Metabolomics as a tool to predict the risk of decompensation or liver-related death in patients with compensated cirrhosis : Hepatology

Secondary Logo

Journal Logo

Advanced Search
Original Articles: Liver Failure/Cirrhosis/Portal Hypertension

Metabolomics as a tool to predict the risk of decompensation or liver-related death in patients with compensated cirrhosis

Nicoară-Farcău, Oana1,2; Lozano, Juan J.3,4; Alonso, Cristina5; Sidorova, Julia3,4; Villanueva, Càndid4,6,7; Albillos, Augustín4,8; Genescà, Joan4,7,9; Llop, Elba4,10; Calleja, Jose L.4,10; Aracil, Carles11; Bañares, Rafael4,12; Morillas, Rosa4,7,13; Poca, Maria4,6; Peñas, Beatriz4,8; Augustin, Salvador4,7,9; Tantău, Marcel2; Thompson, Marcos1,14; Perez-Campuzano, Valeria1; Baiges, Anna1,4; Turon, Fanny1,4; Hernández-Gea, Virginia1,4; Abraldes, Juan G.1,4,15; Tapias, Edilmar A.4,6; Torres, Ferran16,17; Bosch, Jaime1,4,18; García-Pagán, Juan C.1,4;  on behalf of the PreDesCI Study Investigators

Author Information

1Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain

2Gastroenterology Department, Regional Institute of Gastroenterology and Hepatology ‘Prof. Dr. Octavian Fodor’, University of Medicine and Pharmacy ‘Iuliu Hatieganu’, Cluj-Napoca, Romania

3Bioinformatics Platform, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

4Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto De Salud Carlos III, Spain

5OWL Metabolomics, Bizkaia, Spain

6Hospital De La Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain

7Autonomus University of Barcelona, Barcelona, Spain

8Ramón y Cajal University Hospital, Ramón y Cajal Institute of Health Research (IRYCIS), University of Alcalá, Madrid, Spain

9Liver Unit, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institute of Research (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain

10Puerta de Hierro University Hospital, Puerta de Hierro Hospital, Research Institute, Autonomous University of Madrid, Madrid, Spain

11Institute of Biomedical Research, Arnau de Vilanova University Hospital (IRBLleida), Lleida, Spain

12Gregorio Marañón University General Hospital, Gregorio Marañón Sanitary Research Institute, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain

13Hepatology Department, Hospital Germans Trias I Pujol, Germans Trias I Pujol Research Institute, Badalona, Spain

14Hepatology Department, Hospital Universitario Austral, Buenos Aires, Argentina

15Liver Unit, University of Alberta, Edmonton, Alberta, Canada

16Medical Statistics Core Facility, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

17Biostatistics Unit, Medical School, Universitat Autònoma de Barcelona, Barcelona, Spain

18Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, Switzerland

Abbreviations: ALD, alcohol-associated liver disease;, AUROC, area under the receiver operating characteristic; CSPH, clinically significant portal hypertension; LSM, liver stiffness measurement; MS, mass spectrometry; NSBB, nonselective beta-blockers

Correspondence Juan C. Garcia-Pagan, Barcelona Hepatic Hemodynamic Laboratory Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, Villarroel 170 Barcelona 08036, Spain. Email: [email protected]

Supplemental Digital Content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal's website, www.hepjournal.com.

Hepatology 77(6):p 2052-2062, June 2023. | DOI: 10.1097/HEP.0000000000000316
  • Buy
  • SDC
  • Infographic

Abstract

Background and Aims: 

Patients with compensated cirrhosis with clinically significant portal hypertension (CSPH: HVPG >10 mm Hg) have a high risk of decompensation. HVPG is, however, an invasive procedure not available in all centers. The present study aims to assess whether metabolomics can improve the capacity of clinical models in predicting clinical outcomes in these compensated patients.

Approach and Results: 

This is a nested study from the PREDESCI cohort (an RCT of nonselective beta-blockers vs. placebo in 201 patients with compensated cirrhosis and CSPH), including 167 patients for whom a blood sample was collected. A targeted metabolomic serum analysis, using ultra-high-performance liquid chromatography-mass spectrometry, was performed. Metabolites underwent univariate time-to-event cox regression analysis. Top-ranked metabolites were selected using Log-Rank p-value to generate a stepwise cox model. Comparison between models was done using DeLong test. Eighty-two patients with CSPH were randomized to nonselective beta-blockers and 85 to placebo. Thirty-three patients developed the main endpoint (decompensation/liver-related death). The model, including HVPG, Child-Pugh, and treatment received (HVPG/Clinical model), had a C-index of 0.748 (CI95% 0.664–0.827). The addition of 2 metabolites, ceramide (d18:1/22:0) and methionine (HVPG/Clinical/Metabolite model), significantly improved the model’s performance [C-index of 0.808 (CI95% 0.735–0.882); p=0.032]. The combination of these 2 metabolites together with Child-Pugh and the type of treatment received (Clinical/Metabolite model) had a C-index of 0.785 (CI95% 0.710–0.860), not significantly different from the HVPG-based models including or not metabolites.

Conclusions: 

In patients with compensated cirrhosis and CSPH, metabolomics improves the capacity of clinical models and achieves similar predictive capacity than models including HVPG.

Abstract
Export

Copyright © 2023 American Association for the Study of Liver Diseases.

Full Text Access for Subscribers:

AASLD members log in here
AASLD members log in here
AASLD members log in here

Not a Subscriber?

Buy
Request Permissions
Become a Society Member

You can read the full text of this article if you:

Access through Ovid