[Viral factors influencing histological changes of HBeAg-negative chronic hepatitis B patients with persistently normal serum ALT levels].
OBJECTIVE
To investigate the correlation between viral factors and liver histological changes of HBeAg-negative chronic hepatitis B patients with persistently normal serum ALT levels (PNAL).


METHODS
HBV DNA level, HBV genotype, basal core promoter (BCP) and precore mutation were examined in 52 HBeAg-negative chronic hepatitis B patients with PNAL (defined as normal ALT measured on at least 3 occasions in the intervals of about two months over a period of 12 months or more prior to the biopsy).


RESULTS
Subjects with both BCP and precore mutations had significantly higher HBV DNA levels than those without mutations [(4.9+/-1.4) vs (4.1+/-1.1) log(10)copies/ml, t = 2.308, P < 0.05]. A higher proportion of patients with histological activity index (HAI) > or = to 4 was found in patients with both mutations (32.1% vs 16.7%) than in patients without mutation, however, the proportion of patients with histological activity index (HAI) > or = to 3 in patients with mutations was not significantly different from that in patients without mutations (14.3% vs. 12.5%, x(2)=0.000, P > 0.05). In patients without precore or BCP mutations, there was a strong positive correlation between viral load and liver inflammation as well as fibrosis (precore: r=0.626, 0.592, P < 0.01; BCP: r=0.730, 0.641, P < 0.01). In patients without both mutations, HBV DNA has shown a high accuracy for predecting fibrosis (F > or = 3) (AUC = 0.905, 95% CI: 0.771-1.039, P < 0.05) with the cutoff value of 4.5 log(10) copies/ml (sensitivity = 1.000, specificity = 0.778, PPV = 42.9%, NPV = 100.0%). Results of both genotypes and mutations were successfully obtained in 40 samples with HBV DNA is > or = to 10(4) copies/ml. The higher viral load was observed in the patients with genotype B than genotype C (5.1 vs 4.3 log(10)copies/ml, t = 2.059, P < 0.05), but no difference was seen of liver pathologic changes between these two genotypes.


CONCLUSIONS
Virus harboring both BCP and precore mutants has the higher replication level than wild type virus. 32.1% and 14.3% of the patients with both mutations have moderate or severe inflammation and fibrosis. There was a strong positive correlation between viral load and liver histological changes in patients without precore or BCP mutations, and viral load shows a high accuracy for predecting significant fibrosis (F > or = 3).
Yang
Yan-hua
YH
Department of Infectious Diseases, Ruijing Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Xie
Qing
Q
Wang
Hui
H
Zhou
Hui-juan
HJ
Gui
Hong-lian
HL
Cai
Wei
W
Guo
Si-min
SM
Yu
Hong
H
Guo
Qing
Q
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001483:Base Sequence; D002353:Carrier State / Q000473:pathology / Q000821:virology; D004279:DNA, Viral / Q000097:blood / Q000235:genetics*; D005260:Female; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000473:pathology / Q000821:virology*; D006801:Humans; D008099:Liver / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D019562:Viral Load
D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase