Serum miR-181b-5p predicts ascites onset in patients with compensated cirrhosis

Ana Garcia Garcia de Paredes; Càndid Villanueva; Carolina Blanco; Joan Genescà; Nicolo Manicardi; Juan Carlos Garcia-Pagan; Jose Luis Calleja; Carlos Aracil; Rosa M Morillas; Maria Poca; Beatriz Peñas; Salvador Augustin; Juan G Abraldes; Eldimar Alvarado; Félix Royo; Maria Laura Garcia-Bermejo; Juan Manuel Falcon-Perez; Rafael Bañares; Jaime Bosch; Jordi Gracia-Sancho; Agustin Albillos

doi:10.1016/j.jhepr.2021.100368

Serum miR-181b-5p predicts ascites onset in patients with compensated cirrhosis

JHEP Rep. 2021 Sep 27;3(6):100368. doi: 10.1016/j.jhepr.2021.100368. eCollection 2021 Dec.

Authors

Ana Garcia Garcia de Paredes¹, Càndid Villanueva^{2

3}, Carolina Blanco⁴, Joan Genescà^{3

5}, Nicolo Manicardi⁶, Juan Carlos Garcia-Pagan^{3

7}, Jose Luis Calleja⁸, Carlos Aracil⁹, Rosa M Morillas^{3

10

11}, Maria Poca², Beatriz Peñas¹, Salvador Augustin⁵, Juan G Abraldes^{7

12}, Eldimar Alvarado², Félix Royo^{3

13}, Maria Laura Garcia-Bermejo⁴, Juan Manuel Falcon-Perez^{3

13}, Rafael Bañares^{3

14}, Jaime Bosch^{3

7

15}, Jordi Gracia-Sancho^{3

6}, Agustin Albillos^{1

3}

Affiliations

¹ Gastroenterology and Hepatology Department, Hospital Universitario Ramon y Cajal, Instituto Ramon y Cajal de Investigacion Sanitaria (IRYCIS), Universidad de Alcala, Madrid, Spain.
² Hospital of Santa Creu and Sant Pau, Autonomous University of Barcelona, Hospital Sant Pau Biomedical Research Institute (IIB Sant Pau) Barcelona, Spain.
³ Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain.
⁴ Biomarkers and Therapeutic Targets Group, Instituto Ramon y Cajal de Investigacion Sanitaria (IRYCIS), Madrid, Spain.
⁵ Liver Unit, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Research (VHIR), Vall d'Hebron Barcelona Hospital campus, Autonomous University of Barcelona, Barcelona, Spain.
⁶ Liver Vascular Biology Research Group, IDIBAPS Biomedical Research Institute, Barcelona, Spain.
⁷ Barcelona Hepatic Haemodynamic Laboratory, Liver Unit, Institute of Digestive and Metabolic Diseases, August Pi i Sunyer Institute of Biomedical Research, Hospital Clínic, Barcelona, Spain.
⁸ Gastroenterology and Hepatology Department, Hospital Universitario Puerta de Hierro, Puerta de Hierro Hospital Research Institute, Autonomous University of Madrid, Madrid, Spain.
⁹ Institute of Biomedical Research, Arnau de Vilanova University Hospital (IRB Lleida), Lleida, Spain.
¹⁰ Liver Section, Hospital Universitari Germans Trias i Pujol, IGTP, Badalona, Spain.
¹¹ Universitat Autònoma de Barcelona, Spain.
¹² Liver Unit, Division of Gastroenterology, University of Alberta, Edmonton, Canada.
¹³ Exosomes Laboratory, Center for Cooperative Research in Biosciencies (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, 48160, Spain.
¹⁴ Gastroenterology and Hepatology Department, Hospital Universitario Gregorio Marañon, Instituto de Investigacion Sanitaria Gregorio Marañon (IiSGM), Universidad Complutense de Madrid, Madrid, Spain.
¹⁵ Department of Biomedical Research and University Clinic for Visceral Medicine and Surgery, Inselspital, Bern, Switzerland.

Abstract

Background & aims: Treatment with non-selective beta-blockers (NSBBs) reduces the risk of ascites, which is the most common decompensating event in cirrhosis. This study aimed to assess the ability of a serum microRNA (miRNA) signature to predict ascites formation and the hemodynamic response to NSBBs in compensated cirrhosis.

Methods: Serum levels of miR-452-5p, miR-429, miR-885-5p, miR-181b-5p, and miR-122-5p were analyzed in patients with compensated cirrhosis (N = 105). Hepatic venous pressure gradient (HVPG) was measured at baseline, after intravenous propranolol, and 1 year after randomization to NSBBs (n = 52) or placebo (n = 53) (PREDESCI trial). miRNAs were analyzed at baseline and at 1 year.

Results: Nineteen patients (18%) developed ascites, of whom 17 developed ascites after 1 year. miR-181b-5p levels at 1 year, but not at baseline, were higher in patients that developed ascites. The AUC of miR-181b-5p at 1 year to predict ascites was 0.7 (95% CI 0.59-0.78). miR-429 levels were lower at baseline in acute HVPG responders to NSBBs (AUC 0.65; 95% CI, 0.53-0.76), but levels at baseline and at 1 year were not associated with the HVPG response to NSBBs at 1 year.

Conclusions: Serum miR-181b-5p is a promising non-invasive biomarker to identify patients with compensated cirrhosis at risk of ascites development.

Lay summary: Ascites marks the transition from the compensated to decompensated stage in cirrhosis and indicates a worsening in prognosis. There are currently no easily accessible tools to identify patients with compensated cirrhosis at risk of developing ascites. We evaluated the levels of novel molecules termed microRNAs in the blood of patients with compensated cirrhosis and observed that miR-181b-5p can predict which patients are going to develop ascites.

Keywords: Ascites; CSPH, clinically significant portal hypertension; Ct, cycle threshold; HVPG, hepatic venous pressure gradient; NSBBs, non-selective beta-blockers; ROC, receiver-operating characteristic; beta-blockers; cirrhosis; miRNAs, microRNAs; microRNA; portal hypertension.