TY - JOUR
T1 - Novel prognostic biomarkers in decompensated cirrhosis
T2 - A systematic review and meta-analysis
AU - Juanola, Adrià
AU - Ma, Ann Thu
AU - de Wit, Koos
AU - Gananandan, Kohilan
AU - Roux, Olivier
AU - Zaccherini, Giacomo
AU - Jiménez, C. sar
AU - Tonon, Marta
AU - Solé, Cristina
AU - Villaseca, Clara
AU - Uschner, Frank E.
AU - Graupera, Isabel
AU - Pose, Elisa
AU - Moreta, Maria José
AU - Campion, Daniela
AU - Beuers, Ulrich
AU - Mookerjee, Rajeshawar P.
AU - Francoz, Claire
AU - Durand, Francois
AU - Vargas, Victor
AU - Piano, Salvatore
AU - Alonso, Sonia
AU - Trebicka, Jonel
AU - Laleman, Wim
AU - Asrani, Sumeet K.
AU - Soriano, German
AU - Alessandria, Carlo
AU - Serra-Burriel, Miquel
AU - Morales-Ruiz, Manuel
AU - Torres, Ferran
AU - Allegretti, Andrew S.
AU - Krag, Aleksander
AU - Caraceni, Paolo
AU - Watson, Hugh
AU - Abraldes, Juan G.
AU - Solà, Elsa
AU - Kamath, Patrick S.
AU - Hernaez, Ruben
AU - Ginès, Pere
N1 - Funding Information: This work has been supported by the European Commission Horizon 2020 (LIVERHOPE project number 731875), ISCIII-Subdireccin General de Evaluacin and European Regional Development Fund for the Plan Nacional I+D+I (grant number PI20/00579 to PG and PI18/00727 to ES), and the Agency for Administration of University and Research (grant number 2017SGR-01281 to PG, ES, EP). ATM received funding from the Canadian Association for the Study of Liver and the Canadian Liver Foundation. JT was supported by the German Research Foundation (DFG) project ID 403224013-SFB 1382 (A09), by the German Federal Ministry of Education and Research (BMBF) for the DEEP-HCC project and by the Hessian Ministry of Higher Education, Research and the Arts (HMWK) for the ENABLE and ACLF-I cluster projects. The MICROB-PREDICT (project ID 825694), DECISION (project ID 847949), GALAXY (project ID 668031) and IHMCSA (project ID A) projects have received funding from the European Unions Horizon 2020 research and innovation programme. Funding Information: FD consults for Biotest. VV consults for Promethera and is on the speakers bureau for Intercept. SP advises Mallinckrodt. HW is employed by Evotec and owns stock in Sanofi. PG consults for and received grants from Gilead, Grifols and Mallinckrodt, and consults for Novartis, Martin and Ferring. JT has received speaking and/or consulting fees from Versantis, Gore, Boehringer-Ingelheim, Falk, Grifols, Genfit and CSL Behring. RH is part of the Editorial Board of the Gut journal. Funding Information: This work has been supported by the European Commission Horizon 2020 (LIVERHOPE project number 731875), ISCIII‐Subdirección General de Evaluación and European Regional Development Fund for the Plan Nacional I+D+I (grant number PI20/00579 to PG and PI18/00727 to ES), and the Agency for Administration of University and Research (grant number 2017SGR‐01281 to PG, ES, EP). ATM received funding from the Canadian Association for the Study of Liver and the Canadian Liver Foundation. JT was supported by the German Research Foundation (DFG) project ID 403224013—SFB 1382 (A09), by the German Federal Ministry of Education and Research (BMBF) for the DEEP-HCC project and by the Hessian Ministry of Higher Education, Research and the Arts (HMWK) for the ENABLE and ACLF-I cluster projects. The MICROB-PREDICT (project ID 825694), DECISION (project ID 847949), GALAXY (project ID 668031) and IHMCSA (project ID A) projects have received funding from the European Union’s Horizon 2020 research and innovation programme. Publisher Copyright: © 2023 BMJ Publishing Group. All rights reserved.
PY - 2023/10/26
Y1 - 2023/10/26
N2 - Background: Patients with decompensated cirrhosis experience high mortality rates. Current prognostic scores, including the model for end-stage liver disease (MELD), may underperform in settings other than in those they were initially developed. Novel biomarkers have been proposed to improve prognostication accuracy and even to predict development of complications. Methods: We performed a systematic review and meta-analysis on novel urine and blood biomarkers and their ability to predict 90-day mortality in patients with decompensated cirrhosis. Secondary outcomes included 28-day and 1-year mortality, and development of acute-on-chronic liver failure, acute kidney injury and other complications. To overcome differences in units, temporal changes in assays and reporting heterogeneity, we used the ratio of means (RoM) as measure of association for assessing strength in predicting outcomes. An RoM>1 implies that the mean biomarker level is higher in those that develop the outcome than in those that do not. Results: Of 6629 unique references, 103 were included, reporting on 29 different biomarkers, with a total of 31 362 biomarker patients. Most studies were prospective cohorts of hospitalised patients (median Child-Pugh-Turcotte score of 9 and MELD score of 18). The pooled 90-day mortality rate was 0.27 (95% CI 0.24 to 0.29). The RoM for predicting 90-day mortality was highest for interleukin 6 (IL-6) (2.56, 95% CI 2.39 to 2.74), followed by urinary neutrophil gelatinase-associated lipocalin (uNGAL) (2.42, 95% CI 2.20 to 2.66) and copeptin (2.33, 95% CI 2.17 to 2.50). These RoMs were all higher than for MELD (1.44, 95% CI 1.42 to 1.46). Conclusion: Novel biomarkers, including IL-6, uNGAL and copeptin, can probably improve prognostication of patients with decompensated cirrhosis compared with MELD alone.
AB - Background: Patients with decompensated cirrhosis experience high mortality rates. Current prognostic scores, including the model for end-stage liver disease (MELD), may underperform in settings other than in those they were initially developed. Novel biomarkers have been proposed to improve prognostication accuracy and even to predict development of complications. Methods: We performed a systematic review and meta-analysis on novel urine and blood biomarkers and their ability to predict 90-day mortality in patients with decompensated cirrhosis. Secondary outcomes included 28-day and 1-year mortality, and development of acute-on-chronic liver failure, acute kidney injury and other complications. To overcome differences in units, temporal changes in assays and reporting heterogeneity, we used the ratio of means (RoM) as measure of association for assessing strength in predicting outcomes. An RoM>1 implies that the mean biomarker level is higher in those that develop the outcome than in those that do not. Results: Of 6629 unique references, 103 were included, reporting on 29 different biomarkers, with a total of 31 362 biomarker patients. Most studies were prospective cohorts of hospitalised patients (median Child-Pugh-Turcotte score of 9 and MELD score of 18). The pooled 90-day mortality rate was 0.27 (95% CI 0.24 to 0.29). The RoM for predicting 90-day mortality was highest for interleukin 6 (IL-6) (2.56, 95% CI 2.39 to 2.74), followed by urinary neutrophil gelatinase-associated lipocalin (uNGAL) (2.42, 95% CI 2.20 to 2.66) and copeptin (2.33, 95% CI 2.17 to 2.50). These RoMs were all higher than for MELD (1.44, 95% CI 1.42 to 1.46). Conclusion: Novel biomarkers, including IL-6, uNGAL and copeptin, can probably improve prognostication of patients with decompensated cirrhosis compared with MELD alone.
KW - liver cirrhosis
UR - http://www.scopus.com/inward/record.url?scp=85175973662&partnerID=8YFLogxK
U2 - https://doi.org/10.1136/gutjnl-2023-329923
DO - https://doi.org/10.1136/gutjnl-2023-329923
M3 - Article
C2 - 37884354
SN - 0017-5749
VL - 73
SP - 156
EP - 165
JO - Gut
JF - Gut
IS - 1
M1 - gutjnl-2023-329923
ER -