explaining the presently available criteria to define futility in liver transplantation and prposing future trends in the definition of 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
“ Medicine is powerless for
those who are overmastered
by their disease”

4. Futility in Liver transplantation
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
Sickest first 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
• Level of severity of an illness
• Initially conceptualised for allocation of nursing resources

10. Pre-transplant Acuity
Liver related + Liver unrelated illness

11. Organ involvement in Liver
disease

12. Framework to determine
futility
Transplant responsive
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 for high 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 UNOS data over 10 years
8% transplants for patients with MELD>40

17. • 1 year graft 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 septic shock
High cardiac risk score
Charlson co morbidity index>6
Predictors of higher
Futility

19. 10 times more
spending on patients
with MELD score >30

20. Acute on Chronic liver
failure
Dynamic category of liver failure associated with other organ
involvement

21. Acute on Chronic Liver
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 more organ failures
ACLF 3 on day 3-7
High chances
of futile transplant
Unfortunately 75% fall in this sub group

23. • French Multi centre 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 Chronic Liver
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
Non Paracetamol etiology
Higher death
on waiting list
Inotropes
Age>45
Use of high risk grafts
Predictors of
Futility

28. Age and Co morbidities
• 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 and Futility
• 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 co morbidity 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 (total psoas 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
• Porto pulmonary 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 to predict
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 to Transplant
• >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 reliable and 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 of co 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