P39 Systemic inflammation associated microRNA as novel biomarkers for clinical decompensation in patients with cirrhosis

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Backgrounds and Aims As the global prevalence of chronic liver disease continues to rise, the need to determine which patients will develop end-stage liver disease and require liver transplantation is increasingly important. However, current prognostic models are impacted by multiple factors including underlying cirrhosis aetiology and mode of decompensation. We have previously shown that microRNA can be used to prognosticate patients with acute liver failure (ALF). We aimed to determine microRNA profiles associated with clinical decompensation and 90-day transplant free survival (TxFS). Methods We performed a retrospective cohort study using plasma samples from patients admitted to a UK transplant centre between 2014–2021 across the spectrum of cirrhosis (n=154), ALF, sepsis (n=20) and healthy controls (HC) (n=20). A qPCR panel of 21 microRNA was utilised to assess microRNA expression across clinical groups and to predict clinical decompensation and 90-day TxFS in patients with cirrhosis. Univariate and multivariate analyses were performed. Results microRNA expression profiles in patients with acute-on-chronic liver failure were more similar to patients with sepsis than ALF (figure 1). miR-122, -223, -24, -27a, -29b, -30a, -330 and -663 were differentially expressed in patients with decompensated liver disease compared to HC and patients with compensated cirrhosis. These microRNA significantly correlated with common laboratory markers of systemic inflammation and were shown to be involved in processes governing the epigenetic response to systemic inflammation on MetaCore™ pathway analysis (Z score=188.35). A model including miR-24 and miR-27a was able to differentiate decompensated cirrhosis states from compensated cirrhosis states and HC (AUC 0.77 (95% CI 0.69–0.85)). Excluding different decompensated subgroups (ACLF, acute decompensation and chronic decompensated cirrhosis) did not impact model performance. However, excluding HC individuals worsened model performance (AUC 0.69 (95% CI 0.56–0.81)). 6/20 patients in the compensated cirrhosis group subsequently decompensated the following year. Excluding these patients from the previous sensitivity analysis improved model performance (AUC 0.74 (95% CI 0.60–0.88)) and excluding these patients from the overall model improved model performance (AUC 0.81 (95% CI 0.71–0.89)). Individual microRNA had limited prognostic value in predicting patients who achieved a 90-day TxFS with expression impacted by disease severity, decompensation manifestation and underlying cirrhosis aetiology. Conclusion Our findings demonstrate that microRNA associated with systemic inflammation are associated with clinical decompensation. These microRNA may be expressed prior to a decompensation event and therefore represent potential novel prognostic biomarkers in cirrhosis.

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