Hepatitis C Virus and Type 2 Diabetes: Mechanisms, Clinical Impact, and Post-DAA Management

Hepatitis C virus (HCV) infection remains a major global health burden despite advances in direct-acting antiviral (DAA) therapies. Beyond hepatic complications such as cirrhosis and hepatocellular carcinoma (HCC), HCV has been strongly linked to metabolic disorders, particularly type 2 diabetes mellitus (T2DM). Epidemiological evidence demonstrates a higher prevalence of diabetes among HCV-infected individuals, with variations across geographic regions and populations. Mechanistically, HCV induces insulin resistance (IR) through multiple pathways, including direct interference of viral proteins with insulin signaling, oxidative stress, cytokine imbalance, impaired lipid metabolism, and pancreatic β-cell dysfunction. T2DM further worsens HCV outcomes by accelerating fibrosis, increasing the risk of HCC, and elevating all-cause mortality. Importantly, clearance of HCV with DAAs improves IR, reduces diabetes incidence, and lowers cardiovascular risks. Integrated prevention and management strategies targeting both viral eradication and glycemic control are essential to optimize outcomes. This review aims to bridge mechanistic insights with clinical evidence, facilitating strategies that improve outcomes in HCV-associated metabolic disease.