Liver units – any better than your place? by Dr Mary Pinder
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1) Liver units may provide better outcomes than general hospitals for some patients with acute or chronic liver failure through multi-disciplinary expertise, advanced treatment strategies like transplantation and extracorporeal support, and high quality supportive care. 2) However, evidence for benefits of extracorporeal liver support systems is limited and they may only help select patient groups. 3) Whether liver units are better likely depends on the individual patient's characteristics and severity of liver disease. Early discussion with liver transplant centers is still recommended.
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Liver units – any better than your place? by Dr Mary Pinder
- 1. LIVER UNITS - ANY BETTER THAN YOUR PLACE? Mary Pinder Sir Charles Gardner Hospital Perth WA
- 5. Liver Units - any better than your place? • Supportive evidence • Extrapolation from other specialty areas • Advanced treatment strategies
- 7. Liver Units better? - YES • Supportive evidence • Extrapolation from other specialty areas • Advanced treatment strategies
- 8. Acute Liver Failure (IIa) Paracetamol Encephalopathy pH < 7.4 Lactate >2.5 mmol/L Non-paracetamol Encephalopathy Coagulopathy AKI Additional organ failure Chronic Liver Failure Decompensated (IIa) Recurrent refractory encephalopathy (1-C) Hepatopulmonary syndrome (I-B)
- 10. Discuss with a Liver Tx Unit: • Coagulopathy • Acute kidney injury • Persisting acidosis • Hypotension • Hypoglycaemia • Severe thrombocytopaenia • Encephalopathy • Any concerns MJA 2015
- 11. Liver Units better? - YES • Supportive evidence • Extrapolation from other specialty areas • Advanced treatment strategies
- 15. Ian Tweedie Neuroanaesthesiol Crit Care 2016;3:62-5
- 16. Liver Units better? - YES • Supportive evidence • Extrapolation from other specialty areas • Advanced treatment strategies
- 17. Advanced Treatment Strategies • Liver transplantation • Extracorporeal support
- 18. Liver transplantation • Definitive treatment • Multi-disciplinary expertise • Centralised service
- 19. 96% @ 1 year 71% @ 10 years
- 20. Extracorporeal Support BIOARTIFICIAL SYSTEMS ARTIFICIAL SYSTEMS HYBRID SYSTEMS Extracorporeal Liver Assist Device (ELAD) Single Pass Albumin Dialysis (SPAD) Hepat-Assist Bioartificial Liver Support System (BLSS) Molecular Adsorbent Recirculating System (MARS) TECA Hybrid Liver Artificial Support System Radial Flow Bioreactor (RFB) Fractionated Plasma Separation & Adsorption (FPSA) “Prometheus” Modular Extracorporeal Liver Support (MELS) Bioartificial Liver (AMC-BAL) Selective Plasma Filtration Therapy (SEPET)
- 21. Extracorporeal Support BIOARTIFICIAL SYSTEMS ARTIFICIAL SYSTEMS HYBRID SYSTEMS Extracorporeal Liver Assist Device (ELAD) Single Pass Albumin Dialysis (SPAD) Hepat-Assist Bioartificial Liver Support System (BLSS) Molecular Adsorbent Recirculating System (MARS) TECA Hybrid Liver Artificial Support System Radial Flow Bioreactor (RFB) Fractionated Plasma Separation & Adsorption (FPSA) “Prometheus” Modular Extracorporeal Liver Support (MELS) Bioartificial Liver (AMC-BAL) Selective Plasma Filtration Therapy (SEPET) Molecular Adsorbent Recirculating System (MARS)
- 22. Extracorporeal Support BIOARTIFICIAL SYSTEMS ARTIFICIAL SYSTEMS HYBRID SYSTEMS Extracorporeal Liver Assist Device (ELAD) Single Pass Albumin Dialysis (SPAD) Hepat-Assist Bioartificial Liver Support System (BLSS) Molecular Adsorbent Recirculating System (MARS) TECA Hybrid Liver Artificial Support System Radial Flow Bioreactor (RFB) Fractionated Plasma Separation & Adsorption (FPSA) “Prometheus” Modular Extracorporeal Liver Support (MELS) Bioartificial Liver (AMC-BAL) Selective Plasma Filtration Therapy (SEPET) Molecular Adsorbent Recirculating System (MARS)
- 23. Extracorporeal Support BIOARTIFICIAL SYSTEMS ARTIFICIAL SYSTEMS HYBRID SYSTEMS Extracorporeal Liver Assist Device (ELAD) Single Pass Albumin Dialysis (SPAD) Hepat-Assist Bioartificial Liver Support System (BLSS) Molecular Adsorbent Recirculating System (MARS) TECA Hybrid Liver Artificial Support System Radial Flow Bioreactor (RFB) Fractionated Plasma Separation & Adsorption (FPSA) “Prometheus” Modular Extracorporeal Liver Support (MELS) Bioartificial Liver (AMC-BAL) Selective Plasma Filtration Therapy (SEPET) Extracorporeal Liver Assist Device (ELAD)
- 25. VTI-208 Trial • ELAD in alcohol induced liver decompensation (AILD) • Phase 3 multi-centre, randomised, open label • 203 patients during 2013-2015 @ 40 sites 96 ELAD 107 Control
- 26. Secondary Endpoints Proportion of Survivors ELAD Control P-Value 28 days 76% 80.4% 0.46 91 days 59.4% 61.7% 0.74 VTI-208 Results
- 27. VTI-208 Results Combined sub-group analysis Age <50 yr, MELD <30, INR <2.5, Creatinine <115 umol/L, Bilirubin <275 umol/L
- 28. VTI-208 Conclusions • ELAD failed to meet primary and secondary end-points • Sub-group analysis showed: • Improved survival on ELAD v control with: • Lower MELD (<28) • Younger age (<47 years) • Poor outcome on ELAD v control with: • AKI • Coagulopathy
- 29. Liver Units better? - YES • Multi-disciplinary expertise • Liver transplant service • Fancy-schmancy treatment strategies • Guidelines recommend early discussion
- 31. Liver Units better? - NO • Supportive evidence • Extrapolation from other specialty areas • Advanced treatment strategies
- 34. “… more what you’d call ‘guidelines’ than actual rules”
- 35. Liver Units better? - NO • Supportive evidence • Extrapolation from other specialty areas • Advanced treatment strategies
- 36. Ian Tweedie Neuroanaesthesiol Crit Care 2016;3:62-5
- 38. Liver Units better? - NO • Supportive evidence • Extrapolation from other specialty areas • Advanced treatment strategies
- 39. Secondary Endpoints Proportion of Survivors ELAD Control P-Value 28 days 76% 80.4% 0.46 91 days 59.4% 61.7% 0.74 VTI-208 Results Advanced treatment strategies don’t work!
- 40. VTI-208 Conclusions • ELAD failed to meet primary and secondary end-points • Sub-group analysis showed: • Improved survival on ELAD v control with: • Lower MELD (<28) • Younger age (<47 years) • Poor outcome on ELAD v control with: • AKI • Coagulopathy
- 41. Liver Units better? - NO • Outcome data for cirrhotics comparable • Extra-corporeal liver support systems no benefit
- 43. Ian Tweedie Neuroanaesthesiol Crit Care 2016;3:62-5
- 44. VTI-208 Results Combined sub-group analysis Age <50 yr, MELD <30, INR <2.5, Creatinine <115 umol/L, Bilirubin <275 umol/L Advanced treatment strategies may work in selected cases
- 45. Liver failure and critical care • Specific challenges for patient management • Who and when to refer to specialist centres • Tyranny of distance
- 46. Adult Liver Units in ANZ Population ~28 million
- 47. UK Population ~ 65 million
- 49. Liver Units - Any better than your place? YES NO MAYBE Tranplant services Extra-corporeal support Multi-disciplinary expertise High quality supportive care Up-skilling of non-liver units Consensus guidelines for referral & transfer
Notes de l'éditeur
- Thank you to Deepak and the conference committee for inviting me to speak. Before I start I’d like to state that I have no financial conflicts but I do work in a liver unit
- If I was talking about this liver unit - a world leader in management of the critically ill liver patient, the answer would be clearly a resounding yes and there would be no contest but I’m going to look at it from the perspective of my unit which is much lower key and although in this photo looks as though it has been touched by heaven, the comparison with KCH is more like this
- If I was talking about this liver unit, the answer would be clearly a resounding yes and there would be no contest but I’m going to look at it from the perspective of my unit which is much lower key and although in this photo looks as though it has been touched by heaven, the comparison with KCH is more like this
- So are liver units any better than your place? Well this style of topic is usually done at conferences as a robust debate and firstly I hope we reach a better conclusion than the US voters and secondly I don’t have a sparring partner so I’ll have to argue for both sides
- So back to the debate, my arguments for yes and no are going to centre round the available evidence, extrapolation from other specialty areas and the practicalities of advanced treatment strategies
- Evidence is a bit sparse and so I’ve turned to guidelines and recommendations No Cochrane review, no head to head outcome studies but if we look at guidelines on management of liver failure they all include criteria for when to refer to a liver unit
- Written from the toxicology stand-point and includes guidelines on when to refer Geoff Isbister - one of the authors - is talking tomorrow morning on how to kill your liver
- Good evidence for centralisation of services including that relating to trauma management, paediatric and neurocritical care. In the interests of time I will just look at neurocritical care
- Good evidence for centralisation of services including that relating to trauma management, paediatric and neurocritical care. In the interests of time I will just look at neurocritical care
- Good evidence for centralisation of services including that relating to trauma management, paediatric and neurocritical care. In the interests of time I will just look at neurocritical care
- >80000 procedures world-wide over the last 50 years Approx 270 /year in ANZ
- 96% at one year and 71% at 10 year
- Bastard child of renal replacement therapy and ECMO
- OK so definitely some things that non-liver units can’t do So can we say liver units are better - well let’s look at the opposing view
- So lets look at the counter argument
- Studies report outcomes for cirrhotic patients admitted to ICU in Transplant centres to be 6mth and 12 mth mortality rates of 60% and 80% respectively with similar or better rates reported from non-transplant units although you would expect transplant centres to see sicker patients, further on in their disease process with more other organ dysfunction and less reserve
- Captain Barbossa - the recognised authority of evidence based practice Guidelines schmidelines
- OK so definitely some things that non-liver units can’t do So can we say liver units are better - well
- the optimal model may be a neuro ICU pod in a general ICU co-located with a neuroscience centre so a compromise between a specialist neuro ICU and a general non-specialist ICU
- If we look at the status of ICU in ANZ, it is dynamic and over time units increase in size and complexity of case mix. The H1N1 pandemic in 2009 was a turning point and is a good example of how we rose to the challenge and units that had previously limited experience of ECMO, driven by need took this on and did a pretty good job. And the cornerstone of management in liver failure is high-quality organ support and attention to detail. We need clear guidelines for referral and dynamic biomarkers may give a better indication of severity and prognosis Prevalence of cirrhosis is increasing and this is compounded in ANZ by the tyranny of distance
- ANZ population combined approx 28 million
- ANZ population combined approx 28 million UK 64 million