Pregenomic RNA as a Marker for Monitoring Disease Prognosis and Viral Relapse in Hepatitis B Patients on Long‐Term Antiviral Therapy: A Systematic Review and Meta‐Analysis

Chronic hepatitis B virus (HBV) infection poses a significant global health burden, with long‐term antiviral therapy being the primary treatment. However, predicting disease progression and the risk of viral relapse after treatment cessation remains difficult. Serum HBV pregenomic RNA (pgRNA) has recently gained attention as a potential biomarker reflecting intrahepatic viral activity, particularly that of covalently closed circular DNA (cccDNA). This study aimed to evaluate pgRNA's clinical utility as a prognostic marker in chronic HBV (CHB) patients on long‐term therapy. A systematic literature review was conducted using PubMed and Scopus, including studies up to August 27, 2024. Selected studies assessed pgRNA in relation to disease prognosis, treatment response, and relapse. Meta‐analysis showed a significant reduction in pgRNA levels post‐treatment (mean difference: 1.64; 95% CI: 0.79–2.49), consistent with decreases in HBV DNA and HBsAg. These findings support pgRNA may serve as a promising surrogate marker for treatment prognosis and potential viral relapse in HBV patients.