Relationships between 34 HLA-A, HLA-B and HLA-DR antigens and three serological markers of viral infections in alcoholic cirrhosis

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Abstract
In order to study the genetic risk of alcoholic cirrhosis, the frequency of 26 HLA-A and -B antigens was compared in 184 normal controls, 175 alcoholic cirrhotic patients and 83 alcoholic patients with hepatic steatosis of carefully selected ethnic origin. Eight HLA-DR antigens were also determined in 95 subjects of the normal control group and 63 patients of the alcoholic cirrhosis group. The incidence of hepatitis B virus antibodies (anti-HBc and anti-HBs) was defined in 74 patients of the alcoholic steatosis group, 170 patients of the alcoholic cirrhosis group and 111 normal controls different from the previously mentioned normal control group. The incidence and the titers of cytomegalovirus and rubella antibodies were also determined in 93 patients of the alcoholic cirrhosis group and the 111 normal controls. Serum immunoglobulin concentrations were measured in the same 93 cirrhotic patients. Compared with the controls, the alcoholic cirrhosis group revealed a significantly higher frequency of HLA-B15 (21.7 vs. 9.8%, p<0.00025, corrected p<0.050) and HLA-DR4 (38.1 vs. 17.9%, p<0.005, corrected p<0.050) and a significantly lower frequency of HLA-B13 (2.9 vs. 11.4%, p<0.025, corrected p<0.050). As for the frequency of all other HLA antigens, there was no significant difference between the three groups (normal controls, alcoholic cirrhosis and alcoholic steatosis). In the alcoholic cirrhosis group, the incidence of hepatitis B virus antibodies was higher in B15(+) patients (41.6%) than in B15(−) ones (19.4%, p<0.010) and in DR4(+) patients (50%) than in DR4(−) ones (15.4%, p<0.005). In the control and steatosis groups, there was no significant difference. In the alcoholic cirrhosis group, a significantly higher incidence of anticytomegalovirus was also observed in B15(+) patients (95.0%) than in B15(−) patients (69.9%, p <0.050), as well as significantly higher titers (p<0.050) of anticytomegalovirus and rubella and significantly higher IgG concentrations (p<0.025). All of these significant differences were not found in the control group. These results suggest that: (i) there is a genetic predisposition in alcoholic cirrhosis which may be associated with the presence of HLA-B 15 and DR4 antigens, and (ii) the higher incidence of hepatitis B virus antibodies in B15(+) and DR4(+) cirrhotic patients may be the result of differences in their immune responsiveness when compared to B15(−) and DR4(−) patients.