Chronic Hepatitis C Virus Infection Is Associated with an Increased Risk of Diabetes Mellitus in Thalassemia Major

Introduction. Hepatitis C virus (HCV) infection is associated with a number of important extrahepatic manifestations. The association between HCV infection and the occurrence of diabetes mellitus remains controversial.

Aim. The aim of this multicentric study was to prospectively assess the relationship between HCV infection and diabetes mellitus in patients with thalassemia major (TM).

Methods. We considered 1057 TM patients (539 females; 29.79±10.08 years) consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT). Every 18±3 months the patients performed a magnetic resonance imaging (MRI) scan for iron overload assessment by the T2* technique. The disturbances of glucose metabolism were assessed within three months from each MRI by means of oral glucose tolerance test (OGTT).

Results. On the basis of the presence of HCV antibodies and RNA, a categorization in 4 groups was performed: negative patients (group 1a, N=460), patients who spontaneously cleared the virus in the first 6 months of infection (group 1b, N=242), patients who eradicated the virus after the treatment with antiviral therapy obtaining a sustained virological response (SVR) (group 2, N=102), and patients with chronic HCV infection (group 3, N=254). The absolute first MRI was the baseline for patients in groups 1a, 1b and 3 while for patients in group 2 the baseline was represented by the first MRI performed after the virus eradication. The follow-up date coincided with the date of the last available MRI.

Mean age was significantly lower in group 1a than in all the other 3 groups and in both groups 1b and 3 than in group 2. Group 1a and 1b were considered as a unique group (group 1, no chronic HCV infection). A match 1:1 for age and sex with group 2 was performed.

At the baseline ALT and AST levels were significantly increased in group 3 versus both groups 1 and 2 (P<0.0001 for all comparison) and GGT was significantly higher in group 3 than in group 2 (P=0.024). No significant difference was detected in iron overload indices. The OGTT was not performed in 5 patients without known diabetes and frequency of diabetes was comparable among the three groups.

Mean follow-up time was 66.27±39.23 months. Among the 253 (84.1%) patients free of diabetes at the baseline MRI, 8 did not perform the OGTT at the follow-up. So, we considered 245 patients: 85 in group 1, 83 in group 2, and 77 in group 3. During the follow-up, diabetes mellitus was recorded in the 2.4%, 6.0% and 7.8% of patients in group 1, 2 and 3, respectively. The chronic HCV group showed a significantly higher risk of diabetes than group 1 (hazard-ratio-HR=5.33, 95%CI=1.06-26.93; P=0.043). The Figure shows the Kaplan-Meier curve.

Conclusion. Chronic HCV infection is associated with a significant higher risk of diabetes mellitus in TM patients and, as a consequence, it should be analyzed as a systemic disease in which extrahepatic consequences increase the weight of its pathological burden.

Maggio:Vertex: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Celgene Corp (Bristol Meyers Squibb): Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Pepe:Bayer: Other: no profit support; Chiesi Farmaceutici S.p.A: Other: no profit support. Cademartiri:Bayer: Other: no profit support; Chiesi Farmaceutici S.p.A: Other: no profit support.