Development of insulin-dependent diabetes mellitus in a patient with chronic hepatitis C during therapy with interferon-alpha

Interferon (IFN)-alpha is used for the treatment of chronic viral hepatitis . It has been associated with various forms of autoimmune disease, e.g. aut oimmune hepatitis, Hashimoto thyroiditis and insulin-dependent diabetes mel litus. Further, an increase of insulin resistance and development of non-in sulin-dependent diabetes mellitus has been described after treatment with I FN-alpha. Several studies have investigated the induction of different auto immune markers by IFN-alpha, but only few specified patients who developed insulin-dependent diabetes mellitus. We report the case of a 37-year-old ma n with chronic hepatitis C who was treated with IFN-alpha plus ribavirin. T hirty weeks after the start of treatment, the patient developed insulin-dep endent diabetes mellitus and therapy was withdrawn. HLA typing showed an HL A-DR1,3 phenotype. At manifestation of diabetes mellitus, the C-peptide lev el was 0.37 ng/ml (normal range 0.5-3 ng/ml). The patient had a positive fa mily history for type 2 diabetes. Several autoimmune markers were investiga ted before, during and 6 months after withdrawal of antiviral treatment. Hi gh titres of glutamic acid decarboxylase (GAD) antibodies were present befo re therapy. A significant increase in titres of islet cell antibodies, pari etal cell antibodies and sperm antibodies was present after 14 weeks of IFN -alpha treatment. Six months after withdrawal of IFN-alpha therapy, these a ntibodies had significantly decreased whereas GAD antibodies remained uncha nged. There was no clinical sign of any other autoimmune disease. Our data show that, in patients with a predisposition to insulin-dependent diabetes mellitus, the disease may become manifest as a side-effect during therapy w ith IFN-alpha. Several pathogenetic factors may be involved in this process , and, in addition to IFN-alpha, hepatitis C itself may induce autoimmune m echanisms. We conclude that screening for autoantibodies specific for type 1 diabetes should be performed before the start of IFN-a treatment. In pati ents found to be at increased risk of developing diabetes mellitus type 1, monitoring of titres of these antibodies during therapy could help to asses s the individual risk-benefit ratio of IFN-alpha treatment. Eur J Gastroent erol Hepatol 13:295-298 (C) 2001 Lippincott Williams & Wilkins.