Impact of precore and core promoter mutations on hepatic histology in patients with chronic hepatitis B.
BACKGROUND
The details of liver histology of patients with precore and core promoter mutations are still not clear.


OBJECTIVE
To determine the role of precore and core promoter mutations in liver histology in Chinese patients with chronic hepatitis B.


METHODS
Intrahepatic hepatitis B virus DNA (by COBAS Amplicor hepatitis B virus Monitor test) and precore and core promoter mutations (by a line probe assay) were measured in 54 chronic hepatitis B patients. Expression of hepatitis B core antigen, hepatitis B e antigen and hepatitis B surface antigen was determined by immunohistological staining. Histological activity index was scored according to Knodell's criteria.


RESULTS
Compared with patients without core promoter mutations, patients with core promoter mutations had more severe intrahepatic inflammation and fibrosis, and more cytoplasmic expression of hepatitis B core antigen (P = 0.028). No such differences were found in patients with and without precore mutations. Logistic regression showed that core promoter mutations were independently associated with cytoplasmic expression of hepatitis B core antigen (P = 0.026). Intrahepatic hepatitis B virus DNA levels correlated with serum hepatitis B virus DNA levels (r = 0.71, P < 0.001) and the percentage of hepatitis B core antigen-positive hepatocytes (r = 0.37, P = 0.047), but had no correlation with serum alanine aminotransferase levels nor the degree of inflammation and fibrosis.


CONCLUSIONS
Patients with core promoter mutations had more severe inflammation and fibrosis, and more frequent cytoplasmic expression of hepatitis B core antigen. This suggested that core promoter mutations might cause more serious liver disease.
Yuan
H-J
HJ
Department of Medicine, The University of Hong Kong, Queen Mary Hospital. mfyuen@hkucc.hku.hk
Yuen
M-F
MF
Ka-Ho Wong
D
D
Sum
S-M
SM
Sablon
E
E
Ng
I O
IO
Lai
C-L
CL
D000328:Adult; D000368:Aged; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006512:Hepatitis B Core Antigens / Q000378:metabolism; D006513:Hepatitis B e Antigens / Q000378:metabolism; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics
D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens