A, B, F, G, or H have subtype adw; those with HBV/C have adr; and those with HBV/D and HBV/E have ayw [14]. The nucleotide sequence data reported in this study have been assigned DDBJ/EMBL/GenBank accession numbers AP011084– AP011108 for 25 entire HBV genomes and AB466339–AB467266 for 928 partial HBV sequences. Mulyanto Á S. N. Depamede Immunobiology Laboratory, Faculty of Medicine, University of Mataram, Mataram, Indonesia Mulyanto Á K. Surayah West Nusa Tenggara Hepatitis Laboratory, Mataram, Indonesia F. Tsuda Department of Medical Sciences, Toshiba General Hospital, Tokyo, Japan Present Address: F. Tsuda Aikawa Internal Medicine Hospital, Ibaraki, Japan K. Ichiyama Á M. Takahashi Á H. Okamoto (&) Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan e-mail: hokamoto@jichi.ac.jp 123 Arch Virol DOI 10.1007/s00705-009-0406-9