Meta-analysis of individual patient data of albumin dialysis in acute-on-chronic liver failure: focus on treatment intensity

Background: Acute-on-chronic liver failure (ACLF) is a common complication of cirrhosis characterized by single or multiple organ failures and high short-term mortality. Treatment of ACLF consists of standard medical care (SMC) and organ(s) support. Whether the efficacy of artificial liver support (ALS) depends on the severity of ACLF or on the intensity of this treatment, or both, is unclear. This study aimed to further assess these issues. Methods: We performed an individual patient data meta-analysis assessing the efficacy of Molecular Adsorbent Recirculating System (MARS) in ACLF patients enrolled in prior randomized control trials (RCTs). The meta-analysis was designed to assess the effect of patient severity (ACLF grade) and treatment intensity [low-intensity therapy (LIT), SMC alone or SMC plus <= 4 MARS sessions, high-intensity therapy (HIT), SMC plus > 4 MARS sessions] on mortality. Results: Three RCTs suitable for the meta-analysis (n = 285, ACLF patients = 165) were identified in a systematic review. SMC plus MARS (irrespective of the number of sessions) did not improve survival compared with SMC alone, neither in the complete population nor in the ACLF patients. Survival, however, was significantly improved in the subgroup of patients receiving HIT both in the entire cohort (10-day survival: 98.6% versus 82.8%, p = 0.001; 30-day survival: 73.9% versus 64.3%, p = 0.032) and within the ACLF patients (10-day survival: 97.8% versus 78.6%, p = 0.001; 30-day survival: 73.3% versus 58.5%, p = 0.041). Remarkably, HIT increased survival independently of ACLF grade. Independent predictors of survival were age, Model for End-Stage Liver Disease (MELD), ACLF grade, number of MARS sessions received, and intensity of MARS therapy. Conclusion: HIT with albumin dialysis may improve survival in patients with ACLF. Appropriate treatment schedules should be determined in future clinical trials.