AUTHOR=Zhu Hanxu , Zhang Feng , Tian Zhezhe , Xu Miaomiao , Fan Yuchen , Gao Shuai , Wang Kai TITLE=Hypermethylation of Ring finger protein 41 promoter is associated with early hepatitis B virus-related cirrhosis JOURNAL=Frontiers in Medicine VOLUME=Volume 12 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1631990 DOI=10.3389/fmed.2025.1631990 ISSN=2296-858X ABSTRACT=ObjectivesNew biomarkers are needed to detect liver cirrhosis at an earlier stage and to individualize treatment strategies. This study specifically investigates the diagnostic potential of Ring finger protein 41 promoter methylation as an epigenetic biomarker for detecting early-stage hepatitis B virus-related liver cirrhosis.MethodsThe methylation level of the Ring finger protein 41 promoter in peripheral blood mononuclear cells of 190 participants were quantified with Methylight, and the changes of serum inflammatory cytokines related to liver fibrosis were analyzed simultaneously.ResultsPatients with early-stage liver cirrhosis exhibited significantly higher methylation levels of Ring finger protein 41 promoter than chronic hepatitis B patients and health controls, accompanied by reduced mRNA expression. Remarkably, the receiver operating characteristic analysis demonstrated that Ring finger protein 41 promoter methylation achieved a superior diagnostic performance (area under the curve) for distinguishing hepatitis B virus-related compensated liver cirrhosis, outperforming conventional non-invasive indicators including liver stiffness measurement, aspartate aminotransferase-to-platelet ratio index, and fibrosis-4 score.ConclusionRing finger protein 41 may play a critical role in the pathogenesis of liver cirrhosis, with its methylation status in peripheral blood mononuclear cells demonstrating strong potential as a non-invasive biomarker for early liver cirrhosis detection.