Study On The Association Between Severe Chronic Hepatitis B And HLA-DRB1*1301,1302 Allele

Hepatitis B is a common infectious disease and can result in serious consequences. There are almost 350 million hepatitis B virus (HBV) carriers in the world.However, different patients with HBV show different clinical features. Fulminant hepatitis B is a lethal manifestation for patients with HBV with high mortality rate (80%). This may result from the fierce hypersensitive immune response of host to virus, which can lead to serious hepatocytes necrosis and apoptosis , and then ultimate liver failure. It is generally believed that different manifestations after infected with HBV are due to the hosts'different immune response ability. Because human leucocyte antigen (HLA) complex can regulate the immune response , the study on the association between HLA complex and HBV infection is becoming more and more important. Through interaction with their ligands, CD8 and CD4,HLA type I and type II antigens ,which function in stabilizing and promoting the interactions of the immunocytes, can enhance the initiation level and effect of the immune response. And the specific genotypes of HLA complex may affect the hosts'immune response after infected with HBV , leading to fatal fulminant hepatitis.Objective (1) To explore the relationship between the severe chronic hepatitis B and HLA-DRB1* 1301,1302 allele by investigating the incidence rate of HLA-DRB1* 1301,1302 allele in patients with severe and common chronic hepatitis B, then to provide immuno-genetic knowledge for the early diagnosis and prevention of the severe chronic hepatitis B. (2) To investigate the role of immune response in the deterioration of chronic hepatitis B,and detect the mechanism underlying the effects of HLA DRB1*1301,1302 allele on the development of the severe chronic hepatitis B.Methods (1) Genomic DNA was extracted from white blood cells of patients using traditional phenol-chloroform method. HLA-DRB 1*1301, 1302 allele was analyzed by polymerase chain reaction /sequence specific primer(PCR-SSP) technique, with the specific primers of HLA-DRB1*1301, 1302 designed by software, then the PCR products were purified and sequenced. (2)Detecting HBVDNA level and monitoring its change in the serum of the patients by fluorescent. All of the statistical analyses were calculated by SPSS 10.0 statistical software.Result (1) Allele frequencies of HLA-DRB1*1301, 1302 in the severe chronic hepatitis B group and chronic hepatitis B group were 82.6% and 30%, respectively .The frenquency of HLA-DRB 1*1301, 1302 allele in the severe chronic hepatitis B group was markedly higher than that hi the chronic hepatitis B group. (82.6%vs 30%, x2=14.459, p <0.05, RR=11.083) .(2) When hospitalization,the medians of the HBVDNA of severe chronic hepatitis B group and chronic hepatitis B group were 1.7*106 and 9.9xl03copies/ml, respectively. There was no statistical significance(z=-0.125, p=0.901 > 0.05).While when discharge, the medians of the HBV DNA of two groups were l.SxlO4 and 1.2 106copies/ml, respectively.The titer of HBV DNA in the severe chronic hepatitis B group was significantly lower than that in chronic hepatitis B group(z=-2.807, p=0.005 < 0.05).In the period of hospitalization, the clearance of the HBV DNA is much more in severe chronic hepatitis B group than in chronic hepatitis B group(t=3.618, p=0.006 < 0.05).Conclusion (1)HLA-DRB1*1301, 1302 is closely associated with the suseptibility to severe chronic hepatitis, and may be valuable marker to judge patients'conditions and for prognosis prediction. (2) During the deterioration of chronic hepatitis B, the titer of HBV DNA was decreased significantly. Hosts'immune response took part in not only the non-complete clearance of the HBV DNA but olso the acceleration of the fulminant hepatitis occurrence, and HLA-DRB1*1301, 1302 allele may affect the occurrence of fulminant hepatitis by changing the hosts'immune response.