# Hepatic Macrophages in Chronic Hepatitis B: Balancing Immunity and Pathology

## TL;DR

This paper explores how hepatitis B virus manipulates liver macrophages to suppress immunity and cause liver damage, suggesting new therapies that target these immune cells.

## Contribution

The paper provides a comprehensive review of how HBV alters macrophage function and explores novel therapeutic strategies to restore immune balance.

## Key findings

- HBV induces macrophages to adopt an anti-inflammatory M2-like state, suppressing antiviral immunity.
- Macrophage polarization toward an immunosuppressive phenotype promotes viral persistence and liver fibrosis.
- Targeting macrophage function with TLR agonists and immune checkpoint inhibitors is a promising therapeutic approach.

## Abstract

Hepatitis B virus (HBV) is a DNA virus that infects liver cells (hepatocytes) and can cause both acute and chronic hepatitis. In chronic infection, HBV interacts not only with liver-resident macrophages (Kupffer cells) but also with blood-derived monocytes that infiltrate the liver. The virus alters their immune function, prompting them to shift toward an anti-inflammatory, M2-like state that suppresses antiviral responses. This shift allows HBV to persist and promotes liver inflammation, fibrosis, and disease progression. Understanding how HBV manipulates Kupffer cells and monocyte-derived macrophages (MDMs) is key to developing therapies that restore immune balance. Targeting macrophage polarization represents a promising strategy to reduce viral persistence and liver injury in chronic HBV.

Chronic HBV infection remains a global health challenge, driving liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Liver injury is primarily mediated by host immune responses rather than direct viral cytotoxicity. Macrophages, including Kupffer cells, play dual roles in antiviral defense and disease progression. HBV skews macrophages toward an M2-like, immunosuppressive phenotype, promoting viral persistence and fibrogenesis via cytokines such as Interleukin (IL)-10 and Transforming growth factor-beta (TGF-β). Therapeutic strategies targeting macrophage polarization, including Toll-like receptor (TLR) agonists, immune checkpoint inhibitors, and nanoparticle-based systems, are under investigation. Addressing macrophage heterogeneity and the immunosuppressive hepatic microenvironment using advanced models is essential. Modulating macrophages offers a promising avenue to control HBV, restore immune balance, and mitigate liver injury. This review highlights the central role of macrophages in chronic HBV infection and explores emerging therapeutic strategies.