2 The procedure
2.1.1 In acute liver failure there is rapid deterioration of liver function. It has a high mortality rate. Causes include poisoning due to alcohol, pharmaceutical or recreational drugs and viral infection. Less common causes are metabolic disease and acute fatty liver of pregnancy.
2.1.2 There are few treatment options for patients with diminishing liver function. Some patients recover liver function with supportive medical therapy including haemodialysis/filtration. Other patients need transplantation. However, there is a shortage of donor livers.
2.2.1 This procedure aims to support the patient until either their own liver function recovers or a transplant becomes available. The procedure removes toxins bound to albumin in the blood in addition to the water-soluble toxins that can be removed by haemodialysis.
2.2.2 The blood is dialysed through a membrane against an albumin-rich dialysate. Toxic molecules bound to albumin in the blood pass through the membrane and bind onto the albumin molecules of the dialysate. The dialysate is then passed through an activated charcoal and an anion-exchange resin column (to remove toxins bound to albumin) and through a conventional filter (to remove water-soluble toxins). The dialysate is thus regenerated, and can be recirculated against the patient's blood.
2.2.3 A number of different systems are available for this procedure.
Sections 2.3 and 2.4 describe efficacy and safety outcomes from the published literature that the Committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the overview.
2.3.1 A meta-analysis of 4 randomised controlled trials (RCTs) and 2 non-randomised controlled studies, which included 128 patients in total, reported no significant difference in 30-day all-cause mortality between patients who had extracorporeal albumin dialysis and those who had standard medical treatment (relative risk [RR] 0.56; 95% confidence interval [CI] 0.28 to 1.14; p = 0.11). No significant differences in mortality were reported between treatment groups in the subgroups of patients with acute-on-chronic liver failure (RR 0.49; 95% CI 0.12 to 2.17; p = 0.35) or those with acute liver failure (RR 0.49; 95% CI 0.15 to 1.58; p = 0.23).
2.3.2 An RCT of 24 patients with cirrhosis of the liver treated by albumin dialysis or standard haemodialysis reported no significant difference in 6-month survival between 3 treatment groups (6/8 and 5/8 patients who had albumin dialysis by 2 different systems, and 3/6 patients who had standard haemodialysis, survived) (p = 0.40).
2.3.3 A non-randomised controlled trial of 79 patients with acute alcoholic liver disease reported that survival at 3-year follow-up was significantly greater after extracorporeal albumin dialysis (52% [17/33]) than after standard medical therapy (17% [8/46]) (p = 0.0035). A non-randomised controlled trial of 159 patients reported no significant difference in overall survival at 6-month follow-up between patients treated by extracorporeal albumin dialysis (75% [85/113]) and patients treated with standard medical therapy (61% [28/46]) (p = 0.07).
2.3.4 The Specialist Advisers listed key efficacy outcomes as survival or successful bridge to transplant, reduced intracranial pressure/encephalopathy and improved haemodynamic stability.
2.4.1 A case series of 30 patients reported that 30% (9/30) of patients developed positive blood cultures 2–17 days after extracorporeal albumin dialysis treatment. All 9 patients died.
2.4.2 A case report of 2 patients treated by albumin dialysis described severe pulmonary oedema in both patients. (Therapy was suspended in 1 patient.) In both patients the oedema resolved within 24 hours of aggressive medical treatment. One patient died at 9 days and the other at 201 days of follow-up.
2.4.3 A case series of 191 patients treated by 2027 extracorporeal albumin dialysis sessions reported transitory hypotension in 14% (292/2027) of treatments. Transitory hypoglycaemia requiring medical management occurred in 17% (335/2027) of treatments, all in patients with Model for End-stage Liver Disease (MELD) scores of 30–40 (MELD scores range from 1 [least severe] to 40 [most severe]).
2.4.4 The Specialist Advisers listed adverse events as increased variceal bleeding and infection. They considered theoretical adverse events to include coagulopathy, shock, electrolyte abnormalities and thrombosis in the dialysis circuit.