Molecular Biomarkers Associated with Inflammatory and Fibrotic Pathways in Chronic Liver Disease: A Systematic Review

Abstract

Objective: Chronic liver disease (CLD) is driven by chronic inflammation and progressive fibrosis, resulting in cirrhosis and hepatocellular carcinoma. Molecular biomarkers may enable non-invasive diagnosis, prognostication, and therapeutic targeting, but comprehensive synthesis remains limited. This systematic review aimed to evaluate the biomarkers involved in the inflammatory and fibrotic pathways in the etiology of CLD. Data Sources: Studies reporting molecular biomarkers in CLD inflammatory or fibrotic pathways were searched from January 2016 to December 2025 using PubMed, Scopus, Web of Science, and Google Scholar in accordance with PRISMA 2020 guidelines. Study Selection: Observational, cross-sectional, and preclinical experimental studies that provided therapeutic insights on inflammatory and fibrotic pathways were included, whereas reviews, editorials, and non-English articles were excluded. Data Extraction: Two reviewers extracted data independently. The Newcastle-Ottawa Scale, JBI Checklist, and SYRCLE tool were used to measure the risk of bias, and the GRADE approach was used to evaluate the quality of evidence. Data synthesis: Twelve studies were included. The most important inflammatory biomarkers identified in CLD were IL-17F (ACLF progression), IL-6/CRP (decompensated ACLD), NLRP3/CASP1 (HCV), CASP-11/4 (AH), and CK18 (NAFLD). Fibrotic markers included Sirt6 (TGF-β/Smad2 inhibition), TIMP-1, CHI3L1, CXCL6, platelet GPIbα, and GGT, indicating the severity of the disease and their diagnostic or therapeutic potential. Overall, the risk of bias was low to moderate, and GRADE rated certainty of evidence was moderate. Conclusion: Emerging molecular biomarkers offered non-invasive diagnostic, prognostic, and therapeutic potential by reflecting important inflammatory and fibrotic pathways in CLD.