Insulin resistance (IR)-impaired SVR rate in patients with hepatitis C treated with pegylated interferon (Peg-IFN) and ribavirin (RBV)[1, 2] and the selleck chemicals clearance of the hepatitis C virus (HCV) was associated with decreased risk of metabolic abnormalities and diabetes mellitus (DM) during follow-up.[3, 4] Furthermore, HCV interacts with the insulin-signaling pathway promoting IR subsequent to interaction with protein kinase B (Akt), with the mTOR (mammalian target of rapamycin)/FKBP12-rapamycin-associated protein pathway, and with peroxisome proliferator-activator receptor gamma. These interactions may be modulated by suppressor of cytokines-3 (SOC-3),

tumor necrosis factor alpha (TNF-α), and protein-tyrosine phosphatase (PTP1B).[5, 6] PTP1B was down-regulated in infected cells treated with metformin,[7] and, when inhibited with pervanadate or knocking down PTP-1B, selleck chemicals llc IFN-α response in vitro was restored.[8] Despite the wealth of molecular, clinical, and epidemiological knowledge, IR modulation did not become a priority in the management of hepatitis C in standard clinical practice. This could be a result, at least in part, of the lack of effect of adding metformin[9] or pioglitazone[10] to Peg-IFN and RBV in patients infected by genotype 1. Insulin sensitizers did not increase SVR significantly,

despite improvement in insulin sensitivity. In the hepatitis C setting, IR appears to result from the sum of viral-induced and host-related IR. Danoprevir in monotherapy (excluding bias related to Peg-IFN use) has been found to improve insulin sensitivity in parallel with HCV RNA decline after 2 weeks of therapy.[11] Last, a recent meta-analysis showed several key aspects influencing the relationship between homeostasis model assessment for IR (HOMA-IR) and SVR: (1) selection and interaction between covariables.

medchemexpress HOMA-IR showed a strong colinearity with variables such as steatosis or obesity, but also with gamma-glutamyl transpeptidase levels, triglyceride levels, age, and fibrosis[12]; (2) baseline biochemical characteristics of the cohort studied. The higher the baseline HOMA-IR, the better the HOMA-IR prediction; and (3) SVR rate; in easy-to-cure patients, such as those with mild fibrosis or those infected by genotype 2, or in patients with higher expected SVR such as those receiving potent antiviral agents, HOMA-IR would show less or null influence on SVR. In the current issue of HEPATOLOGY, Younossi et al.[13] report on a negative post-hoc study of the effect of IR (measured by HOMA-IR) on SVR in genotype 1 patients who, previously, had failed with Peg-IFN and RBV, including relapsers, partial responders, and null responders.