A complete genomic analysis of hepatitis B virus genotypes and mutations in HBeAg-negative chronic h

February 11, 2008

Journal of Viral Hepatitis (OnlineEarly Articles).

doi:10.1111/j.1365-2893.2008.00967.x

Abstract

A complete genomic analysis of hepatitis B virus genotypes and mutations in

HBeAg-negative chronic hepatitis B in China

L. Zhu11Department of Medicine and Therapeutics and Institute of Digestive

Disease, C. -H. Tse11Department of Medicine and Therapeutics and Institute of

Digestive Disease, V. W. -S. Wong11Department of Medicine and Therapeutics and

Institute of Digestive Disease, A. M. -L. Chim11Department of Medicine and

Therapeutics and Institute of Digestive Disease, K. -S. Leung22Department of

Engineering and Computer Sciences, The Chinese University of Hong Kong, Honkong,

China and H. L. -Y. Chan11Department of Medicine and Therapeutics and Institute

of Digestive Disease1Department of Medicine and Therapeutics and Institute of

Digestive Disease; and 2Department of Engineering and Computer Sciences, The

Chinese University of Hong Kong, Honkong, China

Henry LY Chan, MD, Department of Medicine and Therapeutics, 9/F Prince of Wales

Hospital, Shatin, Hong Kong SAR, China. E-mail: hlychan@...

ALT, alanine aminotransferase; BMI, body mass index; HBeAg, hepatitis B e

antigen; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; PCR, polymerase

chain reaction.

Abstract

Summary. We aimed to study the distribution of hepatitis B virus (HBV)

genotypes/subgenotypes in different parts of China and their clinical impact on

the severity of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B.

Residual serum samples from a cohort of HBeAg-negative chronic hepatitis B

patients in Hong Kong, Shanghai and Beijing were studied. Complete HBV genomic

sequencing was performed for phylogenetic tree analysis and determination of HBV

mutations was carried out. Mutations associated with severe liver fibrosis

(Ishak score 4 or more) were selected by computerized information gain criteria.

Genotype B (all subgenotype Ba) HBV was present in 19 of 45 (42%), 12 of 31

(39%) and 5 of 25 (20%) patients in Hong Kong, Shanghai and Beijing,

respectively (P = 0.16). Ninety-seven per cent of genotype C HBV in Shanghai and

Beijing belonged to subgenotype Ce whereas 69% of genotype C patients in Hong

Kong belonged to subgenotype Cs (P < 0.001). Patients infected by subgenotype Cs

had the lowest serum albumin and highest alanine aminotransferase levels

compared with subgenotype Ce and Ba. Patients infected by subgenotype Cs also

had more severe histological necroinflammation than subgenotype Ce. Two HBV

mutations were identified to associate with severe liver fibrosis (G2858C and

C2289A) and one mutation was protective against severe liver fibrosis (T2201C).

The T2201C mutation was found exclusively among patients (21 of 46 patients,

45%) infected by HBV subgenotype Ce. The clinical differences in HBeAg-negative

chronic hepatitis B in China may be influenced by different distribution of

subgenotype C HBV.

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February 11, 2008