Powdered Sorbent Liver Dialysis and Pheresis in Treatment of Hepatic Failure

Abstract

The Liver Dialysis Unit (the Unit) is a liver‐assist device that employs hemodiabsorption (dialysis of blood against powdered sorbents) to selectively remove numerous small molecular weight toxins of hepatic failure. The Unit has been cleared by the Food and Drug Administration and is indicated and marketed for treatment of acute hepatic encephalopathy (AHE) due to decompensation of chronic liver disease (A‐on‐C) or fulminant hepatic failure (FHF). Controlled, prospective, and randomized studies of liver dialysis were conducted at several centers, enrolling 56 patients with AHE, grades II–IV with or without renal and respiratory insufficiency or failure. Liver dialysis treatments were for 6 h daily, 1–5 days with similar observation periods for control patients. Physiologic status, neurologic status, and outcome (recovery of hepatic function, improvement for transplant, or death) were measured, and results were compared for treated patients versus controls for patients with A‐on‐C and patients with FHF. Liver dialysis resulted in 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, 35.7% control, p = 0.036), but had an insignificant improvement in the outcome of patients with FHF as compared with the control group. Among the overall 31 treated patients, 51.6% survived. Outcome was not negatively affected by the presence of kidney failure or respiratory failure. The plasmafilter unit (PF‐Unit) combines hemodiabsorption with push‐pull sorbent‐based pheresis (the PF add‐on module, with powdered sorbent surrounding plasmafilters). At blood flow rates of 200 ml/min, the system clears creatinine and aromatic amino acids at 120–160 ml/min, unconjugated bilirubin at 20–40 ml/min, and cytokines at 15–25 ml/min. The PF‐Unit has been tested in a few patients with hepatic failure with Grades III and IV encephalopathy, and respiratory, and kidney insufficiency. Treatment appeared to be safe, and there were no significant hematologic changes. Physiologic changes included improved blood pressure, and encephalopathy, and stable urine output. Chemical changes included a decrease in the plasma levels of bilirubin, aromatic amino acids, ammonium, creatinine, and IL‐1β. The PF add‐on module adds the capability to the Unit to remove bilirubin and other strongly protein‐bound toxins from treated patients and may be of clinical benefit in the management of patients with the most severe hepatic failure and encephalopathy, including patients with FHF or concomitant sepsis.

Artificial and bioartificial liver devices: present and future

“…A method for immobilising the powdered charcoal in a block is being evaluated for increased toxin binding capacity and better regeneration of dialysate 14 15. The next system should be able to support any type of hollow fibre (TUs 1 to 4).…”

Changes in cellular proliferation and plasma products are associated with liver failure

“…The elevated levels of circulating IL-6 and TNFα, also described by others[42,43], have been related to attempts at liver regeneration[44,45] and liver injury[46], respectively. Therapeutic approaches targeting the clearance of inflammatory/toxic products (plasmapheresis, hemodiafiltration, and bioartificial livers) from the liver or anti-cytokine therapy are currently being considered[42,47-49] despite contradictory clinical results[50,51]. …”

What Is the Role of Renal Replacement Therapy in the Intensive Care Unit?

“…Experimental approaches have included hemodiabsorption 44 and the molecular adsorbent recirculating system (MARS). 45,46 Small studies using these techniques in the management of hepatic failure showed benefit in patients with acute-on-chronic hepatic failure, 44 the hepatorenal syndrome, 45 and even fulminant hepatic failure. 46 In the absence of more robust evidence to confirm these findings, however, no recommendation can be given to support their routine use in clinical practice.…”