Latent autoimmune hepatitis triggered during interferon therapy in patients with chronic hepatitis C

Interferon can induce autoantibodies and autoimmune reactions. This study reviewed the clinical, serological, and HLA phenotypical features of patients who developed autoimmune hepatitis during interferon therapy for chronic hepatitis C, analyzing their response to immunosuppressive treatment.

The diagnosis of chronic hepatitis C was based on positivity for viral RNA and a liver biopsy specimen obtained before interferon treatment. Sera were tested for autoantibodies by indirect immunofluorescence assay. HLA typing was performed by applying a standard microlymphocytotoxicity method.

Of 144 patients with chronic hepatitis C treated with interferon, 7 women deteriorated during treatment; serum transaminase, gamma-globulin, and immunoglobulin G levels increased; and serum autoantibodies became positive. Interferon was interrupted, a diagnosis of autoimmune hepatitis was established, and immunosuppressive therapy was initiated. All patients responded to this treatment. The 7 patients had similar HLA typing to those with autoimmune hepatitis, with DR4 in 2 patients (67%) with type 2 autoimmune hepatitis, and with DR3 and DR52 in 2 (50%) and 4 (100%) patients, respectively, with type 1 autoimmune hepatitis; additionally, 5 patients (71%) had DQ2, and 4 (57%) had both DR52 and DQ2.

In female patients with chronic hepatitis C, a genetic susceptibility to autoimmune hepatitis may exist, possibly triggered by immunostimulating effects during interferon therapy. Immunosuppressive treatment has been well tolerated and seems to be effective.