Contraindications for liver transplant surgery Futility and fraility in liver transplant

1. Contraindications to LTx –
Futility and Fraility
By - Dr. Rohit K. Saini
Moderator – Dr. Karthik P.

2. Contraindications
●Severe Cardiopulmonary disease
●AIDS
●Active extrahepatic malignancy
●HCC with extrahepatic metastases
●Anatomic abnormalities that preclude transplantation
●Active and uncontrolled sepsis
●Active substance or alcohol abuse
●Persistent nonadherence with medical care
●Lack of adequate social support

3. Relative C/I
• Advanced age
• HIV
• Obesity
• Portal vein thrombosis
• Cholangiocarcinoma
• Prior complex hepatobiliary surgery
• Previous malignancy
• Moderate to severe pulmonary hypertension

4. Allocation
• Initially LT prioritisation was based on waiting time
• Increased waiting list mortality
• MELD score introduced (2002) – Better prediction
• MELD-based allocation is the most commonly
applied worldwide

6. • MELD is excellent for determining wait-list mortality,
• Study - 2 groups (MELD >40 vs MELD <40)
• ICU stay and hospital stay were longer after LT for
MELD >40
• but survival post-LT, was not different between the
groups (P = 0.59)
Cardoso FS, Postoperative resource utilization and survival among liver
transplant recipients with model for end-stage liver disease score ≥ 40: a
retrospective cohort study. Can J Gastroenterol Hepatol. 2015

7. Shortage of donor livers - dilemma between ‘‘equity‘‘ and
‘‘efficiency’’.

8. Terms
• Too sick for transplant
• Futility
• Potentially inappropriate

9. Futility
• The Hippocratic Corpus
• medicine is powerless who are overmastered by
their diseases
• suggests withhold treatment.

10. Definitions of futility

11. Risk Models
• Estimate benefit vs no benefit from LT,
• predict the likelihood of inappropriate LT
• Predicts post LTx outcome

13. P- SOFT and SOFT
3-month survival :
<5 points - 97%, (low risk)
6–15 points - 94%, (low to moderate)
16–35 points - 84%, (mod to high)
36–40 points - 62%, (high risk)
>40 points – 38% (futile)
Rana A et al. Survival outcomes following liver transplantation (SOFT) score: a novel method to predict
patient survival following liver transplantation. Am J Transplant. 2008

15. UCLA Score
• 4 independent
predictors:
1. MELD ≥40
2. Cardiac risk - any one:
• severe valvular disease,
• CAD with > 70% stenosis
or previous PCI,
• H/O MI,
• H/O arrhythmias,
• elevated pre-LT trop I
(>0.2 ng/ml),
• new RWMA on 2D Echo.
3. Age adjusted Charlson
comorbidity index (CCI)
≥6.
4. Preoperative septic shock:
• defined as positive
cultures requiring IV
antibiotic treatment,
• infection-induced
systemic hypotension
requiring vasopressors,
and
• ICU management.
Petrowsky H et al. Liver transplantation in highest acuity recipients: identifying
factors to avoid futility. Ann Surg. 2014

17. UCLA Score
• Using all 4 factors, the futility prediction (c-statistic)
is 0.754.
• Score of ≥26 - high futility risk (50% mortality) at 3
months after OLT,
• Scores of ≤22 - excellent 3-month survival rate of
93%

18. ALF
As multiorgan failure develops rapidly (short window), the
decision to be taken in a timely manner, to avoid poor outcomes.

19. Criteria’s

20. King’s College Hospital Criteria
O’Grady JG,. Early indicators of prognosis in fulminant hepatic
failure. Gastroenterology 1989.

21. Acetaminophen
Non Acetaminophen

22. ALF
• Four predictors of adverse post LTx outcome –
1. BMI ≥30 kg/m2,
2. serum creat >2.0 mg/dl,
3. recipient age >50 years, and
4. requirement for life support.
The relative risk of post OLT mortality increased by
approx. 150% for each additional point.
Barshes et al. Risk stratification of adult patients undergoing orthotopic liver
transplantation for fulminant hepatic failure. Transplantation 2006

23. • low-risk patients (5-year
survival, 81%)
•high-risk patients (5-year
survival, 42%)

24. ALF
European Transplant Registry (ELTR) identified risk
factors for death or graft loss in ALF –
• male recipient gender,
• recipient age >50 years,
• incompatible ABO transplantation,
• donor age >60 years, and
• reduced size graft
Germani G, et al. Liver transplantation for acute liver failure in Europe: outcomes
over 20 years from the ELTR database. J Hepatol 2012

25. 3 Month mortality 12 Month mortality
Death or graft loss independently a/w
•male recipients (adjusted OR 1.25),
•recipient >50 years (1.26),
•incompatible ABO matching (1.93),
•donors >60 years (1.21), and
•reduced size graft (1.54).

26. ACLF - CANONIC study
28-days mortality 22%, 32% and 76.7%
in patients with ACLF grade 1, 2, and 3,
respectively.
Moreau R, et al. Acute on-chronic liver failure is a distinct syndrome that develops in
patients with acute decompensation of cirrhosis. Gastroenterology 2013

27. ACLF
• Initially diagnostic criteria CLIF - SOFA score.
• Simplified scoring system, CLIF-C OFs was developed.
• CLIF-C OFs and 2 predictors (age and WBC) combined
to develop CLIF-C ACLFs
• CLIF-C ACLFs – specific prediction score
Jalan R, et al. Development and validation of a prognostic score to predict
mortality in patients with acute-on-chronic liver failure. J Hepatol 2014

28. CLIF – C OF score
CLIF- C ACLF range –
0 to 100
The C-index for 28-day, 90-day, 6-month and 1-year mortality :
•CLIF-C ACLFs (0.76, 0.73, 0.72, and 0.71) significantly better
•CLIF-C OFs (0.72 [p <0.001], 0.68 [p <0.001], 0.67 [p <0.001], and
0.66 [p = 0.003]),
•CLIFSOFAs (0.72 [p <0.001], 0.68 [p <0.001], 0.67 [p <0.001], and
0.66 [p = 0.002]).

30. ACLF
• ACLF - dynamic process and deteriorates very fast.
• Between day 3 and 7 - crucial for further Mx.
• Early resolution a/w low to mod 28-day Tx free
mortality (6–18%).
• Early severe (ACLF gr 2 or 3) a/w high 28-day Tx free
mortality (42–92%).
Gustot T, et al. Clinical Course of acute-on-chronic liver failure syndrome and
effects on prognosis. Hepatology 2015

31. When to transplant? The concept of a
“transplantation window”
• Dynamic C/I –
1. Uncontrolled sepsis,
2. Severe ARDS,
3. haemodynamic instability
• Resolution/control or
improvement of OFs
define the
“transplantation window”

32. 28-day transplant-free survival
(d3-7)
no ACLF – 89.6%
ACLF-1 - 78.7%
ACLF-2 – 42.9%
ACLF-3 – 12.8%
These differences maintained at
90 and 180 days.
28- and 180-day probability of
survival (d3 – 7 ACLF 2 or 3):
•95.2% and 80.9% who receives
early LT
•23.3% and 10% not
transplanted.

33. ACLF
One-year survival for patients (n-73) with ACLF – 3 with
LT and nontransplanted controls was 83.6% vs. 7.9%.
Large cohort (n – 19,357) - 1-year survival ranging from
88% (1 OF) to 80% (5/6 OFs) post LTx.
However, to obtain these good results a short decision-making
process (transplantation window) is needed.
Artru F, et al. Liver transplantation in the most severely ill cirrhotic patients: A multicenter study in
acute-on-chronic liver failure grade 3. J Hepatol 2017
Thuluvath PJ. Liver transplantation in patients with multiple organ failures: Feasibility and
outcomes. Journal of Hepatology. 2018.

34. Precipitating Events
•28-day Tx free mortality rate of 48 vs. 51% (similar),
•90-day and 1-year mortality significantly better for hepatic
ACLF (90-day: 59% vs. 68%; one-year: 64% vs. 75%)
Shi Y, et al. Acute-on-chronic liver failure precipitated by hepatic injury is distinct from that
precipitated by extrahepatic insults. Hepatology 2015.

35. Physical Fraility
• Term originates from geriatric medicine.
• Decline in reserve and function
• Compromised ability to cope with everyday or acute
stressors.
• An additional tool to guide futility decision making.

36. Physical Fraility
• Several tests objectively assess physical frailty –
1. Fried frailty index,
2. short physical performance battery,
3. six minute walk test,
4. activity of daily living and
5. frailty index
Lai JC. Defining the threshold for too sick for transplant. Curr Opin Organ Transplant
2016.

37. • Each 1-unit increase in the Fried Frailty score a/w 45% (95%CI)
increase risk of wait-list mortality adjusted for MELD.
Lai JC, Feng S, Frailty predicts waitlist mortality in liver transplant candidates. Am J
Transplant 2014.

38. Fraility/Sarcopenia
• It may not possible to perform such tests.
• Evaluation of surrogate marker of frailty (sarcopenia),
represent an alternative option.
• CSA of psoas muscle - valid measure of sarcopenia.

39. • TPMT/height on CT, predictive of mortality in cirrhotic patients,
independent of the MELD and MELD-Na.
• 15% increase in mortality risk per unit decrease in TPMT/height.
Durand F, et al. Prognostic value of muscle atrophy in cirrhosis using psoas muscle
thickness on computed tomography. J Hepatol 2014

40. 1 year survival - 49.7% in
smallest TPA and 87.0% in
largest TPA Quartile.
3 year survival - 26.4% in
smallest TPA and 77.2% in
largest TPA Quartile.
Englesbe MJ. Sarcopenia and Post-Liver Transplant Mortality. J Am Coll Surg. 2010

41. Age & Comorbidity
• The age of liver transplant recipients has increased
steadily over the last 2 decades.
• There is no universal age limit for transplantation
• Frailty and comorbidities are important to consider.
2019

42. •Most series – Similar outcomes - 1 year after LT,
• but 5-year survival is 10 to 20% lower in patients aged ≥60– 70 years than in
younger recipients.

43. Charlson comorbidity Index
• CCI - independent predictor of survival after LT.
Charlson ME. A new method of classifying prognostic comorbidity in longitudinal
studies: development and validation. J Chron Dis 1987.
Volk ML et al. Modified Charlson Comorbidity Index for Predicting Survival After Liver
Transplantation Liver Transpl 13:1515-1520, 2007. © 2007 AASLD

44. POPH
• Reversibility after LT is unpredictable.
• High perioperative mortality.
• High futility if unresponsive to medical management.
• Single centre study - favourable 1-year outcomes in
patients with POPH who maintained cardiac
function.
2016

45. Cardiovascular Disease
• CVD significantly impact outcomes after LT.
• Pre-existing CVD - leading cause of early mortality
(30 days post LT) followed by infection, graft failure,
haemorrhage and renal failure.
VanWagner LB, et al. High early cardiovascular mortality after liver transplantation.
Liver Transpl 2014

46. Cardiac risk score
presence of at least 1 of the following variables:
• severe valvular disease,
• CAD with > 70% stenosis or previous PCI,
• H/O - MI,
• H/O - arrhythmias,
• elevated pre-LT trop I (>0.2 ng/ml),
• new RWMA on 2D Echo.
VanWagner LB, et al. A point-based prediction model for cardiovascular risk in
orthotopic liver transplantation: The CAR-OLT score. Hepatol Baltim Md 2017

48. What management to offer patients
who do not receive a transplant?
• EASL guidelines - withdrawal of ongoing intensive
care support can be suggested who are not
candidates for LT (definitive C/I) and who have 4 or
more OFs after 1 week of adequate intensive
treatment.
European Association for the Study of the Liver . EASL Clinical Practice Guidelines for
the management of patients with decompensated cirrhosis. J Hepatol 2018.

49. Thank You