Removal of albumin bound toxins by albumin dialysis improves clinical course of liver cirrhosis complicated by severe cholestasis

Background: Liver Cirrhosis complicated by severe cholestasis (bilirubin > 20 mg/dl) is associated with accumulation of toxic albumin bound substances, like lipophilic bile acids, bilirubin, tryptophane and its metabolites, endogenous vasodilatators like Nitric oxide, prostaglandins, neurotoxins like endogenous benzodiazepines etc. Elevated levels of these substances exhibit toxic effects or/and increase the unbound fraction of other, usually albumin bound toxins, thus creating a cumulative toxic effect on the brain, the kidneys, the cardiovascular system and the liver itself.

A new extracorporeal dialysis using a specific membrane and a dialysate solution containing albumin as a Molecular Adsorbent that is on line Recycled by a sorbent System (MARS) has been introduced as a method to remove these toxins from blood. Several studies suggested a positive effect of this method on mental, liver, renal and vascular function.

Method: In order to show whether this treatment supports recovery of decompensated liver function if cirrhosis is complicated by cholestasis a prospective study was performed including 26 patients in an uncontrolled (phase I) and 24 patients in a controlled (phase II) study.

Patients representing liver cirrhosis (at least CTP score equivalent to B) and intrahepatic cholestasis with bilirubin > 20 mg/dl where recruited.

An 6-8 hours treatment with the MARS-device was applied every day (up to a maximum of 10 treatments) as long the bilirubin level was above 15 mg/dl in the therapy group.

A recovery of excretory liver function defined by spontaneous drop of bilirubin below 15 mg/dl for at least three days without further extracorporeal treatment was the aim of the treatment.

Results: In total, 38 (26 in phase I and 12 in phase II) patients in total where treated with the MARS procedure in both trials, 12 patients (phase II) received Standard Medical Therapy alone.

In the phase I trial, a significant improvement of CTP-Score could be observed in the treated population that was not caused primarily by the reduction of bilirubin, but was caused by disappearance of ascites, and improvement of hepatic encephalopathy, coagulation status and serum albumin level. In the second step, these data could be confirmed by a prospective controlled trial.

Conclusion: Albumin dialysis is a save and effective treatment to remove albumin bound toxins in liver cirrhosis complicated by cholestasis. This is associated by an improvement of the clinical course of these patients as shown by uncontrolled and confirmed by controlled clinical studies.