Klementina Ocskay1, Anna Kanjo1,2, Noémi Gede1,3, Zsolt Szakács1, Gabriella Pár4, Bálint Erőss1, Jan Stange5, Steffen Mitzner5, Péter Hegyi1,6,7, Zsolt Molnár8,9. 1. Institute for Translational Medicine, Medical School, University of Pécs, Szigeti út 12. 2nd floor, Pécs, 7624, Hungary. 2. Heim Pál National Paediatric Institute, Budapest, Hungary. 3. Institute of Bioanalysis, Medical School, University of Pécs, Pécs, Hungary. 4. Division of Gastroenterology, First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary. 5. Division of Nephrology, Department of Medicine, University of Rostock, Rostock, Germany. 6. First Department of Medicine, University of Szeged, Szeged, Hungary. 7. Translational Medicine Foundation, Szeged, Hungary. 8. Institute for Translational Medicine, Medical School, University of Pécs, Szigeti út 12. 2nd floor, Pécs, 7624, Hungary. zsoltmolna@gmail.com. 9. Department of Anaesthesiology and Intensive Therapy, Faculty of Medicine, Poznan University of Medical Sciences, Poznan, Poland. zsoltmolna@gmail.com.
Abstract
BACKGROUND: The role of artificial and bioartificial liver support systems in acute-on-chronic liver failure (ACLF) is still controversial. We aimed to perform the first network meta-analysis comparing and ranking different liver support systems and standard medical therapy (SMT) in patients with ACLF. METHODS: The study protocol was registered with PROSPERO (CRD42020155850). A systematic search was conducted in five databases. We conducted a Bayesian network meta-analysis of randomized controlled trials assessing the effect of artificial or bioartificial liver support systems on survival in patients with ACLF. Ranking was performed by calculating the surface under cumulative ranking (SUCRA) curve values. The RoB2 tool and a modified GRADE approach were used for the assessment of the risk of bias and quality of evidence (QE). RESULTS: In the quantitative synthesis 16 trials were included, using MARS®, Prometheus®, ELAD®, plasma exchange (PE) and BioLogic-DT®. Overall (OS) and transplant-free (TFS) survival were assessed at 1 and 3 months. PE significantly improved 3-month OS compared to SMT (RR 0.74, CrI: 0.6-0.94) and ranked first on the cumulative ranking curves for both OS outcomes (SUCRA: 86% at 3 months; 77% at 1 month) and 3-month TFS (SUCRA: 87%) and second after ELAD for 1-month TFS (SUCRA: 76%). Other comparisons did not reach statistical significance. QE was moderate for PE concerning 1-month OS and both TFS outcomes. Other results were of very low certainty. CONCLUSION: PE seems to be the best currently available liver support therapy in ACLF regarding 3-month OS. Based on the low QE, randomized trials are needed to confirm our findings for already existing options and to introduce new devices.
BACKGROUND: The role of artificial and bioartificial liver support systems in acute-on-chronic liver failure (ACLF) is still controversial. We aimed to perform the first network meta-analysis comparing and ranking different liver support systems and standard medical therapy (SMT) in patients with ACLF. METHODS: The study protocol was registered with PROSPERO (CRD42020155850). A systematic search was conducted in five databases. We conducted a Bayesian network meta-analysis of randomized controlled trials assessing the effect of artificial or bioartificial liver support systems on survival in patients with ACLF. Ranking was performed by calculating the surface under cumulative ranking (SUCRA) curve values. The RoB2 tool and a modified GRADE approach were used for the assessment of the risk of bias and quality of evidence (QE). RESULTS: In the quantitative synthesis 16 trials were included, using MARS®, Prometheus®, ELAD®, plasma exchange (PE) and BioLogic-DT®. Overall (OS) and transplant-free (TFS) survival were assessed at 1 and 3 months. PE significantly improved 3-month OS compared to SMT (RR 0.74, CrI: 0.6-0.94) and ranked first on the cumulative ranking curves for both OS outcomes (SUCRA: 86% at 3 months; 77% at 1 month) and 3-month TFS (SUCRA: 87%) and second after ELAD for 1-month TFS (SUCRA: 76%). Other comparisons did not reach statistical significance. QE was moderate for PE concerning 1-month OS and both TFS outcomes. Other results were of very low certainty. CONCLUSION: PE seems to be the best currently available liver support therapy in ACLF regarding 3-month OS. Based on the low QE, randomized trials are needed to confirm our findings for already existing options and to introduce new devices.
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