Traditional Chinese Medicine in Chronic Hepatitis B: Integrating Antiviral Effects and Immune Modulation in the Context of T Cell Exhaustion.

Authors

Xinyu Zhao, Chunfeng Mei, Fan-E Cheng, Size Li, Shihao Zheng, Wenying Qi, Yongan Ye

Published in

Drug design, development and therapy. Volume 20. Pages 623907. Epub Aug 11, 2026.

Abstract

Chronic hepatitis B (CHB) remains a major global health burden because nucleos(t)ide analogues (NAs), although highly effective in suppressing viral replication, rarely achieve functional cure. A central barrier is the exhaustion of HBV-specific T cells, a multilayered state driven by persistent antigen exposure, inhibitory receptor signaling, mitochondrial and metabolic dysfunction, transcriptional and epigenetic fixation, and the tolerogenic hepatic microenvironment. Single-target checkpoint blockade, effective in oncology, is limited in CHB by redundant inhibitory networks, providing a rationale for multi-target strategies. Traditional Chinese medicine (TCM), characterized by multicomponent and multitarget pharmacology, has been widely used as an adjunctive strategy in CHB, but its relationship to antiviral immunity remains incompletely defined. This review synthesizes mechanistic, preclinical, and clinical evidence on TCM-derived phytochemicals and compound formulas in the context of HBV-specific T cell exhaustion. The novelty of this review lies in using T cell exhaustion as the organizing framework to distinguish five mechanistic axes of TCM action: reduction of viral antigen burden, modulation of checkpoint and costimulatory pathways, restoration of metabolic fitness, regulation of transcriptional or epigenetic programs, and remodeling of the hepatic immune microenvironment. Current evidence suggests that many TCM-related benefits are more readily explained by suppression of HBV replication and indirect reduction of antigen-driven T cell dysfunction than by definitive T cell-intrinsic reprogramming. Clinical studies indicate that TCM combined with NAs may improve virological, biochemical, and serological outcomes, including HBeAg seroconversion and HBsAg decline, but functional cure rates remain limited and immunological endpoints are rarely assessed. Key challenges include mechanistic ambiguity, variable formulation quality, pharmacokinetic uncertainty, and region-specific clinical evidence. Future biomarker-driven studies integrating standardized formulations, pharmacokinetic validation, and HBV-specific T cell profiling are needed to establish whether, and under what conditions, TCM can contribute to durable immune control and functional cure in CHB.

PMID:
42609479
Bibliographic data and abstract were imported from PubMed on 18 Aug 2026.

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