Biomarkers and Mechanistic Insights Linking Functional Cure, Disease Progression, and Hepatocarcinogenesis in Chronic Hepatitis B Toward Precision Medicine

Chronic hepatitis B virus (HBV) infection remains a major global health challenge, as many patients continue to face cirrhosis, hepatocellular carcinoma, and liver-related mortality despite effective antiviral suppression. Functional cure, generally defined by sustained hepatitis B surface antigen (HBsAg) loss with or without seroconversion, is an important therapeutic goal but is achieved in only a minority of treated individuals. Current research is addressing critical questions regarding the determinants of HBsAg decline and loss, the restoration of antiviral immunity, and the durability of viral control. Evidence from large clinical cohorts, real-world studies, immune-profiling analyses, single-cell technologies, multi-omics investigations, and experimental models has revealed complex interactions among viral reservoirs, host immunity, treatment exposure, and disease stage. Recent advances in multi-omics technologies have further expanded opportunities to identify molecular biomarkers associated with disease progression, treatment response, and hepatocarcinogenesis, providing new insights into precision medicine for chronic HBV infection. Nevertheless, the predictive value of many candidate biomarkers remains inconsistent, and the molecular mechanisms that distinguish functional cure from transient treatment response are not fully understood. Integrating clinical observations with mechanistic evidence is therefore essential for improving outcome prediction and advancing personalized approaches.This Research Topic aims to define the clinical, virological, immunological, and molecular factors associated with functional cure in chronic hepatitis B. It seeks to identify and validate biomarkers that can predict HBsAg decline, HBsAg loss, treatment response, and durable viral control; clarify the mechanisms underlying immune restoration and host–virus interactions; and evaluate how these insights can guide treatment selection, response monitoring, and the development of novel therapeutic strategies. Studies may also address whether integrated clinical and multi-omics models can improve patient stratification and support precision medicine. Studies integrating clinical cohorts with multi-omics approaches to investigate biomarkers, disease progression, hepatocarcinogenesis, and precision medicine in HBV-related liver diseases are also encouraged. By connecting clinical data with mechanistic discoveries, this Research Topic aims to accelerate the development of interventions that increase functional cure rates.To gather further insights into biomarkers, mechanisms, prediction, and therapeutic strategies for functional cure in chronic hepatitis B, we welcome articles addressing, but not limited to, the following themes:o Clinical cohort studies and real-world evidence on predictors of HBsAg decline, HBsAg loss, seroconversion, and treatment responseo Virological, immunological, molecular, and multi-omics biomarkers of functional cureo Validation, standardization, and clinical implementation of predictive biomarkerso Host–virus interactions and the biology of covalently closed circular DNA and viral antigen persistenceo Innate and adaptive immune regulation, including T-cell, B-cell, natural killer cell, and myeloid-cell responseso Mechanisms of immune exhaustion, immune restoration, and durable viral controlo Single-cell, spatial, transcriptomic, proteomic, metabolomic, and epigenetic approacheso Experimental models for investigating HBV persistence and functional cureo Novel antiviral, immunomodulatory, and combination treatment strategieso Predictive models, risk stratification, and precision therapeutic approacheso Multi-omics studies for biomarker discovery, disease progression, hepatocarcinogenesis, and precision medicine in HBV-related liver diseasesConflicts of Interest declaration: Dr. Xiaofeng Huang is a full-time employee of Johnson & Johnson Topic editors: Xin Wang, Xiaofeng Huang, Hao Liao Source: https://www.frontiersin.org/research-topics/85373/biomarkers-and-mechanistic-insights-linking-functional-cure-disease-progression-and-hepatocarcinogenesis-in-chronic-hepatitis-b-toward-precision-medicine