Viral genotype and hepatitis B virus DNA levels are correlated with histological liver damage in HBeAg-negative chronic hepatitis B virus infection.
OBJECTIVE
We aimed to study the relationship between the hepatitis B virus (HBV) genotypes, core promoter/precore stop codon mutations, and histological liver damage among hepatitis B e antigen (HBeAg)-negative patients.


METHODS
Liver biopsy specimens of 55 HBeAg-negative chronic HBV-infected patients were studied. A histological activity index was scored for degree of necroinflammation (HAI-NI) and fibrosis (HAI-F) as described by Knodell et al. HBV DNA was determined by a cross-linking assay and polymerase chain reaction (PCR) at the core promoter/precore region and the S region. PCR-positive samples were directly sequenced for core promoter and precore mutations and examined by restriction fragment length polymorphism for genotyping.


RESULTS
Forty-one males and 14 females at a median age of 43 were studied. HBV DNA was detectable in 32 (58%) and 37 (67%) patients by the cross-linking assay and PCR, respectively, at the time of liver biopsy. The median (range) HAI-NI and HAI-F scores were 5 (1-10) and 2 (0-4), respectively. HBV DNA detectable by either the cross-linking assay or PCR was associated with a higher HAI-NI score. Eleven and 31 patients had genotypes B and C HBV, respectively. Genotype C HBV was associated with higher HAI-NI than genotype B HBV. Core promoter mutations and precore stop codon mutation were detected in 74% and 40% patients, respectively, but they were not associated with higher HAI-NI or HAI-F scores.


CONCLUSIONS
Detectable HBV DNA and genotype C HBV, but not core promoter or precore stop codon mutations, are associated with more severe liver damage in HBeAg-negative patients.
Chan
Henry Lik-Yuen
HL
Department of Medicine, The Chinese University of Hong Kong.
Tsang
Steven Woon-Choi
SW
Liew
Chook-Tiew
CT
Tse
Chi-Hang
CH
Wong
May-Ling
ML
Ching
Jessica Yuet-ling
JY
Leung
Nancy Wai-Yee
NW
Tam
John Siu-Lun
JS
Sung
Joseph Jao-Yiu
JJ
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D001707:Biopsy, Needle; D046508:Culture Techniques; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics*; D005260:Female; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000473:pathology* / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011336:Probability; D011401:Promoter Regions, Genetic; D012680:Sensitivity and Specificity; D012698:Serologic Tests; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
D004279:DNA, Viral; D006513:Hepatitis B e Antigens