microRNA associated with hepatocyte injury and systemic inflammation may predict adverse outcomes in cirrhotic patients

TY - JOUR

T1 - microRNA associated with hepatocyte injury and systemic inflammation may predict adverse outcomes in cirrhotic patients

AU - Tavabie, Oliver D

AU - Patel, Vishal C

AU - Salehi, Siamak

AU - Stamouli, Marilena

AU - Trovato, Francesca M

AU - Maxan, Maria-Emanuela

AU - Jeyanesan, Dhaarica

AU - Rivera, Savannah

AU - Mujib, Salma

AU - Zamalloa, Ane

AU - Corcoran, Eleanor

AU - Menon, Krishna

AU - Prachalias, Andreas

AU - Heneghan, Michael A

AU - Agarwal, Kosh

AU - McPhail, Mark J W

AU - Aluvihare, Varuna R

N1 - Publisher Copyright: © The Author(s) 2024.

PY - 2024/10/11

Y1 - 2024/10/11

N2 - 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 perform sub-optimally. We aim to determine microRNA profiles associated with clinical decompensation and mortality/transplantation within 1 year. We examined microRNA expression profiles in plasma samples from patients across the spectrum of cirrhosis (n = 154), acute liver failure (ALF) (n = 22), sepsis (n = 20) and healthy controls (HC) (n = 20). We demonstrated that a microRNA-based model (miR-24 and -27a) associated with systemic inflammation differentiated decompensated cirrhosis states from compensated cirrhosis and HC (AUC 0.77 (95% CI 0.69-0.85)). 6 patients within the compensated cirrhosis group decompensated the subsequent year and their exclusion improved model performance (AUC 0.81 (95% CI 0.71-0.89)). miR-191 (associated with liver injury) predicted risk of mortality across the cohort when acutely decompensated and acute-on-chronic-liver failure patients were included. When they were excluded miR-24 (associated with systemic inflammation) predicted risk of mortality. Our findings demonstrate that microRNA associated with systemic inflammation and liver injury predict adverse outcomes in cirrhosis. miR-24 and -191 require further investigation as prognostic biomarkers and therapeutic targets for patients with liver disease.

AB - 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 perform sub-optimally. We aim to determine microRNA profiles associated with clinical decompensation and mortality/transplantation within 1 year. We examined microRNA expression profiles in plasma samples from patients across the spectrum of cirrhosis (n = 154), acute liver failure (ALF) (n = 22), sepsis (n = 20) and healthy controls (HC) (n = 20). We demonstrated that a microRNA-based model (miR-24 and -27a) associated with systemic inflammation differentiated decompensated cirrhosis states from compensated cirrhosis and HC (AUC 0.77 (95% CI 0.69-0.85)). 6 patients within the compensated cirrhosis group decompensated the subsequent year and their exclusion improved model performance (AUC 0.81 (95% CI 0.71-0.89)). miR-191 (associated with liver injury) predicted risk of mortality across the cohort when acutely decompensated and acute-on-chronic-liver failure patients were included. When they were excluded miR-24 (associated with systemic inflammation) predicted risk of mortality. Our findings demonstrate that microRNA associated with systemic inflammation and liver injury predict adverse outcomes in cirrhosis. miR-24 and -191 require further investigation as prognostic biomarkers and therapeutic targets for patients with liver disease.

KW - Humans

KW - Liver Cirrhosis/genetics

KW - MicroRNAs/genetics

KW - Male

KW - Female

KW - Middle Aged

KW - Inflammation/genetics

KW - Prognosis

KW - Hepatocytes/metabolism

KW - Biomarkers/blood

KW - Adult

KW - Aged

KW - Acute-On-Chronic Liver Failure/genetics

KW - Case-Control Studies

KW - Liver Transplantation/adverse effects

UR - http://www.scopus.com/inward/record.url?scp=85206123308&partnerID=8YFLogxK

U2 - 10.1038/s41598-024-72416-w

DO - 10.1038/s41598-024-72416-w

M3 - Article

C2 - 39394217

SN - 2045-2322

VL - 14

SP - 23831

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 23831

ER -