Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2015; 21(1): 233-239
Published online Jan 7, 2015. doi: 10.3748/wjg.v21.i1.233
Interferon therapy in hepatitis C leading to chronic type 1 diabetes
Taiba Zornitzki, Stephen Malnick, Lyudmila Lysyy, Hilla Knobler
Taiba Zornitzki, Lyudmila Lysyy, Hilla Knobler, Department of Diabetes, Metabolism and Endocrinology, Hebrew University Medical School, Kaplan Medical Center, Rehovot 76100, Israel
Stephen Malnick, Department of Gastroenterology, Hebrew University Medical School, Kaplan Medical Center, Rehovot 76100, Israel
Author contributions: Zornitzki T, Malnick S and Knobler H designed the research; Zornitzki T and Knobler H reviewed and analyzed the interferon-induced type 1 diabetes literature; Lysyy L evaluated and wrote the case report; Zornitzki T, Malnick S and Knobler H wrote the manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Stephen Malnick, MA, MSc, MBBS, Director, Department of Gastroenterology, Hebrew University Medical School, Kaplan Medical Center, HaGalil St 5, Rehovot 76100, Israel. stephen@malnick.net
Telephone: +972-8-9441852 Fax: +972-8-9441852
Received: March 28, 2014
Peer-review started: March 29, 2014
First decision: April 15, 2014
Revised: July 20, 2014
Accepted: July 24, 2014
Article in press: July 25, 2014
Published online: January 7, 2015
Processing time: 284 Days and 12.1 Hours
Abstract

AIM: To review the prevalence, clinical data and course of interferon- associated type 1 diabetes in chronic hepatitis C virus (HCV) infection.

METHODS: Search of all interferon (INF)-related type 1 diabetes mellitus (T1DM) cases published in the English literature from 1992 to December 2013 according to the key words: chronic hepatitis C infection, diabetes mellitus type 1, insulin dependent diabetes mellitus, and interferon treatment. We found 107 cases and analyzed their clinical and laboratory data and long-term follow-up. Due to the predominance of cases described in Japanese literature, we analyzed separately cases of Caucasian and Japanese origin. In addition we describe a representative case with HCV who developed INF-related T1DM.

RESULTS: Our data show that INF treatment increases the risk of developing T1DM by 10-18 fold compared with the corresponding general population and the median age of onset was 43 years (range: 24-66 years) in Caucasians and 52 years (range: 45-63 years) in Japanese. Most patients developed T1DM during INF treatment, after a median time-period of 4.2 and 5.7 mo in Caucasian and Japanese groups, respectively. The clinical course was characterized by a fulminant course with abrupt severe hyperglycemia or ketoacidosis, a high titer of anti-islet autoantibodies and almost all patients (105/107) permanently required insulin therapy with a follow-up of up to 4 years. A substantial number of patients had evidence for other autoimmune disorders mainly thyroid diseases (25% and 31% in Caucasian and Japanese groups, respectively).

CONCLUSION: INF-associated T1DM in HCV has a fulminant course, often associated with other autoimmune diseases, and results almost inevitably in permanent insulin therapy requirement.

Keywords: Interferon, Hepatitis C, Type 1 diabetes, Autoimmune diseases, Pancreatic autoantibodies

Core tip: Interferon (INF) treatment is an important component of hepatitis C virus treatment. Although INF-associated type 1 diabetes mellitus was described more than 2 decades ago its importance is under-recognized. Based on a review of all published cases we found that this complication typically appears abruptly, is manifested by severe hyperglycemia accompanied by a high titer of anti-islet antibodies and is often associated with autoimmune thyroid disease. Most worrisome, almost all patients who develop this complication require permanent insulin treatment. With the emergence of new interferon-free therapies, this serious complication has to be taken into consideration especially in relatively young patients with mild to moderate disease.