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Futility in liver transplantation
- 1. Futility In Liver Transplantation Dr.Abhishek Yadav Senior consultant GI and Liver Transplantation VPS Lakeshore Hospital Kochi
- 2. Real life Scenario •18 year female patient with Acute liver failure • Referred to us on day 4, worsening mentation- intubated at presentation • Lactate- 10 , on noradrenaline • Family initially reluctant for transplantation • Day 6- Ventilated, hemodynamicaly stable ( 2 inotropes), no sepsis, renal shut down—>requiring CRRT • Family now wants to proceed with a transplantation Is there a reasonable chance of survival with transplantation OR Will the transplantation be Futile?
- 3. Medical Futility “ Medicineis powerless for those who are overmastered by their disease”
- 4. Futility in Livertransplantation Definitions • Rana et al 2008- Post transplant mortality>wait list mortality • Lao et al 2010- One year mortality • Petrowsky et al 2014- 90 day or in-hospital mortality • Asrani et al 2015- >50% at 5 years
- 5. General definitions of Futility •Physiological futility- Transplant very early/very sick patients • Imminent disease futility- Failure of life support pre transplant • Lethal condition futility- Advanced HCC • Qualitative futility- Failure to thrive/ brain injury in ALF
- 6. Ethics of Futility •Related to allocation of scarce resources • Is it relevant to LDLT? Equity vs Efficiency
- 7. Equity vs Efficiency Equity Sickestfirst policy MELD MELD NA PELD Share 35 Patient gets preference over “nameless faces”
- 8. Equity vs Efficiency Efficiency • Organs allocated where they can be utilised efficiently • Kidney allocation model/exclude high risk transplants • Single patient benefit OR greatest benefit to aggregate of patients • Medical and ethical challenge
- 9. Medical acuity • Levelof severity of an illness • Initially conceptualised for allocation of nursing resources
- 10. Pre-transplant Acuity Liver related+ Liver unrelated illness
- 11. Organ involvement inLiver disease
- 12. Framework to determine futility Transplantresponsive conditions Encephalopathy Ascites Coagulopathy Scoring systems Transplant Non Responsive conditions CAD COPD Sarcopenia Older age
- 13. Framework to determine futility •a Most patients belong here
- 14. Scenarios • Transplantation forhigh MELD patients - MELD>40 • Transplantation in ACLF • Transplantation in ALF • Age and Co-morbidities • Frailty and Sarcopenia • Pulmonary conditions - PPH, HPS
- 15. Transplantation for MELD >40 •MELD score was introduced in 2002 as an allocation score • Not an outcomes assessment tool • Most evidence suggests worse outcomes and higher resource utilisation • Is transplanting these patients worth it? • Which subset predicts futility?
- 16. Analysis of UNOSdata over 10 years 8% transplants for patients with MELD>40
- 17. • 1 yeargraft and patient survival 77 and 66% respectively • Significantly lower than lower MELD cohorts • Futile transplants ( 3 month mortality) were 2 times more than MELD<30 cohort • Futility predictors- Age >60, obesity, pre transplant ventilation, multiple co-morbidities
- 18. Pre transplant septicshock High cardiac risk score Charlson co morbidity index>6 Predictors of higher Futility
- 19. 10 times more spendingon patients with MELD score >30
- 20. Acute on Chronicliver failure Dynamic category of liver failure associated with other organ involvement
- 21. Acute on ChronicLiver Failure • Evolution of illness is dynamic • Clinical course between day 3-7 is crucial • Therefore these patients have a narrow window of opportunity for transplantation • Results of transplantation are dependent on other organ systems involvement
- 22. 4 or moreorgan failures ACLF 3 on day 3-7 High chances of futile transplant Unfortunately 75% fall in this sub group
- 23. • French Multicentre study • Transplantation for ACLF -3 • Results similar to ACLF1,2 • Higher post transplant complications • Better post transplant care/ centre experience • Shorter pre transplant ICU stay—> early referral!
- 24. Acute on ChronicLiver Failure • Early listing for transplantation • De- listing should be dynamic • Ongoing GI bleed, sepsis control <24 hours definite contra indications • Subjective parameters cannot be neglected • Centre experience plays a major role in outcomes
- 25. Acute Liver Failure •Accounts for 10-15% of transplants world wide • Results of transplantation worse than other indications • Well defined listing criteria King’s college criteria etc • Few guidelines to guide when not to transplant other than irreversible brain injury
- 26. 3 risk factors-30% 90 day mortality 4 risk factors- 50% 90 day mortality
- 27. Inotropes RRT Blood group non-A NonParacetamol etiology Higher death on waiting list Inotropes Age>45 Use of high risk grafts Predictors of Futility
- 28. Age and Comorbidities • Increasingly geriatric population being listed for transplantation • 5% in the UNOS database >70 years • Marginally lower survival when age adjusted for co morbidities • No defined age cut off • Most centres would not list above 75 years
- 29. Co Morbidities andFutility • Few studies have evaluated the effects of co morbidities on results of transplantation • Though individual diseases might not affect the outcomes • A combination of co morbidities might be ominous —> the concept of multiplication of risk factors
- 30. • Charlson comorbidity index- score of 9 co-morbidities • 5 diseases were significantly associated with outcomes
- 31. Physical Frailty and Outcomes •Frailty originates from geriatric practise • Biological syndrome leading to increased vulnerability • Co-morbidity is a risk factor for frailty • Fried frailty index, six minute walk test, frailty index—> scores for frailty • Frail patients have a low reserve to tolerate complications —> Sepsis, delayed graft function etc.
- 32. Sarcopenia and outcomes •Effect of liver disease on sarcopenia is well described • Gut- Liver axis and Liver-muscle axis are gaining interest • Sarcopenia is a good morphological correlate to frailty • Hand grip strength, stair climb power test, six minute walk distance, CT scan, bio electric impedance - Measures of sarcopenia • BMI, skin fold thickness unreliable because of fluid retention
- 33. • TPA (totalpsoas area)- area of the psoas muscles measured at L3-4 level • Psoas muscle area has been shown to have a direct relationship with sarcopenia and poor outcomes after transplantation
- 34. Pulmonary complications • Hepato-pulmonary syndrome • 15-30% prevalence • PaO2 <70, intra pulmonary shunts • No correlation with severity of liver diseases • No evidence of poor post transplant outcomes
- 35. Pulmonary Complications • Portopulmonary hypertension • mPAP>25, PVR >240 dynes/cm, pawp<15mm hg • Mild-mPAP 25-35; Moderate-mPAP 35-45; Severe- mPAP >45 • Reversibility with transplantation unpredictable • High peri operative mortality • High futility when unresponsive to medical management
- 36. Scoring systems topredict futility • Numerous complex scores have been proposed to predict outcomes • Balance of Risk ( BAR) score
- 37. • SOFT score-survival outcomes after liver transplantation • p-SOFT score • None of these have been validate
- 38. Too Sick toTransplant • >4 organ failure (liver, kidney, lungs, circulation, brain) • Brain oedema and herniation • Circulatory failure>vasopressors with limited responsiveness • Severe PPH • Maximal ventilatory support/ECMO • Infection- bacteraemia/ fungaemia, septic shock, active SBP
- 39. Conclusions • No reliableand validated de-listing criteria exist • Very small window of opportunity to transplant in ALF and ACLF • Transplant non-responsive conditions should weigh heavy in decision making • High MELD patients entail higher resources and complications • Extra hepatic system involvement determines success in transplantation for ACLF
- 40. Conclusions • Combination ofco morbidities could determine futility • Frailty and Sarcopenia are often neglected in decision making • There will always be an element of subjectivity • Criteria shift with individual and centre experience