Onset of Type 1 Diabetes Mellitus During Pegylated-interferon Alfa and Ribavirin Therapy for Chronic Hepatitis C Virus Infection

Abstract

P egylated-interferon (PEG-IFN) alfa (α) in combination with ribavirin is the approved treatment for chronic hepatitis C virus (HCV) infection. Since the first report of interferon (IFN)-induced type 1 diabetes mellitus (DM) in 1992 by Fabris et al, 1 there have been numerous reports from all over the world. Interferon in combination with ribavirin induces type 1 diabetes in a much shorter period compared with plain IFN.2 Interferoninduced diabetes has not been reported from India till date. Here we report PEG-IFN-induced type 1 DM in a 16-year-old, who was on treatment for chronic HCV infection with PEG-IFN 2b and ribavirin. CASE REPORTA 16-year-old female who had undergone treatment for Ewing's sarcoma with right cleidectomy and chemotherapy turned seropositive for HCV (genotype 1 infection) at the end of the chemotherapy. She had raised HCV-RNA and was started on combination therapy with ribavirin 800 mg orally daily and plain IFN-α-2b 3MIU subcutaneously (SC) thrice weekly and completed 78 doses of the same. She did not respond to plain IFN and was switched over to PEG-IFN-α-2b 50 μg SC weekly and ribavirin 800 mg orally daily combination therapy. There was no history of diabetes or other autoimmune diseases in her family members. Her weight was 46 Kg and her body mass index (BMI) was 21.9 Kg/m 2 . Complete blood count showed a total leukocyte count of 4900/mm 3 , hemoglobin of 10.8 g/dL, and platelet count of 289,000/mm 3 . Biochemical investigations revealed random blood sugar 106 mg/dL, normal serum bilirubin, albumin 4.7, serum glutamicpyruvic transaminase (SGPT) 44 U/L, and normal thyroid functions. Ultrasound abdomen showed normal sized liver with coarse echotexture and normal portal vein. No varices were seen on endoscopy. She attained a rapid virological response. Except for mild anemia, a period of 40 weeks of the combination therapy was uneventful.She presented with features of severe ketoacidosis following the 41st dose of PEG-IFN. She gave a history of polyuria, polydipsia, and weight loss for < 2 weeks. She had a random blood sugar of 431 mg/dL, with severe metabolic acidosis and urine ketone positivity. Her ketoacidosis was managed with intravenous (i.v.) insulin infusion and fluid replacement. She was discharged on regular subcutaneous insulin. Anti-glutamic acid decarboxylase (anti-GAD) antibodies and islet cell antibodies (ICA) were negative and her fasting serum C-peptide level was <0.1 ng/ mL. Based on the clinical presentation and low C-peptide level, she was diagnosed with type 1 DM.While there have been case reports endorsing the cessation of the IFN therapy after the onset of diabetes, our patient had a low C-peptide level indicating that majority of the islet cells were destroyed by then. The risk of worsening of diabetes due to HCV-induced insulin resistance, in the absence of a sustained virological response, 3 outweighed the risks of worsening of type 1 DM due to further beta cell destruction with continuation of IFN. Hence, PEG-IFN and ribavirin were continued. Her HCV-RNA load at...

Characteristics of Interferon-Associated Diabetes Mellitus in Past 30 Years: A Review

“…Patients were evaluated for clinical characteristics such as age, sex, IFN type, ribavirin use, treatment duration of IFN before the onset of diabetes, HLA type, and glutamate decarboxylase antibody-positive rate. We retrieved 82 cases of IFN-associated diabetes, including 1 case of our own (Supplementary Material 2) 4 5 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 . According to the consensus report by the ADA and the EASD 57 , we identified all IFN-associated type 1 diabetes cases.…”

Association between hepatitis C antiviral treatment and diabetes mellitus: A case series

“…Interferon therapy for HCV has been associated with T1DM in rare case reports (22,32,33). Studies in Japan have demonstrated that the mean onset of T1DM after initiation of interferon therapy was approximately 0.7 years, with the majority of patients experiencing a fulminant, sudden-onset form of the disease (34).…”