Hepatitis C in the Direct-Acting Antiviral Era: Immunopathogenesis, Dendritic Cells and Modern Clinical Management

Hepatitis C virus (HCV) infection remains a major cause of chronic liver disease worldwide, with potential progression to advanced fibrosis, cirrhosis, hepatocellular carcinoma, and extrahepatic disease. According to World Health Organization estimates, approximately 50 million people worldwide live with chronic HCV infection, and nearly 1 million new infections occur each year. In 2022, approximately 242,000 deaths were attributed to hepatitis C, mainly from cirrhosis and hepatocellular carcinoma. Chronic infection develops when antiviral immune response fails to eliminate the virus. Viral clearance requires early innate immune activation, effective antigen presentation, broad HCV-specific CD4+ and CD8+ T-cell responses and durable immune memory. Dendritic cells play a pivotal role in this process by linking innate and adaptive immunity. In chronic HCV infection, dendritic cells may be reduced in number and show impaired maturation, lower interleukin (IL)-12 production, higher IL-10 expression and weaker stimulation of HCV-specific CD4+ T-cell responses. This review discusses the role of dendritic cells (DCs) in HCV infection, with emphasis on DCs’ phenotype and function in acute and chronic disease. It also summarizes immune changes after direct-acting antiviral (DAA)-induced sustained virologic response (SVR), including partial recovery of innate immune responses and persistent residual immune dysregulation. When accessible and appropriately selected, modern direct-acting antiviral therapy substantially improves outcomes for patients with HCV infection.