Novel prognostic biomarkers in decompensated cirrhosis: A systematic review and meta-analysis

Adrià Juanola, Ann Thu Ma, Koos De Wit, Kohilan Gananandan, Olivier Roux, Giacomo Zaccherini, César Jiménez, Marta Tonon, Cristina Solé, Clara Villaseca, Frank E. Uschner, Isabel Graupera, Elisa Pose, Maria José Moreta, Daniela Campion, Ulrich Beuers, Rajeshawar P. Mookerjee, Claire Francoz, Francois Durand, Victor VargasSalvatore Piano, Sonia Alonso, Jonel Trebicka, Wim Laleman, Sumeet K. Asrani, German Soriano, Carlo Alessandria, Miquel Serra-Burriel, Manuel Morales-Ruiz, Ferran Torres, Andrew S. Allegretti, Aleksander Krag, Paolo Caraceni, Hugh Watson, Juan G. Abraldes, Elsa Solà, Patrick S. Kamath, Ruben Hernaez, Pere Ginès*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review


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.

Original languageEnglish
Article numbergutjnl-2023-329923
Pages (from-to)156-165
Number of pages10
Issue number1
Publication statusPublished - 26 Oct 2023


  • Liver cirrhosis


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