Development of reliable artificial liver support (ALS)-plasma exchange in combination with hemodiafiltration using high-performance membranes

Abstract

A new artificial liver support system (ALSS) consisting of plasma exchange (PE) in combination with hemodiafiltration (HDF) using high-performance membranes of polymethyl methacrylate (PMMA) and cellulose triacetate (CTA) was developed to efficiently remove middle molecules from plasma and treat fulminant hepatic failure (FHF) complicated by the onset of hepatic coma. Twenty-seven patients with FHF due to viral hepatitis, two with type A (HA), nine with type B (HB), and 16 with type non-A, non-B (NANB) underwent therapy with this new ALSS over the last five years. Three patients with an exacerbation of chronic HB and 15/16 with type NANB hepatitis were treated with interferon (IFN) also. Of these, 25 patients (92.6%) regained consciousness and 15 (55.6%) [1/2 (50%) with type A, 6/9 (66.7%) with type B and 8/16 (50%) with type NANB hepatitis] survived. Including four patients who survived with intensive care and plasma exchange alone, 19/31 (61.3%) patients survived. Because of its biocompatibility, both survivors and nonsurvivors could be sustained with the ALSS without complications for long periods (19.3 days for the survivors and 32.4 days for nonsurvivors). With this ALSS the ability to sustain life for such prolonged periods allows hepatic regeneration to occur and result in patient survival. It is anticipated that this new ALSS will not only be of value in cases of fulminant hepatic failure but that it may also play a role in sustaining life for those awaiting liver transplantation.

Use of Sorbent Columns and Haemofiltration in Fulminant Hepatic Failure

“…Improvement in conscious level was observed in 8 patients, but only 3 sur vived, with no evidence of liver regeneration in those that died [11], Significant removal of middle molecules was observed in the filtrate. Better results for survival were obtained by Yoshiba et al [12], who used either a poly methylmethacrylate or cellulose triacetate membrane. In a recent case report from the same group, 30-35 liters of fluid were removed per day using a polyacrylonitrile filter with ace tate Ringer's replacement fluid, together with a 2.5-to 3-litre plasma exchange per day [13].…”

HBV-related fulminant hepatic failure: successful intensive medical therapy in a candidate for liver transplantation

“…No single therapy can save the life of a patient with FHF. First of all, we introduced the high-volume hemodiafiltration combined with plasma exchange (high volume HDF-PE) developed by Yoshiba et al 6 With this, we were able to keep the patient alert and reduce the need for artificial respiratory support and sedation.…”

Review of Support Systems Used in the Management of Fulminant Hepatic Failure

“…Hémodiafil tration is hemofiltration using an acetate buffer or some other dialysate, thus allowing removal of fluid and low-to-middle molecular weight solutes more effectively. An initial study by Yoshiba et al [45] was successful in treating 15 of 27 patients in stage I to IV FHF. Early pilot studies using combinations of support systems have been encouraging, but further investiga tions are needed to prove efficacy.…”

“…Other combination therapy has included the treatment of 2 patients using charcoal hemoperfusion with hemodialysis, and the treatment of 1 patient with contin uous hemoperfusion with plasma exchange [42,43], A combination of hemodialysis and char coal and resin absorption of dialysate (called hemodiabsorption) was successfully used to treat 2 of 5 patients until a donor liver organ was available for transplantation or until liver function recovered [44], This system removed molecules of a molecular weight of 100 or more for many hours without saturation. Yoshiba et al [45] used a combination of plasma exchange and hémodiafiltration. Hémodiafil tration is hemofiltration using an acetate buffer or some other dialysate, thus allowing removal of fluid and low-to-middle molecular weight solutes more effectively.…”