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

Abstract

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.

Uncertainty in the impact of liver support systems in acute-on-chronic liver failure: a systematic review and network meta-analysis

“…The recruitment period for the included trials ranges from March 1997 until February 2015, which could impose chronological bias. Variance in SMT and treatment dose also could have influenced outcomes [62]. Due to the differences in treatment dose, cut-offs and reporting protocols, data on HE, laboratory parameters, and AEs could not be analyzed quantitatively.…”

Leukocytes, Systemic Inflammation and Immunopathology in Acute-on-Chronic Liver Failure

“…Other therapies based on HSA but alternative to infusions are extracorporeal liver support systems based on albumin dialysis or plasma exchange. This is the case of recent studies showing that patients treated with extracorporeal liver support systems had improved survival [106][107][108].…”

Bleeding Complications Associated With the Molecular Adsorbent Recirculating System: A Retrospective Observational Study

“…According to a meta-analysis published in 2012 [5], MARS decreases total bilirubin and clinical symptoms of hepatic encephalopathy, but the incidence of bleeding complications was 24.1% compared with 10.2% among patients receiving standard medical support (P=0.007), and a consistent interpretation of mortality reduction across studies was difficult. In a metaanalysis published in 2019 [7], there was no difference in the survival of patients receiving standard medical support or MARS, but patients receiving high-intensity therapy with five or more MARS sessions showed better survival than those receiving low-intensity therapy with four or fewer sessions. Furthermore, a meta-analysis published in 2020 [15] Bleeding complications can also promote disseminated intravascular coagulation in patients with liver failure, making medical staff hesitant to proceed with liver transplantation.…”

“…Although it may be a good option for patients with end-stage liver failure [6], many clinicians are reluctant to apply MARS due to its high price, various side effects, and lack of evidence that it reduces mortality and improves survival rate [7][8][9]. Adverse effects of MARS include infection, hypotension, severe coagulopathy, bleeding, respiratory failure, cardiac failure, acute pancreatitis, severe thrombocytopenia, and seizure.…”