Extracorporeal albumin dialysis for acute liver failure (interventional procedures consultation)

NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE

Interventional procedure consultation document

Extracorporeal albumin dialysis for acute liver failure

 

Acute liver failure is a life-threatening condition in which liver function suddenly and rapidly deteriorates. It can affect the ability of the blood to clot and reduce the oxygen supply to the brain, resulting in a sudden deterioration in mental functioning. Acute liver failure is most commonly caused by infection or poisoning following the use of prescription or recreational drugs, or alcohol.  

In extracorporeal albumin dialysis blood is pumped through a filter coated in albumin. The filtered blood is then pumped back into the body. The aim is to enable the patient to survive until the liver either repairs itself or is replaced by a transplanted donor liver.

 

The National Institute for Health and Clinical Excellence (NICE) is examining extracorporeal albumin dialysis for acute liver failure and will publish guidance on its safety and efficacy to the NHS in England, Wales, Scotland and Northern Ireland. NICE’s Interventional Procedures Advisory Committee has considered the available evidence and the views of Specialist Advisers, who are consultants with knowledge of the procedure. The Advisory Committee has made provisional recommendations about extracorporeal albumin dialysis for acute liver failure.

This document summarises the procedure and sets out the provisional recommendations made by the Advisory Committee. It has been prepared for public consultation. The Advisory Committee particularly welcomes:

  • comments on the provisional recommendations
  • the identification of factual inaccuracies
  • additional relevant evidence, with bibliographic references where possible.

Note that this document is not NICE’s formal guidance on this procedure. The recommendations are provisional and may change after consultation.

The process that NICE will follow after the consultation period ends is as follows.

  • The Advisory Committee will meet again to consider the original evidence and its provisional recommendations in the light of the comments received during consultation.
  • The Advisory Committee will then prepare draft guidance which will be the basis for NICE’s guidance on the use of the procedure in the NHS in England, Wales, Scotland and Northern Ireland.

For further details, see the Interventional Procedures Programme manual, which is available from the NICE website (www.nice.org.uk/ipprogrammemanual).

NICE is committed to promoting through its guidance race and disability equality and equality between men and women, and to eliminating all forms of discrimination. One of the ways we do this is by trying to involve as wide a range of people and interest groups as possible in the development of our guidance on interventional procedures. In particular, we aim to encourage people and organisations from groups in the population who might not normally comment on our guidance to do so. We also ask consultees to highlight any ways in which draft guidance fails to promote equality or tackle discrimination and give suggestions for how it might be improved. NICE reserves the right to summarise and edit comments received during consultations, or not to publish them at all, where in the reasonable opinion of NICE, the comments are voluminous, publication would be unlawful or publication would otherwise be inappropriate.

Closing date for comments: 24 June 2009

Target date for publication of guidance: September 2009

 

1     Provisional recommendations

1.1  The evidence on extracorporeal albumin dialysis for acute liver failure raises no major safety concerns. However, current evidence on its efficacy is inadequate in quality and quantity. Therefore, this procedure should only be used with special arrangements for clinical governance, consent and audit or research.

1.2  Clinicians wishing to undertake extracorporeal albumin dialysis for acute liver failure should take the following actions.

  • Inform the clinical governance leads in their Trusts.
  • Ensure that patients and their carers understand the uncertainty about the procedure’s efficacy and provide them with clear written information (subject to the requirement for an emergency procedure). In addition, the use of NICE’s information for patients (‘Understanding NICE guidance’) is recommended (available from www.nice.org.uk/IPGXXXpublicinfo). [[details to be completed at publication]]
  • Audit and review clinical outcomes of all patients having extracorporeal albumin dialysis for acute liver failure (see section 3.1).

1.3   NICE encourages further research into extracorporeal albumin dialysis for acute liver failure. This should describe clearly the indications for  treatment. Short and longer term survival and the numbers of patients ‘bridged to transplant’ should be documented and compared with standard treatments. Further information about the utility of biochemical markers to guide the frequency of treatment would be helpful. NICE may review the procedure on publication of further evidence.

 

2     The procedure

2.1   Indications and current treatments

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 or 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    Outline of the procedure

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 water-soluble toxins removed by haemodialysis. 

2.2.2  The blood is dialysed through a filter against an albumin-rich dialysate and toxic molecules bound to albumin in the blood are absorbed through the filter into 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, available at www.nice.org.uk/IP219aoverview

 

2.3     Efficacy

2.3.1  A meta-analysis of four randomised controlled trials (RCTs) and two non-randomised controlled studies that 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 three treatment groups (6/8 and 5/8 patients who had albumin dialysis by two 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). In the same study, no significant difference in 6-month survival following liver transplant was reported between treatment groups (94% [31/33] and 77% [20/26] patients survived, respectively) (p = 0.06).

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     Safety

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 two patients treated by albumin dialysis described severe pulmonary oedema in both patients. (Therapy was suspended in the second 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]). Haemorrhage from the catheter requiring a catheter position change occurred in 4% of treatments for fulminant hepatitis (absolute figures not stated).

2.4.4  The Specialist Advisers listed adverse events as increased variceal bleeding and infection. They considered theoretical adverse events to include coagulopathy, shock, hypotension, electrolyte abnormalities and thrombosis in the dialysis circuit.

 

3       Further information

3.1    This guidance requires that clinicians undertaking the procedure make special arrangements for audit. NICE has identified relevant audit criteria and is developing an audit tool (which is for use at local discretion), which will be available when the guidance is published.

3.2    This document is a review of NICE interventional procedures guidance 45 published in 2004. For more information and related NICE guidance see www.nice.org.uk.

 

Bruce Campbell

Chairman, Interventional Procedures Advisory Committee

May 2009

 

Personal data will not be posted on the NICE website. In accordance with the Data Protection Act names will be anonymised, other than in circumstances where explicit permission has been given.

 

It is the responsibility of consultees to accurately cite academic work in order that they can be validated.

This page was last updated: 30 March 2010