Hepatitis C Direct Acting Antivirals and Ribavirin Modify Lipid but not Glucose Parameters

Abstract

Chronic hepatitis C (HCV) infection perturbs lipid and glucose metabolism. The influence of direct acting antiviral (DAA) treatment and ribavirin on these measures was evaluated. Furthermore, the effect of HCV cure on these parameters was assessed. Participants were allocated to one of three 12-week treatment groups: non-cirrhotic genotype 1a-paritaprevir/ritonavir/ombitasvir/dasabuvir (PrOD) plus ribavirin; non-cirrhotic 1b-PrOD; compensated cirrhotic 1a or 1b-PrOD plus ribavirin. Fasting insulin, glucose, lipid and apolipoprotein measures were assessed at baseline, Treatment Weeks 4 and 12, and 12 and 24 weeks post-dosing. Twenty-three of 24 participants achieved SVR (PP= 23/24, 96% SVR). Overall, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride levels all increased in treatment and post-dosing. However, LDL-C levels decreased during treatment in ribavirin recipients. Fasting glucose, insulin, and HOMA-IR were unchanged during treatment and 12 weeks post-treatment. By 12 weeks post-treatment, controlled attenuation parameter (CAP) scores, a measure of steatosis, increased from baseline (mean 30.3 ± 63.5, p = 0.05). This regimen was safe and highly effective and did not influence glucose metabolism. Ribavirin exposure may mitigate some on-treatment lipid changes. Further mechanistic studies are needed to understand how ribavirin impacts lipid pathways, as there could be therapeutic implications. The metabolic pathophysiology of increased CAP score with HCV treatment requires explanation.