The Optimal Therapeutic Window for Nonbioartificial Liver Support in Acute-On-Chronic Liver Failure: A Meta-Analysis...

NBALS efficacy in ACLF remains controversial. We aimed to determine if a "therapeutic window" exists by stratifying clinical outcomes based on baseline Model for End-Stage Liver Disease (MELD) scores. We searched PubMed, Embase, Cochrane Library, and Web of Science for RCTs and PSM-cohorts comparing NBALS to standard medical therapy (SMT). Primary outcome was 28-day mortality; MELD-stratified subgroup analyses and random-effects meta-regression were performed. Eleven studies (comprising 12 datasets) involving 1958 patients (991 NBALS vs. 967 SMT) were included. Overall, NBALS significantly reduced 28-day mortality compared with SMT (pooled RR 0.72, 95% CI [0.63-0.83], I² = 2.8%). Subgroup analysis suggested a clinical trend toward a distinct therapeutic window: the survival benefit was most significant in the Intermediate MELD group (25-30) (RR 0.65, 95% CI [0.52-0.81], I² = 0%) and the High MELD group (> 30) (RR 0.75, 95% CI [0.58-0.98], I² = 0%), while substantial uncertainty exists regarding the survival benefit in the Low MELD group (< 25) (RR 0.49, 95% CI [0.08-2.81], I² = 67.9%). Meta-regression confirmed that the maximum survival benefit of NBALS is concentrated within a baseline MELD range of approximately 25 to 32. Furthermore, NBALS group achieved a significantly higher reduction in total bilirubin compared to SMT (pooled MD 98.15, 95% CI [66.50-129.79], I² = 99.2%). NBALS significantly improves short-term survival in ACLF, suggesting a potential therapeutic window around a baseline MELD range of 25-32. Early stratification based on disease severity is crucial for optimizing NBALS application. Trial Registration: PROSPERO CRD420261334987.