A case of chronic hepatitis C developing insulin-dependent diabetes mellitus associated with various autoantibodies during interferon therapy

Abstract

We report a case of chronic hepatitis C presenting insulin-dependent diabetes mellitus (IDDM) associated with various autoantibodies including possible anti-insulin receptor antibody (AIRA) during interferon (IFN) therapy. A 57-year-old man having chronic hepatitis C virus (HCV) infection with chronic thyroiditis received IFN therapy. The thyroid function was well-controlled by administration of thyroid hormone, although thyroid autoantibodies were positive. At 15 weeks after starting IFN (reaching 530 million units of total dose), marked thirst happened, with increased fasting plasma glucose level (488 mg/dl) and decreased daily urinary C peptide immunoreactivity level (less than 4.2 μg/day). IDDM occurred with anti-nuclear antibody (ANA), anti-DNA antibody and possible AIRA, and thyroid autoantibodies titers increased, but without pancreatic islet cell antibody and anti-glutamic acid decarboxylase antibody. Administration of IFN was stopped and insulin treatment was started, but plasma glucose level was not controlled well. AIRA became negative 2 months later, however, insulin antibody (IA) was positive when tested after 18 months. Serum HCV RNA has been negative, and a normal level of serum transaminase has been observed since IFN therapy. It is likely that IFN therapy induced the immunological disturbance and resulted in occurrence of various autoantibodies and IDDM in the patient.

Introduction

Interferon (IFN) therapy has been applied on not only several malignancies but also chronic hepatitis due to hepatitis C virus (HCV) because of its anti-tumor and anti-viral effects. Systemic side effects of IFN therapy can involve numerous organ systems. These adverse reactions include a flu-like syndrome, hematological abnormalities, cardiovascular and central nervous symptoms, gastrointestinal symptoms, diabetes mellitus, autoimmune disorders, pulmonary dysfunction, depression and retinopathy [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15]. Frequency of glucose intolerance and its progress is reported to be about 0.1–0.6% [13], [14], [15]. Thus, among adverse reactions during IFN therapy, insulin-dependent diabetes mellitus (IDDM) is relatively rare and few cases with anti-pancreatic islet cell antibody (ICA) or anti-glutamic acid decarboxylase (GAD) antibody have been reported [1], [2], [3], [4], [5], [6], [7]. We report a case presenting IDDM associated with various autoantibodies including possible anti-insulin receptor antibodies (AIRA) during IFN therapy for chronic hepatitis C.