Hepatitis C virus infection and development of type 2 diabetes mellitus: Systematic review and meta-analysis of the literature

Type 2 diabetes mellitus (T2DM) is an endocrine disorder encompassing multifactorial mechanisms, and chronic hepatitis C virus infection (CHC) is a multifaceted disorder, associated with extrahepatic manifestations, including endocrinological disorders. CHC and T2DM are associated, but the subject remains controversial. We performed a systematic review and meta-analysis evaluating such association, searching on PubMed until February 29, 2016. Inclusion criteria were: 1) presence of at least one internal control group age- and gender-matched (non-hepatopathic controls; and/or hepatopathic, not HCV-positive, controls); 2) sufficient data to calculate odds ratio and relative risk. Exclusion criteria were: 1) literature reviews on the topic; 2) publications regarding special populations [human immunodeficiency virus and human T-lymphotropic virus-1 coinfections, hepatocellular carcinoma (HCC), post-transplantation DM, gender selection]; 3) no clear differentiation among HCV patients with CHC, cirrhosis or HCC. Data from each study were independently extracted by two reviewers and cross-checked by AA. Our systematic review returned 544 records, and 33 were included in our meta-analysis. HCV infection is associated with an increased risk of T2DM independently from the severity of the associated liver disease, in CHC and cirrhotic HCV patients. As expected T2DM risk is higher in cirrhotic HCV patients, than CHC, and the prevalence of HCV infection in T2DM patients is higher than in non-diabetic controls. Regarding HBV infection prevalence, no difference exists in diabetic and non-diabetic subjects. An unequivocal CHC and T2DM association was shown. A proactive, integrated approach to HCV and T2DM therapies should maximize benefits of both diseases treatment.