# Accuracy of Diagnostic Investigations in Monitoring Hepatitis B Virus Infection: Strengths, Limitations, and Emerging Biomarkers

## TL;DR

This paper reviews current and emerging biomarkers for monitoring hepatitis B virus infection and highlights their potential for improving treatment decisions and outcomes.

## Contribution

The study identifies and evaluates new biomarkers like HBcrAg, serum HBV RNA, and qAnti-HBc for improved monitoring and treatment of HBV.

## Key findings

- HBcrAg correlates with cccDNA activity and virological rebound after treatment.
- Serum HBV RNA provides insights into transcriptional activity relevant for RNA-targeted therapies.
- Quantitative anti-HBc is linked to stronger immune memory and fewer ALT flares.

## Abstract

In October 2020, the International Coalition to Eliminate Hepatitis B Virus (ICE-HBV) updated the biomarker framework; they underscored major advances in the understanding of viral and immunologic markers, yet highlighted persistent gaps in their clinical integration. This is particularly the case in low- and middle-income regions, where HBV remains a substantial public health problem, including in the pediatric population. To synthesize contemporary evidence, a structured literature search was performed across PubMed/MEDLINE, Scopus, and Web of Science. Classical biomarkers—including HBeAg, HBV DNA, and quantitative HBsAg—remain central for disease staging and therapeutic monitoring, while emerging markers enhance precision in risk stratification: HBcrAg, which correlates strongly with intrahepatic cccDNA activity and virological rebound after NA discontinuation; serum HBV RNA, which offers additional insight into transcriptional activity, which is particularly relevant for RNA-targeted therapies; and quantitative anti-HBc (qAnti-HBc), which reflects stronger humoral imprinting and more competent HBV-specific immune memory, and is consistently associated with fewer ALT flares and reduced virological rebound at end of treatment. Despite these advances, assay standardization, genotype-related variability, and limited pediatric data constrain broad clinical application. Integrating classical and emerging biomarkers into personalized therapeutic algorithms offers substantial potential for refining treatment decisions, predicting post-treatment outcomes, and advancing HBV elimination strategies in diverse clinical settings.