Extracorporeal Detoxification for Hepatic Failure Using Molecular Adsorbent Recirculating System: Depurative Efficiency and Clinical Results in a Long‐Term Follow‐Up

Abstract

Acute liver failure and acute-on-chronic liver failure still show a poor prognosis. The molecular adsorbent recirculating system (MARS) has been extensively used as the most promising detoxifying therapy for patients with these conditions. Sixty-four patients with life-threatening liver failure were selected, and 269 MARS treatments were carried out as a bridge for orthotopic liver transplantation (OLT) or for liver function recovery. All patients were grouped according to the aim of MARS therapy. Group A consisted of 47 patients treated for liver function recovery (median age 59 years, range 23-82). Group B consisted of 11 patients on the waiting list who underwent OLT (median age 47 years, range 32-62). Group C consisted of 6 patients on the waiting list who did not undergo OLT (median age 45.5 years, range 36-54, P = 0.001). MARS depurative efficiency in terms of liver toxins, cytokines, and growth factors was assessed together with the clinical outcome of the patients during a 1-year follow-up. Total bilirubin reduction rate per session (RRs) for each MARS session was 23% (range 17-29); direct bilirubin RRs was 28% (21-35), and indirect bilirubin RRs was 8% (3-21). Ammonia RRs was 34% (12-86). Conjugated cholic acid RRs was 58% (48-61); chenodeoxycholic acid RRs was 34% (18-48). No differences were found between groups. Hepatocyte growth factor (HGF) values on starting MARS were 4.1 ng/mL (1.9-7.9) versus 7.9 ng/mL (3.2-14.1) at MARS end (P < 0.01). Cox regression analysis to determine the risk factors predicting patient outcomes showed that age, male gender, and Sequential Organ Failure Assessment score (but not Model for End-stage Liver Disease score) were factors predicting death, whereas the number of MARS sessions and the ΔHGF proved protective factors. Kaplan-Meier survival analysis was also used; after 12 months, 21.3% of patients in Group A survived, while 90.9% were alive in Group B and 16.7% in Group C (log rank = 0.002). In conclusion, MARS was clinically well tolerated by all patients and significantly reduced hepatic toxins. Better survival rates were linked to an OLT program, but patients' clinical characteristics on starting MARS therapy were the main factors predicting survival. The role of HGF should be evaluated in larger clinical trials.

Bioengineered transplantable porcine livers with re-endothelialized vasculature

“…This discrepancy between organ supply and demand results in thousands of deaths each year [www.unos.org]. Several treatment strategies are being developed to sustain critically ill patients until a time when a transplantable donor organ is available [1,2]. However, these therapies can only buy a small amount of additional time for patients in liver failure.…”

Removal of free light chains in hemodialysis patients without multiple myeloma: a crossover comparison of three different dialyzers

“…Albumin was assessed using the common laboratory method. The reduction rate per session (RRs) was calculated as follows [10]:

Fig. 1Study design

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Liver dialysis in acute-on-chronic liver failure: current and future perspectives

“…The effect of Prometheus on the cytokine concentration and markers of inflammation and liver regeneration was studied in 11 patients with ALF; it showed a significant decrease in the concentrations of TNFa, CRP, PCT and a(1) fetoprotein, but contrary to this, an increase in hepatocyte growth factor (HGF) was detected [42]. In another recent study by Donati et al of 64 patients treated with MARS for 269 treatment sessions given as a bridge for orthotopic liver transplantation (OLT) or for liver function recovery, MARS treatment was shown to reduce bilirubin and bile acids; however, HGF values showed a significant increase post-treatment from 4.1 ng/ml (1.9-7.9) to 7.9 ng/ ml (3.2-14) [43]. This is important because the HGF-Met pathway has been shown to play a critical role in promoting cell survival and regeneration of tissues as it suppresses and improves chronic inflammation and fibrosis [44].…”