Patient selection for LT for alcoholic liver disease: - PowerPoint Presentation

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Patient

selection for LT for alcoholic liver disease:

the present situation in Korea and recommendation- Controversial issues in LT for alcoholic liver disease of Korea

PNUYH HBP & LT TEAM

TWO HEARTS

ONE LIVER

ONE LOVE

FOREVER

Pusan National University

Yangsan

Hospital

HBP Surgery and Liver

Transplant Team

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Safe Alcohol Use

-

40 gm/day and 200gm/week for man

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NO CRITERIANO SYSTEM

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EU US REVIEW

KOREA 10 SURVEY

PNUYH EXPERIENCE

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ALD

remains the

2nd most common indication for LT, accounting for app. 40% of all primary LT in Europe and about 25% in US20-45% of patients transplanted with ALD resume some degree of alcohol within 5 years of LT about half have harmful drinking.

Transplantation 2013;95:755

The goal of 6 month rule (6 MoR) - current pre LT requirement at most centers To decrease the risk of recidivism To decrease the risk of graft loss

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≤

6

mo (n=8)7-12 mo (n=33)13-17 mo (n=34)

18-35 mo

(n=43)≥ 36 mo (n=53) P value RR (95% CI) of PD 8.5 (1.4, 51)5.9(1.3, 27)4.3(0.9, 22)1.3(0.2, 9.1)1.0(referent)0.013Risk of PD 38%27%18%5%4%0.001RR (95% CI) of AD 2.8(0.8, 9.7)2.2(0.9, 5.5)1.8(0.7, 4.8)1.3(0.5, 3.6)1.0(referent)0.008Risk of AD50%39%26%19%13%0.022AD, any drinking; CI, confidence interval; PD, problem drinking; RR, risk ratioTandon et al, AJG, 2009Recidivism risk decreases with increasing length of pre LT abstinence Retrospective Canadian study, n=170 LT recipients with ALD, LT between 1991-2007 Compared to abstinent patients transplanted for non-alcoholic liver diseases, the survival rates in patients with recidivism to harmful drinking are similar initially but become worse after 5-10 years (45%-68% vs 75%-86%).J Hepatol 2012; 57: 306Dig Dis Sci 2011; 56: 236

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Declaration

of Istanbul

(2008); Organs should be equitably allocated to recipients without regard to gender, ethnicity, religion, or social or financial status. Do not discriminate against patients based on past behavior unless they have a clear impact on graft

outcome.

The patient survival rates after LT for ALD81%-92%, 78%-86%, and 73%-86% at 1, 3, and 5 years respectively.Transplantation 2013; 95: 755Am J Transplant 2010; 10: 138No difference was seen when comparing the rate of graft loss from all causes after 90 postoperative days between ALD and PBC (hazard ratio 1.4; 95% CI 0.9–2.0). Eu So Or Transpl 2008; 21: 459Patient loss is due to Ca and ASCVD rather than ALDLiver Transpl 2005;11:420

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'Please help me Mum, I don't want to die': Last words of alcoholic, 22, who died after being refused liver transplant

by JULIE MOULT for MAILONLINE

and RYAN KISIEL for THE DAILY MAILDATED: 16:26 GMT, 1 September 2009A young alcoholic denied a liver transplant because he was too ill to prove he could stay. Gary Reinbach, 22, was terrified and pleaded with his mother to do something hours before his death. His last words to her were: 'Please help me Mum, I don't want to die.’ Mr

Reinbach, who lived in Dagenham, Essex, began drinking at the age of 13 following the break-up of his parents' relationship

. Mr Reinbach had the worst case of cirrhosis that doctors had ever seen in a man of his age but they refused to give him a new liver which could have saved his life. National guidelines dictate that to qualify for a donor organ, a potential recipient must prove he has the determination to stop drinking by remaining abstinent for six months. No exceptions for ill patients with high MELDs

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SAH – not responding to medical

Tx

 6 mo survival rate 30%Prospective case control studyFrench 7 centers SAH not responsive to medical Tx No prior episode of alcoholic hepatitis

Having supportive family membersLille score ≥0.45

71% survival at 2 yrs vs 23% Almost 80% of deaths among control Pts occurred within 2 mo after identification of nonresponse to medical therapyEarly Liver Transplantation for Severe Alcoholic HepatitisN Engl J Med 2011;365:1790An obvious ethical question is whether severe alcoholic hepatitis patients who do not respond to treatment should be left to their fate to die or should be considered for LT as suggested by the French consensus group.

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There

is some evidence that shows the duration of abstinence is correlated with less drinking after

LT but there are many other factors that affect recidivism as wellSome factors were found more often than not to be associated with abstinence: social stability, no alcohol problems among first-degree relatives, older age,

no repeated alcohol treatment failures, good compliance with medical care,

no current polydrug abuse, and no co-existing severe mental disorder. 6 MoR was a poor predictor of abstinence despite extensive research and wide usage. Need to develop a standardized multidisciplinary approach including not only 6 MoR but also other various predictors to minimize recidivism

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Although

psychosocial evaluation is mandatory for

all transplant candidates, it is more important in alcoholic cirrhotic. Psychosocial Assessment of Candidacy for Transplantation (PACT) scale is a common tool used at

most centers for evaluating candidates for all types of transplants.JAMA

1989; 261: 2958Psychosocial EvaluationThis scale is used to assess social support, psychological health, life style factors, and patients’ understanding of the transplant process including the follow up process after LT. Pts with intermediate risk for recidivism are recommended to undergo rehab. Tx before being considered for LT.

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A

careful assessment should be made of the effects of alcohol on other organs including the presence of

cardiomyopathy, chronic pancreatitis, Wernicke’s encephalopathy, alcohol-related dementia, peripheral neuropathy, and upper aero-digestive malignancies as these can affect LT candidacy. Clin Liver Dis 2012; 16: 851These issues need to be addressed as they have a negative impact on LT outcome.Therefore, detailed cardiac, neurological, and aero-digestive assessment should be done in alcoholic cirrhotic to assure their LT candidacy.

Medical Evaluation

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Immediate Listing for Liver Transplantation Versus Standard Care for

Child–Pugh Stage B Alcoholic Cirrhosis - A Randomized Trial

Ann Intern Med 2009 150: 153Patients with Child–Pugh stage B alcoholic cirrhosis were randomly assigned in a 1:1 ratio to immediate listing for liver transplantation (60) or standard care (60).

The average Child–Pugh score and MELD score were 8.1

and 14.5, respectively.The incidence of de novo tumors  at least twofold higher in ALD AJT 2010;10:138Upper aero-digestive cancers  10-fold higher risk compared to other indications GE 2009; 137: 2010TP 2003; 35: 1900When we consider LT in ALD MELD score might be greater than 15

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Liver Transplantation

for Alcoholic Liver Disease

KOREAKONOS registryFrom 2000 to 2015Total 12662 patients

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Annual Status of ALD patients in KOREA (2000~2015)

* According to KONOS registry

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Annual Status of ALD patients in KOREA (2000~2015)

* According to KONOS registry

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Etiology of LT patients in KOREA (2000~2015)

42%

17.7%9.3%3.9%

3.7%

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The SURVEY

:

Patients Selection for LT for Alcoholic Liver DiseaseMarch 201610 LT centers in KOREA

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Question 1.

Do you strictly apply the 6-month

rule in your center?

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Question 2.

How

many cases have kept the 6-month rule among ALD patients?

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Question 3.

What

is your diagnostic method for alcohol recidivism?

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Question 4.

How do you make a decision to proceed LT for acute hepatic failure due to alcoholic hepatitis ?

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Question 5.

Do you enforce the prohibition commitment to your patients? If yes, how?

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Question 6.

Do you consult to

psychiatrist about alcoholic abuse?

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Question 7.

Is there any differences of alcohol recidivism between the patients who kept the 6-month rule and the others?

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PNUYH EXPERIENCES

Liver

Transplantation for ALDH OPE

Helping

OutsidePatientsEverywherePusan National University Yangsan Hospital HBP Surgery and Liver Transplant TeamFrom May 2010 to June 2015 Total 229 casesALD 56 cases

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Annual Status of LT for ALD patients in PNUYH (2010. May~2015.June)

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Demographics of the ALD Patients

Variables

Number of patients (%)Gender (male:female)

43(76.8%) : 13(23.2%)

Age51.0±6.50 (range 35-65)MELD24.09±11.23 (range 6-46)Child Classification A4(7.1%) B9(16.1%) C43(76.8%)Etiology Alcoholic only37(66.1%) Combined (HBV, HCV, etc)19(33.9%)Operative Time(min)583.61±187.20 (range 365-1550)LDLT/DDLT25(44.6%) : 31(55.4%)ABO(A/B/O/AB)21/10/12/13

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Overall Survival Rate

Total

patientsNon-alcoholics

ALD patients

1YOS86.8%87.7%83.8%3YOS85.6%87.1%80.3%Survival197/229151/17346/56Non-alcoholicsALD patientsP=0.321 POD 30days Mortality Total patients 6.5% (15/229) Non-alcoholic patients 5.8% (10/173) ALD patients 8.9% (5/56)

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The Cause of Death in ALD patients

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pRBC

Transfusion during Transplantation

P=0.004

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Morbidity of the Recipients

P=0.030

P=0.008P=0.174* All Complication according to

Clavien Dindo

Classification (above IIIA)

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Correlation with

LT type

P=0.051

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Overall Survival Rate LT type

LDLT

DDLT

1

YOS95.8%74.1%3YOS95.8%61.7%Survival24/2522/31LDLTDDLT P=0.009P<0.001

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Overall Survival Rate Alcohol Relapse

Alcoholics Relapse

None

1

YOS100%81.5%3YOS80.0%81.5%Survival6/740/49NoneAlcoholic recidivismP=0.705

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Overall Survival Rate 6-month Rule

Keeping 6-month rule

Not keeping 6-month rule

1

YOS93.2%72.9%3YOS88.6%72.9%Survival19/2627/30Keeping 6-month ruleNot keeping 6-month ruleP=0.056P<0.001

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Correlation between

Alcohol Recidivism and 6-month rule

20.0%3.8%P=0.068

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Correlation between

Alcohol Recidivism

and Multidisciplinary treatment28.6%10.2%

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SUMMARY

Although Korea LT society

doesn’t have any official rule to select patients in ALD for LT, most centers have strictly applied 6 month rule as much as possible. In the context of steadily increased ALD in LT, we definitely need a standardized multidisciplinary approach including not only 6 month rule but also other various predictors s

uch as social stability, no family history, older age, good compliance with alcohol

Tx, no current polydrug abuse, no severe mental disorder to minimize recidivism and to maximize abstinence.

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SUMMARY

SAH not responsive to medical

Tx with no prior episode of alcoholic hepatitis and having supportive family members should be considered for LT. Psychosocial evaluation and support are mandatory especially in ALD.When we consider to perform LT for ALD, MELD score might be ≥ 15 considering high incidence of upper aero-digestive cancer. Based on our primitive experience in ALD PNUYH need more strict selection criteria for ALD patients especially in severely deteriorated cases to enhance organ sparing.

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