Metabolic Effects of Direct-Acting Antiviral Therapy in Chronic Hepatitis C: A Focus on Glucose and Lipid Profiles

Abstract Hepatitis C virus (HCV) infection is a leading global cause of chronic liver disease and is increasingly recognized for its extrahepatic metabolic consequences, particularly in lipid and glucose homeostasis. The introduction of direct-acting antiviral agents (DAAs) has revolutionized HCV therapy, enabling high sustained virological response (SVR) rates. However, the metabolic impact of viral eradication remains incompletely understood. This study aimed to evaluate changes in fasting lipid and glycemic parameters following successful DAA therapy. A single-center, retrospective observational study was conducted at La Rabta Hospital (Tunis), including 49 consecutive patients with chronic hepatitis C who received DAA therapy between 2016 and 2022 and achieved SVR at both 12 and 48 weeks post-treatment. Patients with confounding metabolic or hepatic comorbidities were excluded. Fasting glucose, total cholesterol, triglycerides, HDL-cholesterol, and LDL-cholesterol levels were compared before and after antiviral therapy. Post-treatment, a statistically significant reduction in mean fasting glucose was observed (6.1 ± 2.1 to 5.8 ± 1.9 mmol/L; p = 0.048), alongside a significant increase in total cholesterol (3.8 ± 0.8 to 4.1 ± 0.9 mmol/L; p = 0.015). Changes in triglycerides, HDL-C, and LDL-C were not statistically significant. These findings suggest that HCV eradication via DAA therapy may improve glycemic control and an increase total cholesterol. Routine metabolic surveillance post-SVR is advisable, particularly in patients with elevated cardiovascular risk. Further prospective studies are warranted to elucidate the long-term clinical implications.