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18th ISAD

International Symposium on Albumin Dialysis

New outcome data on late stage organ support with albumin dialysis

Background: 
Among different extracorporeal liver support systems, MARS® therapy belongs to the most studied methods in patients with liver failure with a proved beneficial effect on hepatic encephalopathy (HE), hepatorenal syndrome (HRS) or hyperbilirubinemia. However, a general survival advantage of any liver support for liver failure has not been shown yet and is restricted to meta-analyses or patient subgroups.

Aims: 
We studied the effects of MARS® therapy compared to standard medical treatment (SMT) in three separate patient cohorts, namely, in patients presented with acute-on-chronic liver failure (ACLF), acute liver injury (ALI) and in those with graft dysfunction (GD).

Methods: 
We report on our experience over a 6.5 year period in patients with severe hepatic injury treated at the Medical Department of the University Hospital Muenster (Germany). 101 patients with ACLF (grade 1-3, CLIF-C-OF liver subscore=3) were identified and received either standard medical treatment (SMT, n=54) or SMT and MARS® (n=47). Second, the results of this retrospective analysis in ACLF-patients were tested against the RELIEF trial. In addition, 53 patients suffered from ALI of the native liver without a preexisting liver disease (SMT n = 31, MARS® n = 22) and 20 patients showed a severe GD after liver transplantation (SMT n = 10, MARS® n = 10) and were included in this retrospective analysis.

Results: 
In all patient subgroups laboratory parameters (bilirubin and creatinine) improved by MARS® therapy independent of the underlying etiology. Additionally, in ACLF patients the short-term mortality (up to day 14) of the MARS® group was significantly reduced compared with SMT. Resulting in a reduced 14-day mortality rate in the MARS® group (9.5% vs. 50.0% with SMT, p=0.004), especially in patients with multi-organ failure (ACLF grade 2-3). Concerning the affected organ system, this effect of MARS® on mortality was particularly evident among patients with increased kidney, brain or coagulation CLIF-C-OF subscores. Subsequent reanalysis of the RELIEF dataset with adoption of the CLIF-classification resulted in similar findings. Concerning ALI and severe GD, no differences in 28-day mortality were observed in acute liver injury (MARS® 5.3% [95%CI: 0 - 15.3]; SMT 3.3% [95% CI: 0 – 9.8], p = 0.754) and GD (MARS® 20.0% [95% CI: 0 – 44.7], SMT 11.1% [95% CI: 0 – 31.7], p = 0.478). However, MARS® improved the patients’ bilirubin values for the short term compared to SMT alone. In patients with ALI, this response sustained even after end of MARS® therapy. Contrary, majority of patients with GD and initial response to MARS® therapy worsened in hyperbilirubinemia.

Conclusions: 
MARS® treatment was associated with an improved short-term survival of patients with ACLF and multi-organ failure. Among these high-risk patients, MARS® treatment might bridge to liver recovery or liver transplantation. Although not improving 28-day mortality, MARS® therapy increased short-term response in patients with ALI as well as with GD. Especially in acute hepatic injury, use of MARS® therapy resulted in a sustained stabilization of the liver function and improved liver regeneration. It might be hypothesized that short-term response to MARS® predicts further course of disease. Decisive for a successful therapy is the exact indication of the respective liver dialysis procedure for this very heterogeneous disease. Future studies are needed to define more accurate patient selection criteria for MARS® therapy.

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