Are metabolic factors still important in the era of direct antiviral agents in patients with chronic hepatitis C?

Abstract

The high rate of sustained viral response (SVR) to boceprevir or telaprevir-based triple therapy in hepatitis C (HCV)-related, non-cirrhotic naïve patients or relapsers to previous antiviral treatment leads clinicians to believe that the impact of metabolic host factors on SVR is minimal when triple therapy is used, unlike what is observed with the peginterferon and ribavirin schedules. This concept is strongly expressed by some opinion leaders on the basis of the data derived from sub-analyses of registrative trials as well as from a post-hoc analysis of the phase II C208 clinical trial. The perception of unrestrainable therapeutic success with the use of newer, more powerful antivirals is now reinforced by the brilliant results obtained with sofosbuvir, an HCV NS5B polymerase inhibitor, as well as by the data from the phase II and III studies on the various combinations of second-generation NS3/4A inhibitors and NS5A and/or NS5B inhibitors. However, a great deal of concern has emerged from the real world scenario in which patients are often older and have more comorbidities than patients in the “world of trials”. Furthermore, many of them have advanced fibrosis and previous failure with peginterferon and ribavirin treatment. Some data from the recent literature suggest that the host metabolic factors may play a minor but non-negligible role in these difficult-to-treat patients, an issue that will hopefully be investigated in further studies. This editorial aims to provide a detailed analysis of the role that host metabolic factors played in the past and what role they may play in the era of direct antiviral agents.

Keywords: Metabolic factors, Insulin resistance, Direct antiviral agents, Chronic hepatitis C

Core tip: This editorial explores the past and present role of metabolic factors by analyzing the data that has emerged from the post hoc analysis of registrative trials of direct antiviral-based treatment. Low-density lipoprotein-cholesterol and statin use proved to be predictors of sustained viral response (SVR) in both boceprevir and telaprevir-treated patients, respectively. Furthermore, HOMA-IR negatively influenced SVR in prior partial and null responders treated with telaprevir-based schedules. By transferring these data to the real world scenario in which patients have comorbidities, advanced fibrosis and prior failure to antiviral treatment, we believe that metabolic factors might play a non-negligible role in influencing antiviral response, even in triple therapy.