No abstract

Hepatitis C virus (HCV) infection is associated with insulin resistance (IR), which is a condition known to influence the progression of liver fibrosis and the response to pegylated interferon (PEG-IFN)/ribavirin (RBV) therapy. We aimed to assess whether a sustained virological response (SVR) after antiviral therapy prevents the development of IR in the long term. Members of the Milan Safety Tolerability study cohort, who received PEGIFNa2a/RBV or PEG-IFNa2b/RBV, underwent a homeostasis model assessment (HOMA) at the baseline and 24 months after treatment completion. For all patients (n 5 431), a liver biopsy sample was scored for grading, staging (Ishak), and steatosis. At the baseline, IR (HOMA value > 2) was detected in 48 patients (12%), and it was associated with body weight (P 5 0.03), an HCV load < 0.6 3 10 6 IU/L (P 5 0.006), fibrosis staging ! 4 (P 5 0.01), and moderate to severe steatosis (P 5 0.03). IR did not influence the rates of endof-treatment response (75% versus 69%, P 5 0.4), SVR (63% versus 60%, P 5 0.8), or relapse (19% versus 24%, P 5 0.5). After treatment, IR developed in 49 of the 384 nondiabetic patients (14%). Although the mean baseline and posttreatment HOMA values were similar in SVR patients (1.11 6 0.8 versus 1.18 6 1.1, P 5 0.25), patients experiencing treatment failure showed a significant increase in the mean HOMA value at the followup visit (1.20 6 0.85 versus 1.49 6 1.3, P 5 0.007), and there was an increased rate of de novo IR in non-SVR patients versus SVR patients (17% versus 7%, P 5 0.007). According to a logistic regression analysis, treatment failure (odds ratio 5 2.81, 95% confidence interval 5 1.39-5.67, P 5 0.004) and a 10% body mass index increase (odds ratio 5 6.42, 95% confidence interval 5 1.69-24.3, P 5 0.006) were significantly associated with the development of de novo IR. Conclusion: In nondiabetic patients with chronic HCV, the achievement of SVR with PEG-IFN and RBV prevents the development of de novo IR.

By definition, hepatogenous diabetes is directly caused by loss of liver function, implying that it develops after cirrhosis onset. Therefore, it should be distinguished from type 2 diabetes developing before cirrhosis onset, in which specific causes of liver disease play a major role, in addition to traditional risk factors. Currently, although hepatogenous diabetes shows distinct pathophysiological and clinical features, it is not considered as an autonomous entity. Recent evidence suggests that the failing liver exerts an independent "toxic" effect on pancreatic islets resulting in β-cell dysfunction. Moreover, patients with hepatogenous diabetes usually present with normal fasting glucose and haemoglobin A levels and abnormal response to an oral glucose tolerance test, which is therefore required for diagnosis. This article discusses the need to separate hepatogenous diabetes from type 2 diabetes occurring in subjects with chronic liver disease and to identify individuals suffering from this condition for prognostic and therapeutic purposes.