Trajectories of anti-islet autoantibodies before development of type 1 diabetes in interferon-treated hepatitis C patients. Case reports and a literature review.
Interferon-alpha (IFN-α) is widely used in the treatment of viral hepatitis, however, it is known that IFN-α therapy may induce type 1 diabetes. We report here on two cases of chronic viral hepatitis C who developed autoimmune type 1 diabetes during Peg-IFN-α plus ribavirin (RBV) therapy. Case 1: a 48-year-old male with chronic hepatitis C with chronic thyroiditis. The patient's plasma glucose level was normal and anti-islet autoantibody tests were negative before Peg-IFN-α+RBV therapy. The emergence of glutamic acid decarboxylase 65 autoantibody (GAD65Ab) was observed after five months of treatment. Autoantibodies to insulin and insulinoma-associated antigen-2 (IA-2) also became positive. Eleven months later, thirst and polydipsia occurred with increased fasting plasma glucose level and the patient was diagnosed with type 1A diabetes. Zinc transporter-8 autoantibody (ZnT8Ab) was not detectable at any point. The patient has type 1 diabetes-susceptible HLA-DRB1-DQB1 haplotypes *0405-*0401 and *0901-*0303. Case 2: a 65-year-old male with chronic hepatitis C with type 2 diabetes on insulin treatment. GAD65Ab and IA-2Ab were negative before Peg-IFN-α+RBV therapy, however, nine months later, a single appearance of GAD65Ab was observed. After twelve months, his plasma glucose control worsened rapidly, and he was diagnosed with type 1A diabetes. IA-2Ab and ZnT8Ab were negative throughout the clinical course. His HLA-DRB1-DQB1 haplotypes were *0410-*0402 and *1407-*0503. Both cases showed a unique GAD65Ab epitope (amino acids 360-442). These clinical courses suggest that IFN-α therapy provoked acute islet autoimmunity and onset of type 1 diabetes. Therefore, during IFN-α therapy, patients should be closely monitored for the occurrence of type 1 diabetes.
Nakamura
Kan
K
Department of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, Japan.
Kawasaki
Eiji
E
Abiru
Norio
N
Jo
Ozora
O
Fukushima
Keiko
K
Satoh
Tsuyoshi
T
Kuriya
Genpei
G
Kobayashi
Masakazu
M
Kuwahara
Hironaga
H
Yamasaki
Hironori
H
Ide
Tatsuya
T
Eguchi
Katsumi
K
D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D027682:Cation Transport Proteins / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced* / Q000276:immunology*; D005968:Glutamate Decarboxylase / Q000276:immunology; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D000075703:Zinc Transporter 8
D001323:Autoantibodies; D027682:Cation Transport Proteins; D016898:Interferon-alpha; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2