Interferon (IFN)-alpha is used for the treatment of chronic viral
hepatitis. It has been associated with various forms of
autoimmune disease, e.g.
autoimmune hepatitis,
Hashimoto thyroiditis and
insulin-dependent diabetes mellitus. Further, an increase of
insulin resistance and development of
non-insulin-dependent diabetes mellitus has been described
after treatment with IFN-alpha. Several studies have investigated the induction of different autoimmune markers by IFN-alpha, but only few specified patients who developed
insulin-dependent diabetes mellitus. We report the case of a 37-year-old man with
chronic hepatitis C who was treated with IFN-alpha plus
ribavirin. Thirty weeks after the start of treatment, the patient developed
insulin-dependent diabetes mellitus and
therapy was withdrawn. HLA typing showed an HLA-DR1,3 phenotype. At manifestation of
diabetes mellitus, the
C-peptide level was 0.37 ng/ml (normal range 0.5-3 ng/ml). The patient had a positive family history for
type 2 diabetes. Several autoimmune markers were investigated before, during and 6 months after withdrawal of
antiviral treatment. High titres of
glutamic acid decarboxylase (GAD)
antibodies were present before
therapy. A significant increase in titres of islet cell
antibodies, parietal cell
antibodies and sperm
antibodies was present after 14 weeks of IFN-alpha treatment. Six months after withdrawal of IFN-alpha
therapy, these
antibodies had significantly decreased whereas GAD
antibodies remained unchanged. 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 with IFN-alpha. Several pathogenetic factors may be involved in this process, and, in addition to IFN-alpha,
hepatitis C itself may induce autoimmune mechanisms. We conclude that screening for
autoantibodies specific for
type 1 diabetes should be performed before the start of IFN-alpha treatment. In patients found to be at increased risk of developing
diabetes mellitus type 1, monitoring of titres of these
antibodies during
therapy could help to assess the individual risk-benefit ratio of IFN-alpha treatment.