Phylogenetic, virological, and clinical characteristics of genotype C hepatitis B virus with TCC at codon 15 of the precore region.
Hepatitis B virus (HBV) with T-1856 of the precore region is always associated with C-1858 (i.e., TCC at nucleotides 1856 to 1858), and it is reported only in genotype C HBV isolates. We aimed to investigate the phylogenetic, virological, and clinical characteristics of HBV isolates bearing TCC at nucleotides 1856 to 1858. We have previously reported on the presence of two major subgroups in genotype C HBV, namely, HBV genotype Cs (Southeast Asia) and HBV genotype Ce (Far East). We have designed a novel 5' nuclease technology based on the nucleotide polymorphism (C or A) at nucleotide 2733 to differentiate the two genotype C HBV subgroups. The mutations at the basal core promoter and precore regions were analyzed by direct sequencing. Among 214 genotype C HBV-infected patients, 31% had TCC, 37% had CCC, 3% had CTC, and 29% had CCT at nucleotides 1856 to 1858. All except one HBV strain with TCC at nucleotides 1856 to 1858 belonged to subgroup Cs, which has been reported only in Hong Kong; Guangzhou, China; and Vietnam. HBV with TCC at nucleotides 1856 to 1858 was associated with the G1898A mutation (64%). Patients infected with HBV harboring TCC had more liver cirrhosis than those infected with HBV harboring CCC (18% versus 5%; P = 0.008), and more of the patients infected with HBV harboring TCC were positive for HBeAg (58% versus 36%; P = 0.01) and had higher median alanine aminotransferase levels (65 IU/liter versus 49 IU/liter; P = 0.006); but similar proportions of patients infected with HBV harboring TCC and those infected with HBV harboring CCT had liver cirrhosis (18% versus 13%; P = 0.43). In summary, we report that HBV with TCC at nucleotides 1856 to 1858 of the precore region might represent a specific HBV strain associated with more aggressive liver disease than other genotype C HBV strains.
Chan
Henry Lik-Yuen
HL
Department of Medicine and Therapeutics and Institute of Digestive Diseases, 9/F Prince of Wales Hospital, The Chinese University of Hong Kong, 30-32 Ngan Shing Street, Shatin, Hong Kong, Hong Kong. hlychan@cuhk.edu.hk
Tse
Chi-Hang
CH
Ng
Eddie Yuen-Tok
EY
Leung
Kwong-Sak
KS
Lee
Kin-Hong
KH
Tsui
Stephen Kwok-Wing
SK
Sung
Joseph Jao-Yiu
JJ
D001483:Base Sequence; D003062:Codon / Q000235:genetics; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006509:Hepatitis B / Q000821:virology; D006512:Hepatitis B Core Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D009690:Nucleic Acid Conformation; D010802:Phylogeny; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D014774:Virulence / Q000235:genetics
D003062:Codon; D004279:DNA, Viral; D006512:Hepatitis B Core Antigens