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.
- liver cirrhosis
Data availability statement
All data relevant to the study are included in the article or uploaded as online supplemental information. The data that support the findings of this study are available from the corresponding author, (PG), on reasonable request.
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AJ and ATM are joint first authors.
Collaborators M Aban, R Andrade, P Angeli, S K Asrani, E Avitabile, O Bassegoda, M Bernardi, M Carol, M Cervera, MT Chiappa, V Esnault, N Fabrellas, J Farrés, P Ferstl, J Gratacós-Ginès, P Ginès, M Joyera, M Korenjak, S Martínez, S Montagnese, L Napoleone, G Nicolao, E Palacio, M Pavesi, M Pérez- Guasch, A B Rubio, M Schulz, M Simon-Talero, A Vives.
Contributors All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. AJ designed the study, acquired data, developed the database, undertook statistical analyses and interpretation, and drafted and revised the manuscript. ATM designed the study, acquired data, developed the database, interpreted the data, and drafted and revised the manuscript. KdW, KG and OR acquired and interpreted data, contributed to manuscript drafting and revision. GZ, CJ, MT, CS, CV, FEU, IG, EP and MJM acquired data and revised the manuscript. ES designed the study, acquired and interpreted data, and revised the manuscript. RH designed the study, acquired data, developed the database, interpreted the data, and drafted and revised the manuscript. DC, UB, RM, CF, FD, VV, SP, SAsrani, JT, WL, SAsrani, GS, CA, MS-B, MM, FT, AA, AK, PC, HW, JGA, PSK and PG revised the manuscript. RH and PG Shared co-principal investigator. AJ, ATM, RH and PG accept full responsibility for the work and/or the conduct of the study, had access to the data and controlled the decision to publish.
Funding 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.
Disclaimer The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the U.S. Department of Veterans Affairs or the United States government.
Competing interests 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.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
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