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  • Diagnostic Value of Circulating Long Non-coding RNAs in Liver Fibrosis, Cirrhosis, and Hepatocellular Carcinoma

  • Zahra Damirchi,1,*
    1. Tehran Azad University of Medical Sciences


  • Introduction: The liver plays a central role in metabolic homeostasis and in regulating the immune system, and Failure of its function can lead to serious and life-threatening. So, early detection of chronic liver diseases is essential to prevent the progression of liver damage to fibrosis, cirrhosis, and HCC. Since the existing and common diagnostic methods are invasive, the importance of having alternative methods that allow for non-invasive, accurate, and repeatable assessment of molecular changes involved in regulating inflammation, fibrogenesis, and extracellular matrix remodeling in carcinogenesis becomes more evident. The identification of certain Long non-coding RNAs (lncRNAs) in serum, plasma, and extracellular vesicles has made it possible to assess these molecular changes through blood sampling. Despite extensive studies on biomarkers like HULC, MALAT1, and H19, they have yielded inconsistent findings regarding clinical value and reliability. The aim of this study is to summarize the existing evidence on the potential of circulating lncRNAs as biomarkers for differential diagnosis and monitoring of chronic liver diseases and HCC.
  • Methods: In this review, articles published from 2010 to 2026 in the PubMed and Google Scholar databases were examined using the keywords lncRNA, NAFLD, hepatitis, fibrosis, cirrhosis, and HCC, and eventually 15 articles that directly focused on circulating lncRNAs in chronic hepatitis, metabolic liver diseases, fibrosis, cirrhosis, or HCC were selected. In these studies, patients were categorized based on disease stage, and sample sources including tissue, serum, extracellular vesicles, and plasma were analyzed for diagnostic and prognostic purposes. Evidence regarding diagnostic accuracy, expression changes and levels, as well as findings related to disease progression and treatment response, were interpreted comparatively.
  • Results: Since lncRNAs have been reported to be used in HCC detection with high sensitivity and specificity, they have become a reliable complement to conventional diagnostic methods. However, upon closer examination, it was observed that some of them, such as HULC, have relatively stable expression patterns and clinical associations, whereas others, such as MALAT1 and H19, have shown opposite biological roles, acting as tumor suppressors versus oncogenes and showing increased or decreased expression in fibrosis. Despite growing evidence, heterogeneity in patient populations, sample sources, and measurement methods has kept the use of these biomarkers for prognosis and treatment monitoring still at an early stage.
  • Conclusion: Circulating lncRNAs, if laboratory processes are standardized, methods are reported more transparently, and validation is performed in independent and multicenter populations, could be introduced as potential candidates for blood-based biomarkers in liver diseases.
  • Keywords: Circulating lncRNAs, Hepatocellular Carcinoma, Liver Fibrosis, Non-invasive Biomarkers, Cirrhosis.

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