Extracorporeal blood detoxification by sorbents in treatment of hepatic encephalopathy.

Abstract

Extracorporeal blood detoxification by sorbent therapy long has been applied in treatment of hepatic failure and encephalopathy, starting with hemoperfusion columns and more recently with the currently marketed Liver Dialysis Unit. Liver Dialysis employs hemodiabsorption (dialysis of blood against powdered sorbents including charcoal and cation exchanger) to remove selectively numerous small-molecular-weight toxins of hepatic failure. Liver Dialysis is used in treatment of acute hepatic encephalopathy (AHE) because of decompensation of chronic liver disease (A-on-C) or fulminant hepatic failure (FHF). Controlled, prospective and randomized studies of daily 6-hour Liver Dialysis have shown physiologic and neurologic improvement of patients with AHE, regardless of etiology. Liver dialysis significantly improved the incidence of positive outcomes (recovery of hepatic function or improvement for transplant) of A-on-C patients versus controls (71.5% treated, and 35.7% control, P =.036), but had an insignificant improvement in outcome of patients with FHF as compared with the control group. Other extracorporeal sorbent devices are now in clinical testing phase. The molecular adsorbent regenerating system (MARS) device employs a polysulfone high-permeability dialyzer with albumin on the dialysate side to aid transfer of protein-bound toxins such as bilirubin and bile acids across the membranes. Sorbent columns of charcoal and an anion exchanger remove hepatic toxins from the albumin dialysate, and a second dialyzer removes water-soluble toxins, such as ammonium. Clinical results of daily MARS treatments of patients with hepatic failure are similar to that of Liver Dialysis, with neurologic and physical improvement occurs in most patients with AHE, and improved outcome for patients with A-on-C. The system extends the life of patients with hepatorenal syndrome. PF-Liver Dialysis is an experimental device combining hemodiabsorption with push-pull sorbent-based pheresis with powdered sorbent surrounding plasmafilters. PF-Liver Dialysis (Hemocleanse, Inc, W. Lafayette, IN) has been tested in a few patients with hepatic failure, grade 3-4 encephalopathy, and respiratory and kidney insufficiency. Treatments appeared to be safe and resulted in marked decreases in plasma levels of bilirubin, aromatic amino acids, ammonium, creatinine, and interleukin-1beta (IL-1beta). The PF add-on module adds the capability to Liver Dialysis to remove bilirubin, bile acids, and other strongly protein-bound toxins from treated patients and may be of clinical benefit in management of patients with the most severe hepatic failure and encephalopathy, including patients with FHF or concomitant sepsis.