TY - JOUR
T1 - Metabolomics as a tool to predict the risk of decompensation or liver related death in patients with compensated cirrhosis
AU - Nicoară-Farcău, Oana
AU - Lozano, Juan Jose
AU - Alonso, Cristina
AU - Sidorova, Julia
AU - Villanueva, Càndid
AU - Albillos, Augustín
AU - Genescà, Joan
AU - Llop, Elba
AU - Calleja, Jose Luis
AU - Aracil, Carles
AU - Bañares, Rafael
AU - Morillas, Rosa
AU - Poca, Maria
AU - Peñas, Beatriz
AU - Augustin, Salvador
AU - Tantău, Marcel
AU - Thompson, Marcos
AU - Perez-Campuzano, Valeria
AU - Baiges, Anna
AU - Turon, Fanny
AU - Hernandez-Gea, Virginia
AU - Abraldes, Juan G
AU - Tapias, Edilmar Alvarado
AU - Torres, Ferran
AU - Bosch, Jaime
AU - Garcia-Pagan, Juan Carlos
N1 - Publisher Copyright:
Copyright © 2023 American Association for the Study of Liver Diseases.
PY - 2023/6/1
Y1 - 2023/6/1
N2 - 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.
AB - 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.
KW - Adrenergic beta-Antagonists/therapeutic use
KW - Humans
KW - Hypertension, Portal/complications
KW - Liver Cirrhosis
KW - Portal Pressure
KW - Proportional Hazards Models
UR - https://www.mendeley.com/catalogue/4c70050b-b9e8-3b47-82a4-ed2db7bef8cf/
UR - http://www.scopus.com/inward/record.url?scp=85159410784&partnerID=8YFLogxK
U2 - 10.1097/hep.0000000000000316
DO - 10.1097/hep.0000000000000316
M3 - Article
C2 - 36811400
SN - 0270-9139
VL - 77
SP - 2052
EP - 2062
JO - Hepatology
JF - Hepatology
IS - 6
ER -