LAUSR

Interferon therapy can increase the risk of type 1 diabetes (T1D) in patients with hepatitis C. Fulminant T1D (FT1D) is a novel subtype of T1D characterized by extremely rapid progression. However, the relationship between interferon therapy and FT1D remains to be determined. Herein, we report a case of FT1D in a 51-year-old Chinese woman receiving peginterferon α-2a therapy for hepatitis C. This study was approved by the Human Ethics Committee of Central South University and was performed in accordance with ethical standards. Informed consent was obtained from the patient. The patient, with no family or personal history of diabetes, was admitted to the emergency room 1 year after initiation of peginterferon α-2a treatment with a complaint of repeated vomiting for 1 day. Laboratory tests identified severe diabetic ketoacidosis (blood glucose 25.7 mmol/L, pH 7.21, and ketones 6.11 mmol/L); C peptide was undetectable (<5.5 pmol/L) and the patient’s HbA1c level was 6.7% (50 mmol/mol). These findings met the main diagnostic criteria for FT1D proposed by the Japan Diabetes Society. Meanwhile, other immune disorders were identified, specifically: (i) the patient was positive for glutamic acid decarboxylase autoantibody (GADA) and islet antigen 2 autoantibody (IA2A); (ii) hypothyroidism due to Hashimoto thyroiditis with significantly elevated thyroid peroxidase antibody; (iii) megaloblastic anemia (hemoglobin [Hb] 65 g/L, mean corpuscular volume 117.9 fL, mean corpuscular Hb 319 g/L); and (iv) low complement 3 (C3) and complement 4 (C4) levels. Peginterferon α-2a was withdrawn and the patient was reviewed at 3monthly intervals (Table 1). The patient recovered from hypothyroidism and megaloblastic anemia without longterm medication gradually. However, C peptide levels were persistently low. Fortunately, hepatitis C virus (HCV) RNA and liver function were normal during the follow-up period. Human leukocyte antigen (HLA) sequencing identified HLA*DQA1 03, DQB1*0303, and DRB1*0901 alleles. Fulminant T1D is a rare form of T1D that is caused, in particular, by peginterferon α-2a in hepatitis C. A nationwide survey in Japan found that the prevalence of FT1D developing during or shortly after interferon therapy in T1D was 5.5% (5/91). However, the clinical features of FT1D are much worse than classical T1D, such as extremely severe onset, rapid progress, and poor prognosis. So, it is imperative that clinicians identify FT1D and provide treatment. In the present case, the patient was found to be positive for GADA, and HLA sequencing revealed the presence of DQB1*0303 and DRB1*0901 alleles. A national survey in Japan found that frequencies of the DRB1*04:05– DQB1*04:01 and DRB1*09:01–DQB1*03:03 haplotypes were significantly higher in subjects positive for GADA than in control subjects (32.6% vs 14.2% and 25.4% vs 13.7%, respectively). However, in FT1D patients with GADA, the frequency of DRB1*09:01-DQB1*03:03 only (and not DRB1*04:05-DQB1*04:01) was significantly higher than in control subjects (44.0% vs 13.7%; Pcorrected < 0.05, odds ratio 5.0). Therefore, we speculate that the genetic background of HLA DRB1*09:01–DQB1*03:03 may contribute to the production of GADA in some FT1D patients. In addition to autoimmune FT1D, many other wellrecognized negative effects of peginterferon α-2a therapy were found in the present patient. Immediate withdrawal of peginterferon α-2a and proper treatment enabled the patient to recover from hypothyroidism and megaloblastic anemia, but not FT1D. Because of the severity of F1TD and its poor prognosis, we call for extensive assessment and monitoring of glucose tolerance in chronic hepatitis C patients on interferon therapy.