乙型肝炎病毒感染临床结局与HLA-DR基因的相关性研究

Study of the association between the clinical outcomes and HLA-DR genes in the hepatitis B virus infection subjects

目的:探讨乙型肝炎病毒(HBV)感染临床结局与人类白细胞抗原DR(HLA-DR)基因间的相关性。方法:选择急性乙型肝炎(AHB)76例,慢性乙型肝炎(CHB)102例,乙肝后肝硬化(LC)38例,肝细胞癌(HCC)34例,用聚合酶链反应-序列特异性引物法(PCR-SSP)检测HLA-DR基因型。结果:HLA-DR1基因型频率在LC和HCC组显著高于AHB组(χ2=8.495,P=0.004),较CHB组也显著升高(χ2=5.667,P=0.017);HLA-DR8基因型发生频率在CHB、LC和HCC三个HBV慢性感染组间无显著差异(P=0.034),而在AHB组显著低于HBV慢性感染组(χ2=8.830,P=0.003);HLA-DR13基因型频率在AHB组显著高于CHB组(χ2=26.876,P=0.000)及LC和HCC组(χ2=6.413,P=0.011),而LC和HCC组又高于CHB组(χc2=6.479,Pc=0.011)。结论:HLA-DR1基因型可能与HBV相关的肝硬化和肝细胞癌的发生有关,而HLA-DR8基因型则对HBV感染的慢性化有促进作用,HLA-DR13基因型可有助于HBV的清除,但在HLA-DR13阳性的HBV慢性感染者发生肝硬化和肝细胞癌的风险增加。

Objective： To study the association between the clinical outcomes and HLA-DR genes in the hepatitis B virus infection subjects. Methods： HLA-DR alleles in 76 cases acute hepatitis B, 102 cases chronic hepatitis B, 38 cases liver cirrhosis and 34 hepatocellular carcinoma with HBV infection, were detected by polymerase chain reaction-sequence specific primer （PCR-SSP） technique. Results： The frequency of HLA-DR1 gene was significantly higher in liver cirrhosis and hepatocellular carcinoma group than that in acute hepatitis B （x^2=8.495 ,P=0.004） and that in chronic hepatitis B （x^2=5.667 ,P=0.017）. There was no difference in the frequencies of HLA-DR8 gene among chronic hepatitis, liver cirrhosis and hepatocellular carcinoma groups （P=0.034）, but the frequency in acute hepatitis B was significantly lower than that in the chronic HBV infection subjects （X^2=8.830,P=0.003）. The frequency of HLA-DR13 gene was significantly higher in acute hepatitis B than that in chronic hepatitis B （x^2=26.876,P=0.000） and that in liver cirrhosis and hepatocellular carcinoma （x^2=6.413 ,P=0.011）, and the frequency of HLA-DR13 gene was markedly higher in liver cirrhosis and hepatocellular carcinoma than that in chronic hepatitis B （x^2=6.479 ,Pc=0.011）. Conclusion： HLA-DR1 may be closely associated with the risk of liver cirrhosis and hepatocellular in the HBV infection subjects; HLA-DR8 may contribute to the chronie HBV infection; HLA-DR13 may contribute to the clearance of HBV, but the risk of liver cirrhosis or hepatocellular carcinoma increases in the HLA-DR13 positive subjects with chronic HBV infection.