HLA-DR5 antigen. A genetic factor influencing the outcome of hepatitis C virus infection?

Prognosis may be quite different among individuals infected with hepatitis C virus (HCV): a chronic liver disease is believed to occur in half the patients while in the other half there are no signs of histologic progression of liver damage. The host immune response might play an important role in such different outcomes. A relationship has been shown between HLA genes and immune response to viral hepatitis B, but to our knowledge, no evidence of an association with HCV has been reported so far. We investigated whether HLA class II alleles might influence the outcome of HCV infection.

Eighty-seven individuals, positive for anti-HCV by second-generation enzyme-linked immunosorbent assay and recombinant immunoblot assay tests, enrolled from May 1, 1991, to June 31, 1992, were evaluated. Thirty-six were symptom-free subjects found to have HCV antibodies when screened for blood donation: they all had normal results of liver function tests, normal results of physical examination, and normal hepatobiliary ultrasonography. Fifty-one were patients diagnosed as having a chronic liver disease by percutaneous liver biopsy specimen; histologic assessment was chronic persistent hepatitis in 15, chronic active hepatitis in 28, and liver cirrhosis in eight. A group of 231 donors of platelets and bone marrow, negative for anti-HCV, was used as a control population. All participants were typed for HLA class II antigens (DR and DQ) using National Institutes of Health recommended microlymphocytotoxicity test and were followed up by means of alanine aminotransferase and HCV testing for at least 1 year.

Frequency of HLA-DR5 antigen was higher in symptom-free anti-HCV-positive individuals (52.8%) than among HCV-related patients with chronic liver disease (13.7%). The difference was statistically significant (corrected P value = .005; 95% confidence interval, 19.6% to 58.6%); between DR5 and long-term evolution of hepatitis C, there was a negative association (relative risk = 0.142). Moreover, frequency of HLA-DR5-positive subjects appeared to be inversely proportional to severity of liver disease (52.8% in symptom-free patients, 26.6% in patients with chronic persistent hepatitis, 10.7% in patients with chronic active hepatitis, and 0% in patients with liver cirrhosis, P < .001).

Our results point to a strict relationship between HLA haplotype and ability of immune response to influence the outcome of HCV infection. Presence of HLA-DR5 antigen appears as a protective factor against a severe outcome of chronic infection, being correlated with a benign evolution of the infection, often asymptomatic, or a less severe chronic liver disease.