Hepatic Macrophages and Immune Injury in Chronic Viral Hepatitis

Abstract

Chronic viral hepatitis remains a major cause of persistent liver inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma, with hepatic macrophages playing a central role in regulating both antiviral immunity and tissue injury. These macrophages comprise resident Kupffer cells and monocyte-derived macrophages that are dynamically recruited and functionally reprogrammed during persistent viral infection. Their responses are shaped by viral components, damaged hepatocytes, inflammatory cytokines, chemokines, and signals derived from the hepatic microenvironment. During chronic hepatitis B and hepatitis C virus infections, macrophages can contribute to antiviral defense through antigen presentation, cytokine production, and activation of innate immune pathways. However, prolonged or dysregulated macrophage activation may promote immune-mediated hepatocyte damage, oxidative stress, inflammatory signaling, and extracellular matrix deposition. The balance between inflammatory and reparative macrophage phenotypes therefore strongly influences disease progression and hepatic tissue remodeling. Macrophage-derived mediators, including tumor necrosis factor-α, interleukin-1β, interleukin-6, transforming growth factor-β, and chemokines, can amplify interactions between innate and adaptive immune cells and sustain chronic hepatic inflammation. Conversely, regulatory macrophage populations may suppress excessive immune responses and facilitate tissue repair, although persistent viral infection can disrupt these protective functions. Understanding the mechanisms governing macrophage recruitment, polarization, metabolic reprogramming, and communication with hepatocytes, stellate cells, and lymphocytes is essential for clarifying the pathogenesis of chronic viral hepatitis. This review highlights the multifaceted contribution of hepatic macrophages to immune injury, inflammatory persistence, fibrosis, and disease progression.