Abnormal immunity and gene mutation in patients with severe hepatitis-B.
OBJECTIVE
To evaluate the abnormal immunity and gene mutation at precore 1896 site in patients with severe hepatitis-B.


METHODS
This study included 23 patients with severe hepatitis-B, 22 patients with acute hepatitis-B and 20 controls. Mutation at precore 1896 site of HBV gene was confirmed with restriction fragment length polymorphism (RFLP) analysis. Cytokines including TNF-alpha, IFN-gamma, IL-6, and IL-8 were measured with ELISA, and T subgroups were detected with alkaline phosphatase anti alkaline phosphatase (APAAP) technique.


RESULTS
In patients with severe hepatitis-B, the infective rate of HBV mutant strain was 52.5 % (12/23), and only one patient with acute hepatitis-B was infected with the mutant strain. The percentage of CD8+ T lymphocyte was obviously lower (0.16+/-0.02 %) and the ratio of CD4+/CD8+ was obviously higher (2.35+/-0.89) in mutant group than in wild-type group (0.28+/-0.05 % and 1.31+/-0.18 %, respectively, P<0.01 or P<0.05). The levels of cytokines in patients with severe hepatitis-B were higher (TNF-alpha 359.0+/-17.2 ng/L, IFN-gamma 234.7+/-16.5 ng/L, IL-6 347.5+/-31.3 ng/L, IL-8 181.1+/-19.6 ng/L) than those in acute hepatitis-B (TNF-alpha 220.6+/-8.9 ng/L, IFN-gamma 174.9+/-12.0 ng/L, IL-6 285.8+/-16.5 ng/L, IL-8 118.4+/-5.1 ng/L, P<0.01 or 0.05). In patients with severe hepatitis-B, the levels of IFN-gamma and IL-6 were higher in mutant group (273.4+/-26.6 ng/L, 387.7+/-32.5 ng/L) than in wild-type group (207.8+/-12.8 ng/L, 300.9+/-16.3 ng/L). The mortality of patients infected with HBV mutant strain was higher (100 %) than that with wild-type (0.9 %).


CONCLUSIONS
In severe hepatitis-B, the infective rate of HBV mutant strain was high. The mutant strain induces more severe immune disorders in host, resulting in the activation of lymphocyte and release of cytokines. HBV DNA mutates easily in response to the altered immunity. Ultimately liver damage is more prominent.
Wang
Jing-Yan
JY
Department of Infectious Diseases, the Second Hospital, China Medical University, Shenyang 110004, Liaoning Province, China.
Liu
Pei
P
D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D005814:Genes, Viral / Q000235:genetics*; D006509:Hepatitis B / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D007154:Immune System Diseases / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009154:Mutation