AASLD/ILTS Transplant Course · Satisfactory Completion . Learners must complete an evaluation form to receive a certificate of completion. Your chosen sessions must be attended in

AASLD/ILTS Transplant CourseThe Critically Ill Patient and Challenges in Liver Transplantation

Program Chairs:

Sanjiv Saigal, MD Catherine Paugam-Burtz, MD, PhD Roberto Hernandez-Alejandro, MD

Friday, November 8 | 8 am – 3:30 pm

The AASLD EVENTS App is compatible with iPhone, Android, iPad and most tablets.

www.aasldnews.org/mobile-appLEARN MORE

Designed and developed

specifically for The Liver

Meeting® 2019, this mobile

event app delivers educational

sessions and exhibitor content

paired with news, social media

and meeting tools that provide

a best-in-class experience.

EXPLORE • CONNECT • SHARETHE LIVER MEETING® APP

Social Media

Program ExhibitorsMy Schedule

General Info Maps Abstracts

Product Theatre

Course Syllabi

Faculty

Claim CME Daily News

DownloadsAttendeesDonate Now Event Pulse

About This App

SCHEDULING

Exit to Event List

MEETING RESOURCES

E VENTS

Three Easy Ways to ClaimYour CME Credits and MOC Points

The CME/CE/MOC evaluations can be completed in the following ways:

• During the sessions. Use The Liver Meeting® app and evaluate the sessions in real

time. Search “Liver Meeting” in the App Store (for your Apple device) or in Google

Play (for your Android device).

• In your hotel room or at home. Access the evaluation website using your

personal device of choice. A link to the CME, CE and MOC evaluation websites will

be available at aasld.org/livermeeting.

• At the Continuing Education/Certifi cate Stations. Visit this area in Hall A to

access evaluations from any available kiosk.

CME and CE credit will be awarded after you have completed your evaluation. You will

also have the ability to download and/or print a certifi cate for your records.

MOC points are submitted by AASLD to ABIM and ABP on behalf of its learners. Points

are not submitted automatically and will not display immediately on your ABIM or ABP

MOC Profi le upon completion of the MOC evaluation.*

Certifi cates of attendance are also available. They may be downloaded and/or printed

upon completing the overall evaluation for The Liver Meeting®.

Save your badge! Your email address and badge number will

be needed to access The Liver Meeting®/CME evaluation.

*MOC completions are collected on the 15th of each month and submitted to the ABIM and/or ABP by the last day of the month.

The Use of AASLD Scientific Program Content Information presented during the AASLD/ILTS Transplant Course is the property of AASLD and the presenter. Information may not be recorded, photographed, copied, photocopied, transferred to electronic format, reproduced or distributed without the written permission of AASLD and the presenter. Any use of the program content, which includes, but is not limited to, oral presentations, audiovisual materials used by speakers and program handouts without the written consent of AASLD, is prohibited.

Table of Contents 2019 AASLD/ILTS Transplant Course Continuing Education Information ..................................................... 1

Program Agenda ........................................................................................................................................... 3 Session I Presentations: Assessing Frailty and Malnutrition Jennifer C. Lai, MD ........................................................................................................................................ 5 Gender Disparities in Access to LT in the Very Sick Patient Monika Sarkar, MD, MAS ............................................................................................................................ 27 Assessment of Volume Status in the Fluid Overload Critically Ill Patient François Durand, MD .................................................................................................................................. 66 Neurocognitive Assessment of the Sick Intubated Patient Ram M. Subramanian, MD, FAASLD ........................................................................................................... 77 Session II Presentations: Hepatopulmonary Syndrome and Portopulmonary Syndrome James Findlay, MB ChB, BSc ........................................................................................................................ 90 Coronary Artery Disease Before Transplantation (Stent or Not Stent) Lisa Van Wagner, MD, MSc....................................................................................................................... 114 Window Opportunities in the Very Sick Patients with Sepsis in the ICU? Catherine Paugam-Burtz, MD, PhD ........................................................................................................... 145 Selection Issues in Critical ACLF Patient (the optimal timing for LT, diagnostic criteria for ACLF) Constantine Karvellas, MD, SM, FRCPC ..................................................................................................... 146 Early Liver Transplantation for Severe Alcoholic Hepatitis Debate Disscusants: Ramon Bataller, MD, PhD and Carmen Vinaixa, MD ........................................................... 180 Session III Presentations: Morbid Obesity in the Transplant Recipient Julie Heimbach, MD, FAASLD .................................................................................................................... 218 The Need of LDLT in the US, Initiating a Program Roberto Hernandez-Alejandro, MD ......................................................................................................... 249 Altruistic LDLT, is it Feasible? Elizabeth Pomfret, MD, PhD ..................................................................................................................... 276

The Use of AASLD Scientific Program Content Information presented during the AASLD/ILTS Transplant Course is the property of AASLD and the presenter. Information may not be recorded, photographed, copied, photocopied, transferred to electronic format, reproduced or distributed without the written permission of AASLD and the presenter. Any use of the program content, which includes, but is not limited to, oral presentations, audiovisual materials used by speakers and program handouts without the written consent of AASLD, is prohibited.

Challenges in Pediatric Liver Transplantation Yuri Genyk, MD ......................................................................................................................................... 311 Debate on Simultaneous Kidney/Liver Transplantation UNOS Policy Disscusants: Vatche Agopian, MD and Mitra Nadim, MD ........................................................................ 347 Faculty, Planner and AASLD Staff Disclosures .......................................................................................... 381

2019 AASLD/ILTS Transplant Course The Critically Ill Patient and Challenges in Liver Transplantation

Friday, November 8, 2019 8 am – 3:30 pm

Program Chairs: Sanjiv Saigal; Catherine Paugam-Burtz and Roberto Hernandez-Alejandro

Session Description/Needs Statement This course will review the perioperative challenges faced in very sick liver transplant candidates, and is useful for intensivists, hepatologists, anesthesiologists and surgeons. Liver transplantation outcomes in sick patients significantly depend on perioperative management. Faculty will address the special challenges faced in liver transplantation, including those of living donor organs.

Learning Objectives Upon completion of this activity, participants will be able to:

• Review the various perioperative challenges faced in the management of very sick livertransplant candidates

• Describe the special challenges faced in liver transplantation such as morbid obesity,simultaneous liver & kidney transplantation and living donor liver transplantation

• Appraise recent advances & innovations in the field of liver transplantation

CONTINUING MEDICAL EDUCATION (CME) Accreditation Statement The American Association for the Study of Liver Diseases (AASLD) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Credit Designation Statement AASLD designates this live activity for a maximum of 6.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

The CME/CE* evaluations are available online and can be completed in the following ways: • During the session:

Download The Liver Meeting® app and evaluate the sessions in real time – refer to the CME iconto access the evaluation.

• In your hotel room or at home:Access the evaluation website using your personal device of choice. Go directly to the CMEevaluation and/or CE* evaluation.

• At any Continuing Education/Certificate Stations:Visit the Continuing Education/Certificate Stations in Hall A to access the evaluation from anyavailable kiosk.

Certificates of Attendance Certificates of Attendance are available to attendees completing The Liver Meeting® evaluation and may be printed on-site in Tech Connect or after the meeting at aasld.org/livermeeting by March 15, 2020.

1

CONTINUING EDUCATION (CE) STATEMENT Satisfactory Completion Learners must complete an evaluation form to receive a certificate of completion. Your chosen sessions must be attended in their entirety. Partial credit of individual sessions is not available. If you are seeking continuing education credit for a specialty not listed below, it is your responsibility to contact your licensing/certification board to determine course eligibility for your licensing/certification requirement.

Nurses In support of improving patient care, this activity has been planned and implemented by Amedco LLC and the American Association for the Study of Liver Diseases. Amedco LLC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Credit Designation Statement— Amedco LLC designates this live activity for a maximum of 6.0 contact hours for nurses. Learners should claim only the credit commensurate with the extent of their participation in the activity.

Nurse Pharmacology Credits Please note onsite agenda for identification of sessions eligible for pharmacotherapeutic hours and self-submit those to your board. Keep the agenda as a reference in case they have questions.

DEADLINE: Be sure to complete the CME and/or CE evaluation for credit at aasld.org/livermeeting before the following dates:

• CME evaluation – March 15, 2020• CE* evaluation – December 31, 2019

2

2019 AASLD/ILTS Transplant Course Program Agenda

Session I: Perioperative Challenges in the Very Sick Liver Transplant Candidate – Part I Moderators: Catherine Paugam-Burtz and Kymberly Watt

8:00 – 8:05 AM Welcome and Introductions

8:05 – 8:25 AM Assessing Frailty and Malnutrition Jennifer C. Lai, MD

8:25 – 8:45 AM Gender Disparities in Access to LT in the Very Sick Patient Monika Sarkar, MD, MAS

8:45 – 9:05 AM Assessment of Volume Status in the Fluid Overload Critically Ill Patient François Durand, MD

9:05 – 9:25 AM Neurocognitive Assessment of the Sick Intubated Patient Ram M. Subramanian, MD, FAASLD

9:25 – 9:40 AM Panel Discussion

9:40 – 9:55 AM Break

Session II: Perioperative Challenges in the Very Sick Liver Transplant Candidate – Part II Moderators: Catherine Paugam-Burtz and Sanjiv Saigal

9:55 – 10:15 AM Hepatopulmonary Syndrome and Portopulmonary Syndrome James Findlay, MB ChB, BSc

10:15 – 10:35 AM Coronary Artery Disease Before Transplantation (Stent or Not Stent) Lisa Van Wagner, MD, MSc

10:35 – 10:55 AM Window Opportunities in the Very Sick Patients with Sepsis in the ICU? Catherine Paugam-Burtz, MD, PhD

10:55 – 11:15 AM Selection Issues in Critical ACLF Patient (the Optimal Timing for LT, Diagnostic Criteria for ACLF) Constantine Karvellas, MD, SM, FRCPC

3

11:15 – 11:45 AM Debate: LT for Severe Acute Alcoholic Hepatitis Pro: Carmen Vinaixa, MD Cons: Ramón Bataller, MD, PhD 11:45 AM – Noon Panel Discussion Noon – 1:20 PM Intermission Session III: Special Challenges in Liver Transplantation Moderators: Sanjiv Saigal and Roberto Hernandez-Alejandro 1:20 – 1:40 PM Morbid Obesity in the Transplant Recipient Julie Heimbach, MD, FAASLD 1:40 – 2:00 PM The Need of LDLT in the US, Initiating a Program Roberto Hernandez-Alejandro, MD 2:00 – 2:20 PM Altruistic LDLT, is it Feasible? Elizabeth Pomfret, MD, PhD 2:20 – 2:40 PM Challenges in Pediatric LT Yuri Genyk, MD 2:40 – 3:10 PM Debate on Simultaneous Kidney/Liver Transplantation

UNOS Policy Pro: Vatche Agopian, MD Con: Mitra Nadim, MD 3:10 – 3:25 PM Panel Discussion

3:25 – 3:30 PM Closing Remarks

4

Morbid Obesity in the Transplant Recipient

Julie Heimbach Professor of Surgery and Chair Division of Transplantation Surgery Mayo Clinic, Rochester MN The worldwide obesity epidemic has significantly impacted the liver transplant landscape. Obesity can be the cause of liver disease due to metabolic syndrome resulting in NAFLD and NASH. Outcomes after liver transplant for NASH and NASH-related HCC are comparable to other indications. However, this requires a careful selection of candidates with special attention to their cardiovascular health, physical debility, sarcopenia, and glycemic control. To ensure positive long-term outcomes, it requires an enhanced multi-disciplinary team that includes specialized dieticians, psychologists, social workers and for selected patients, a bariatric team. It is imperative to carefully manage their nutrition, medication intake, and ambulatory status during the peri-operative phase, and follow-up on their metabolic targets post-operatively as the risk of recurrent obesity and NAFLD is high. Weight loss strategies can be non-invasive or surgical, and may be integrated into the course of treatment before, during, or after liver transplant, with the major limiting factor being the patient’s severity of liver disease. Combining liver transplantation and bariatric surgery at the same setting is an option, and a sleeve gastrectomy appears to be the bariatric procedure of choice in this setting.

218

Slides are the property of the author and AASLD. Permission is required from both AASLD and the author for reuse.

Morbid Obesity in the Transplant Recipient

Julie Heimbach Professor of Surgery and Chair

Division of Transplantation SurgeryMayo Clinic, Rochester MN

219


• Outline current scope of the obesity epidemic

• Implications of obesity pre and post LT

• Discuss the role of bariatric surgery

Objectives

220


- World wide, obesity has doubled since 1980- Currently, 600 million obese adults in the world

221


The systemic impact of obesity

5222


Impact of obesity on incidence of NASH• 1/3 US population is obese

• 2/3 of obese people have steatosis (108 million US).

• Of these, 2/3 remain with bland steatosis, 1/3 progress to steatohepatitis (30 million)

• 5-15% progress to cirrhosis (3 million US)

6223


NASH as an indication for listing for liver transplantation in US

7224


Impact of obesity on pre-transplant patient selection

Ekstadt et al Hepatology 2006:4;865-73. Vanwagner et al Hepatology. 2012 Nov;56(5):1741-50Choudary et al Clin Transplant 2015: 29: 211–215.

• Most common cause of death for patients with NAFLD is a cardiovascular event.

• Patients who undergo LT for NASH may be at an increased risk for perioperative/post-op cardiac events

• Sarcopenia is associated with worse outcomes, including patients with sarcopenic obesity

225

Slides are the property of the author and AASLD. Permission is required from both AASLD and the author for reuse.Liver Transplantation 2009

Impact of obesity on outcome:

• SRTR data 1987-2007• 68,172 BMI 18.5-40, 1827

<18.5, and 1,447>40.• Outcome worse high and low

BMI patients (similar to previous report Nair et al 2002)

• No correction for ascites, small number of patients in each of the “extreme” groups

Dick, Liver Transpl. 2009:15;968-77.

226


• SRTR 2004-2011

• N=38,194• Compared <18.5, 18.5-45, >45.

• BMI<18.5 associated worse survival

• No difference in outcomes for obese patients

Orci Transpnt Int. 2012: 26;170-6.

female

male

Impact of obesity on outcome

227


Impact of obesity on long term outcome

• Multi-center Australian LT cohort N=617 2002-2009

• Obese plus Diabetes associated with worse outcomes at 5 years post LT.

• Obese non-DM and non-obese DM were both similar to non-obese, non-DM.

Watt. AJT 2010

Adams et al:Journal of Gastroenterology and Hepatology 31 (2016) 1016–1024

228


Impact of weight loss on liver fibrosis:• 45 patients, followed for mean of 4.6

years with serial biopsies every 5 years

• 12 patients with bariatric surgery, 6 more who lost weight with medical management

• On multivariate analysis, only weight loss of >10 % TBW predicted fibrosis regression, OR 8.14

Glass et al. ( Dig Dis 2015 60:1024–1030)

229

*Sjostrom et al NEJM 2007;357:741-752

Bariatric surgery provides effective long-term weight loss

230

12 year outcomes post Roux-Y Gastric bypass:

• 95% reduction in new-onset DM at 12 years

• 51% resolution of DM type II at 12 years

• Effective long-term weight loss

Adams et al NEJM 2017: 377; 1143-55.

231


Bariatric surgery proceduresRestrictive• Lap band: reversible, low rate of

serious complications. Less effective weight loss, and >50% failure rate at 10 years. ? Access to distal varices

• Gastric sleeve: slower weight loss, low rate of complications, appears durable (early). Not reversible. Preserves access to biliary tree and varices.

Restrictive +Malabsorptive• Roux-en-Y Gastric bypass: gold

standard. Effective, long-term weight loss. Serious complication rate 0.5-2%. No access to distal varices. ? Rapid weight loss

• Duodenal switch: rarely used, reserved for very severe obesity. Not appropriate for patients with liver disease.

15232


Bariatric Surgery in patients with cirrhosis

• 5 studies (13-23 patients)• Lap sleeve gastrectomy or RYGB• Longer OR time and higher

complications • Conclude: bariatric surgery safe,

effective in selected patients with compensated cirrhosis (child’s A.)

Lin et al Obes Relat Dis. 2013;9(5):653–8. Woodford et al Obesity Surg (2015) 1623-9. Shimizu et al Obesity Rel Dis (2013)9;1–6. Rebibo et al Obesity Rel Dis (2014)405-10. Pestana et al Mayo Clin. Proc. (2015)209-15

233


• UCSF N= 32

• MELD=12 (11-13)

• BMI=45

• No deaths

• 1 leak

• 21 listed and 14 transplanted

Sharpton Liver Trans 2019

234


Bariatric surgery in cirrhosis • Nationwide Inpatient Sample (NIS) between 1998 and 2007

• Patients identified as having bariatric surgery and decompensated cirrhosis (n=62), compensated (n=3888) or or no cirrhosis (n=670,950).

• Diagnosis code of ascites or varices required to be classified as decompensated.

• In-hospital mortality 16.3 % vs 0.9% and 0.3%,( P <.0002).

• LOS higher in cirrhosis: 6.7 and 4.4 d vs 3.2 d, respectively; P<.0001.

18235


Post LT bariatric surgery• Lin et al: Lap gastric sleeve post

LT n=9 patients• Mean time from transplant 5.9

years, age=56, BMI=41, OR time 165 minutes (lysis of adhesions), hospital stay 5.6 days

• Mean f/u 6 months• 3 patients required re-op in first

30 days

19236

Post LT bariatric surgery• open RYGB post LT n=7 patients• Mean time from transplant 2.6 years, age=56, BMI=44• Mean f/u 5 years• 2 patients died in first 1 year, and 1 reversal

Al-Nowaliti et al (LT 2013;19(12):1324-9): 237


Post LT bariatric surgery• N=6 post LT SG. (3 open, 3 lap).

Performed at average of 43 months post LT.

• Mean follow up 37 months• Median LOS =9 days, 1 leak with

subsequent prolonged stay/multiple reoperations/death. One complication > 30 days (infected mesh requiring re-op).

• Mean BMI 28 post procedure.

21

2017 Aug 3. 7:

238


Perioperative bariatric surgery: MCR Approach

• Enroll all pre-transplant patients with BMI>35 in an obesity management protocol: 4 step approach, goal is BMI<35

• Calorie restricted diet • Food record • Weigh and record.• Activity: determine restrictions, pedometer, etc.

239


• Option for selected patients who have not attained goal weight and have high MELD

• Gastric sleeve resection combined with liver transplant

• No malabsorption, slower weight loss, technically easier

Heimbach et al AJT 2013240


24241


Long-term outcomes of patients undergoing simultaneous Liver Transplantation and Sleeve Gastrectomy

• N=29 LT+SG, with 17 >3 years of follow-up, 36 LT alone

• 29.4% of patients in LT cohort maintained >10% loss in TBW, while 100% of the LT+SG patients did (p<0.001)

• %TBWL= LT cohort 3.9±13.3% vs. LT+SG cohort 34.8±17.3%; p<0.001)

Zamora-Valdez et al, Hepatology Feb 2018

242



Zamora-Valdez et al, Hepatology Feb 2018

243



Less DM, less hypertension, lower triglyceridesZamora-Valdez et al, Hepatology Feb 2018

244


Treatment:Compensated cirrhosis

Goal attain >10% body weight loss to improve liver fibrosis, metabolic

complications

Non-invasive weight loss

Consider lap sleeve gastrectomy (or LRYGB)

Decompensated cirrhosis

Transplant candidate?

Non-invasive attempt at weight loss (selected)

Sleeve gastrectomy (during or after LT)

245


Summary for liver transplant:• Post LT outcomes for selected obese patients appear acceptable• Complications may be higher• Long term outcomes post LT impacted by obesity

• Lifestyle modification• Pre-transplant obesity surgery: highly selected patients• Post-transplant obesity surgery: favor Lap sleeve• Combined approach may be an option for selected patients who have

not attained goal weight

246


Key Take Home Points:

• Post LT outcomes for selected obese patients appear acceptable

• Complications may be higher

• Long term outcomes post LT impacted by obesity• Lifestyle modification• Pre-transplant obesity surgery: highly selected patients• Post-transplant obesity surgery: favor Lap sleeve• Combined approach may be an option for selected patients who have not

attained goal weight

247


Questions? [email protected]

248

The Need of LDLT in the US, Initiating a Program Roberto Hernandez-Alejandro Professor of Surgery University of Rochester Medical Center Living liver donation has waxed and waned in popularity in the United States since its debut in 1989. In an era where the waitlist continues to outpace available deceased donor organs and thousands die waiting yearly, expanding and LDLT is one viable option to increase transplantation. Live donor hepatectomy has proven to be a safe procedure that offers recipients equivalent- or better graft survival than deceased donation; but starting a program is not a task that should be taken lightly. The proper environment, resources, and team (technically experienced surgeons, independent donor advocate, supportive administration, etc.) are foundational. The potential impact of a well-formed program, such as reducing waitlist mortality and expanding your recipient population are boundless.

249

The Need of LDLT in the US, Initiating a Program

Roberto Hernandez- Alejandro, MD, FACSProfessor of Surgery

Chief, Division of Abdominal Transplant Hepatobiliary Surgery

250

In the United States• 38,050 liver Tx in the last 5 years (7,610/yr)

• 89% DBD

• 6% DCD

• 5% LDLT

GODT 2018 data

0

200

400

600

800

1000

1200

1400

France UK Canada Brazil Japan US SouthKorea

Turkey India

International Comparison of LDLT/yr

251

The Critical Need of Organ Donation

010,00020,00030,00040,00050,00060,00070,00080,00090,000

100,000110,000120,000130,000

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

2013

2014

2015

2016

2017

2018

Transplants Deceased DonorsSize of Waiting Lists Living Donors

OPTN Data updated 9/19/19 (all donors, all organs, all ages)

252

DCD/ECD Increase over the Past Decade in the US

OPTN Data updated 9/30/19

0

200

400

600

800

1000

1200

1400

1600

2009 2010 2011 2012 2013 2014 2015 2016 2017 2018

Older and DCD Liver Donors 2009-2018

65+ DCD

253

US Living Donor Liver Transplant Numbers

254

Living Donor Hepatectomy-Donor Mortality

• 26 “perioperative” (related or possibly related)

• 7 late (> 1 year)

• Poorly documented: probably + at least 4

• 18 RL, 7 LL or LLL, others unknown

• Estimated 14,000 LD hepatectomies

• Mortality = ~0.2%

• USA: 5 / 4,534 = 0.1%

• Since 2008 - At least 3 more

• USA – 2 (2010)

• India – 1 (2010)

33 Deaths after Living Liver DonationRinge and Strong, Transpl 2008: 85:790-2

255

Requiem for a Champion?

Clavien PA, Dutkowski P, Trotter JF. Requiem for a champion? Living donor liver transplantation. J Hepatol. 2009 Oct;51(4):635-7.

256

Donor Risk

National Data

• Overall complications 30%• Major complications 10%

6826 LDLT(Jan 2019)

6 donor deaths(0.10%)

3 donors received a LTX

257

Regional Variation

• > 4-fold differential in DBD liver availability according to UNOS region

Jay CL, et al. J Hepatol. 2011 Oct;55(4):808-13.

258

Does Every Center Need a LDLT Program

Median MELD at Transplant

Transplant Rate

Waitlist Mortality Rate

Regional Organ Acceptance Rate Ratio0.8

0.9

1.0

1.1

1.2

1.5

259

Who Should Have a LDLT program?

1) A team dedicated and a similar vision and support for LDLT

• Hepatologist

• LDLT Coordinators

• Outreach/marketing

2) Surgeons with skills and knowledge

• LT and HPB

• Experience in LDLT (overseas)

• At least 2

3) Be prepare for a bad outcome or a fatality

• Need to have a disaster plan

260

Outcomes: Living vs. Deceased Donor Graft Survivalby Era and Age (UNOS Data)Adult

Pediatric

Gruessner. Transplantation proceedings. Vol. 50. No. 10. Elsevier, 2018.

261

LDLT in Rochester - PhilosophyLDLT may be the best choice for most recipients. This procedure provides a healthy

organ

1. Maximizing recipient benefits

2. Offering the opportunity to help a “loved one”

3. Increasing the number of DD organs for others

Our focus is on

1. Donor safety

2. Ensuring an autonomous, well-informed donor choice

3. Advancing knowledge.

262

Liver Transplant Volume URMC since LDLT Restart

05

1015202530354045

Living DonorsDCD DonorsBrain Dead Donors

263

Liver Catchment Area- New Allocation

264

From Liver Resection to Live Donor Liver Tx

265

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwiiwbCPgtTdAhVkS98KHTysCyMQjRx6BAgBEAU&url=https://www.mayoclinic.org/tests-procedures/liver-transplant/about/pac-20384842&psig=AOvVaw2qVo741KcwmaglQoqrkqCN&ust=1537891386935325

Living Liver Donation Safety

• Full disclosure of donor and recipient results.

• HPB “field strength”

• A well-resourced, cohesive team focused on patient safety:• Checklists• Weekly planning mtgs• Continuous quality review• Ethics support• Disaster plan

• A shared commitment to quality improvement & generating new knowledge.

266

267

268

269

Tumor Board Consensus

• Start Systemic Chemotherapy

• FOLFOX 12 treatments

• Bevacizumab

• Re-assess in 6 months

270

#chemo treatment and CEA

607

227

28 8.7 3.4 2.1 3.40

100

200

300

400

500

600

700

Baseline Cycle 2 Cycle 4 Cycle 6 Cycle 8 Cycle 10 Cycle 12

CEA and Chemo Treatment

CEA and Chemo Treatment

271

Is he a candidate for Liver TX?

• Unresectable

• > 1 year responding to chemo

• K Ras Wild type

• CEA below 80

• Max tumor diameter< 5.5 cm

• ECOG 0

• Potential LD

272

Road to transplant

Primary to be removed

Review Pathology of primary

No progression for 3 months

Complete LD work up

Transplant

273

Outcomes SECA-II: No evidence of disease

5y = 67,0%

274

THANK YOU !!!

275


Altruistic Living Donor Liver Transplantation: Is It Feasible?

Elizabeth A. Pomfret, MD, PhD, FACSProfessor of Surgery and Igal Kam MD Endowed Chair of Transplant Surgery

Chief of Transplantation, University of Colorado Anschutz Medical Campus

276


Living Donor Liver Transplantation: AdvantagesShorter waiting time for the recipients with lower wait-list mortality and similar posttransplant survival

Berg et. al. (Hepatol 2011; 54:1313-21)reported a 56% lower risk of death for patients who choose LDLT vs. those waiting for a DDLT.

Despite this only about 5% of liver transplants in the US are LDLT

277


Why is live donation necessary at all and is it different depending on donor relationship to the recipient?

Even in countries with adequate access to DDLT, live liver donation is appropriate due to organ shortages

Donor safety is of paramount importance in living donor liver transplantation and yet living donor complications and deaths occur even in the most experienced hands (0.1–0.5% mortality, 10–38% morbidity)

278


Right Lobe

Risk of Death 1 in 200

Risk of Complication 30-40%

Left Lobe

Risk of Death 1 in 1000

Risk of Complication 10%

Barr ML et al. Transplantation. 2006Cheah YL and Pomfret EA. Liver Transpl. 2013.

1 in 500

Living Liver Donor Morbidity & Mortality

Program Experience

Selection of Donors

Extent of the Donor Hepatectomy

279


A Report of the Vancouver Forum on the Care of the Live Organ Donor: Lung, Liver, Pancreas, Intestine Data and Medical Guidelines

Barr ML, Belghiti J, Villamil FG, Pomfret EA, Sutherland DS, Gruessner RW, LangnasAN, Delmonico FL. Transplantation. 2006; 81(10): 1373-85

280


Donor Safety is of Paramount Importance

The “Vancouver Forum” held in 2006 established practice principles for LDLT:

Live liver donation should only be performed if the risk to the donor is justified by the expectation of an acceptable outcome in the recipient.

Indications for LDLT should be the same as those established for DDLT with the exception of institutionally-approved protocol studies that consider LDLT preferential to DDLT.

LDLT should offer an overall advantage to the recipient when compared to waiting for an acceptable DD organ to become available for transplantation. The decision to proceed with a LDLT should be made after a careful analysis of the recipient risk to benefit ratio as it relates to severity of liver failure, quality of life and expected wait list time for a deceased donor.

Barr ML et al., Transplantation 2006;81:1373–85. 281


What is Double Equipoise?

As long as there is a disparity between supply and demand of DD livers, organ allocation and the system of distribution must be based on the ethical principles of utility, justice and equity.

Utility represents the beneficial outcome of the transplant (i.e. patients likely to have the best survival). Justice implies that all candidates have equal access to transplant.Equity often interchanged with justice, ensures that the organ allocation policy is applied equally and that similar recipients have equal priority.

In living donation, the ethical principles of justice and equity used for deceased donation do not applysince the recipient is not competing with other listed candidates for organs. In fact, live donor liver transplant recipients may benefit all candidates awaiting deceased donor liver transplantation by eliminating themselves from the waiting list.

282


Miller CM. Transplantation Rev. 2008.Barr ML et al. Transplantation. 2006.

Pruett el at. Transplantation. 2006.

Beneficence: “Do good”Expected Recipient Outcome

Non-Maleficence: “Do no harm”Donor Safety

Utility: “Promote Net Good”Need

Autonomy

Principals Unique to DDLT:Justice - all candidates have equal access to transplant

Equity - applying organ allocation equally

283


Concept of Double Equipoise

Describes the balance between the recipient’s survival benefit with or without a live donor transplant and the probability of donor mortality risk.

Risk/benefit analyses for LDLT are not confined to those of the individual donor and recipient, but include balancing the donor risk against the recipient benefit.

The concept of double equipoise suggests that there clearly exists an area of excessive donor risk and unacceptably low recipient benefit.

Ethically unacceptable for LD to undergo an operation that had a mortality risk > 0.5%-1%, nor would it be acceptable for the donor to undertake any risk if the recipient benefit were very low.

284


Concept of Double Equipoise

Conversely, there are situations of donor/recipient balance that appear to be ethically acceptable. Adult donor providing a liver segment for the pediatric recipient.

Here the donor risk is well defined and small, and recipient benefit is almost always a highly successful and durable transplant.

The two extremes appear easily definable and defensible, the zone of “ethical uncertainty” is the most complex area.

What are the minimal benefits to recipients that warrant the use of a live donor and how is use of a live donor for extended indications and marginal recipient benefit justified?

285


The concept of double equipoise describes the balance between the recipient’s survival benefit with or without a LDLT and the probability of donor mortality risk

Pomfret et al. 2011 Liver Transplant. Suppl 2: S128-132286


AltruismThe word was coined by the French philosopher Auguste Comte from

the Latin word alteri, meaning “other people” or “somebody else”

“The belief in or practice of disinterested and selfless concern for the well-being of others.”

“Principle and moral practice of concern for the happiness of other human beings, resulting in a quality of life both material and spiritual.”

Synonyms: selflessness, benevolence, humanitarianism, kindness, charity, social conscience, philanthropy

287


Is There a Hierarchy of Altruism? • Perhaps the most unique form of altruism is an act undertaken which

has risk to the benefactor in an effort to help an unknown or anonymous beneficiary.

Zwick and Fletcher’s Levels of Altruism

Description Type of Living Organ Donor and Example

Human Species Altruism Universal ethics calls for other species to be regarded as oneself

Anonymous non-directed donation

Group Altruism Solidarity with members of one’s community or ethnic group. The key is the extension of self to encompass others

Anonymous non-related directed donationEx: donation to an anonymous church member

Interaction Based Altruism

Altruism towards agents in direct interaction with the individual. Information available to be assured or reciprocal altruism. The Golden Rule: “Do onto others as you would want them to do onto you”

Non-related directed donation Ex: donation to a friend

Kin Altruism This bond is not free of self-interest Related directed donation Ex: donation from a parent to child

Self Interest The foundation of action for others is action for oneself To seek medical attentionEx: to be listed for transplant

Adapted from Zwick and Fletcher’s Levels of Altruism 288


289


29 Consecutive anonymous potential liver donors12 accepted (6 male and 6 female) and 17 rejected4 directed towards recipients who undertook media appeal5 LLS and 7 RLDonor morbidity: 40% (1 Clavien 3: PTX)All doing wellNone regret donation

All donors were strongly motivated by a desire and sense of responsibility to help others.

290


Assessment: used standard live liver donor assessment process, augmented with the following additional acceptance criteria: a logical rationale for donation, a history of social altruism, strong social supports and a willingness to maintain the confidentiality of patient information

291


292


293


294


295


296


Probability trade-off technique

297


Donors inclination to undergo hepatectomy in relation to:

298


299


Conclusions:1. Today: mortality is between 0.1%-0.5% and recipient 5-year survival exceeds 70%2. Participants in this study were willing to accept 70% risk for morbidity and 30% risk for mortality and recipient life gained of 6 months3. Donors are willing to accept a greater level of risk then the clinicians

300


Living donation and cosmetic surgery: a double standard in medical ethics?

Testa, G., et al. J Clin Ethics. 2012; 23(2):110

•Commitment of the transplant MD to protect the physical and psychological health of the donor

•Appropriate that strict regulations to govern an individual’s decision to donate have been developed

•One argument: adherence to these regulations creates a doctor-patient relationship that is rooted in paternalism

•This is in direct contrast to doctor-patient relationship rooted in patient’s autonomy(e.g. cosmetic surgery)

301


Living donation and cosmetic surgery: a double standard in medical ethics?

Testa, G., et al. J Clin Ethics. 2012; 23(2):110

•Argue that both operative interventions should be guided by the same ethical principle: a respect for the patient’s autonomy

•Conclude that if living organ donation valued donor autonomy as much as cosmetic surgery does, we might see a wider acceptance and more living donation

302


303


Case: R.L.• Donor: In 2017, a 28 year old female

approached us asking to donate to someone in need. She had no recipient in mind. Would donate to an adult or child.

• She was a prior non-directed kidney donor

• Her mother was a prior kidney donor• She was raised in a religious household• She came for a 2 day evaluation including

psychological evaluation• 5 ft 9 in; 70 kg• LLSeg 249g (17.8% TLV)

• Recipient: a child with biliary atresia

LLS

RL

304


Case of M.R.41 year old former Navy SEAL learns of a young mother of 3 in need of a liver transplant. He would be suitable as a left lobe donor.

305


36 year old mother of 3 (ages 12, 10, 7) learned of a 58 year old woman in her church with PSC in need of a liver transplant. The donor feels a moral obligation to help if she can and hopes that someone would do the same for her. She would require a right hepatectomy to be sufficient for the donor

306


A selfless behavior undertaken to benefit someone other than oneself Some have questioned if altruism truly exist

https://www.donoralliance.org/newsroom/donation-essentials/colorado-earns-top-spot-in-the-nation-for-highest-donor-designation-rate-wyoming-sixth-in-the-nation/

Altruism in Colorado

307

https://www.donoralliance.org/newsroom/donation-essentials/colorado-earns-top-spot-in-the-nation-for-highest-donor-designation-rate-wyoming-sixth-in-the-nation/


The Colorado ExperienceAltruistic Non-Directed Liver Donors

Donor Characteristics n=13

Median Age at Donation 39 (22-53)

Female 77% (10/13)

Median BMI 25 (21-32)

History of altruism * 100%

Prior kidney donation 62% (8/3)

0

1

2

3

4

5

6

7

8

9

2017 2018 2019

Altruistic Live Liver Donor Surgeries

LLS LL RL

*employment in a field characterized by sacrifice: military, peacecorp, teacher; history of volunteer work or blood donation

Donor Complications n=13

Readmission 23% (3/13)

wound infection 8% (1/13)

duodenal ulcer due to excess NSAID use 8% (1/13)

pain requiring nerve block 8% (1/13)

Center data 9/2019308


Donor Outcomes and Motivations All donors are back to their normal level of activity All of our donors say if given the chance they would donate again

”Because I value life; there are people in need“ "I just wanted to help someone and I felt like I was healthy and able to do this“ ”No one deserves to die“ ”After having donated the kidney I had participated in a fundraiser and we

stayed and listened to the testimonials and I decided I wanted to pursue it in the future" ”We're a community and have to take care of each other"

Center data 9/2019309


Conclusions1. Altruistic donation (directed and non-directed) is ethically appropriate and is an example of pushing the limits in living donors.

2. Unlike DDLT, LDLT is governed by utility concerns that we describe as “double equipoise,” and NOT by equity and justice considerations.

3. Altruistic non-directed donors increase the total organ pool and benefit all potential recipients on the list.

4. Altruistic non-directed donors are motivated by their values and are very satisfied with their experience (essentially all would do it again).

310


Challenges in Pediatric Liver Transplantation

Yuri Genyk, MD Program Director

Children’s Hospital Los Angeles

University of Southern California

311


Barriers to ideal outcomes after pediatric liver transplantationNg, VL, et.al Pediatr Transplant 2019

312


Challenge:To Eliminate Pediatric Liver Waitlist Mortality

Each year, approximately 60 children, representing 12% of waitlist candidates, die awaiting liver transplantation

• Is PELD accurate in predicting pre-transplant mortality

• Is there a shortage of liver donors?/Liver allocation in pediatric recipients

• Transplant options - CAD vs. SLT vs. LDLT

313


Selection of Pediatric Candidates Under the PELD System

McDiarmid, SV et.al. Liver Transplant 2004

314


Predicted probability of waiting survival at 3 months by severity scores

315


Reasons for removal from the liver waiting list before and after implementation of MELD/PELD

316


Death adjusted per 1,000 patient years on theliver waiting list before and after implementation ofMELD/PELD

317


Conclusions

• The PELD score accurately predicts the 3 month probability of waiting list death for children with chronic liver disease

• Comparing pre and post PELD and MELD implementation, the percent of children receiving deceased donor livers increased and the percent of children dying on the list decreased after PELD/MELD implementation.

• Excluding children transplanted at status 1, the largest percentage of children are transplanted at a PELD score<10.

• Before MELD/PELD 48% of all children receiving deceased donor organs were transplanted at status 1, compared to 41% in the PELD/MELD era

318


Impact of the Pediatric End‐Stage Liver Disease (PELD) growth failure thresholds on mortality among pediatric liver transplant candidatesSwenson, SM et.al. AJT 2019

319


(PELD calculator simulation): Impact of PELD's growth failure thresholds on PELD score

320


Prevalence of growth failure, by age and growth failure definition

321


Mortality on the pediatric liver transplant waitlist within 6 months of listing

322


Conclusions

• Current methods for determining growth failure in PELD disadvantage candidates arbitrarily and increase their waitlist mortality risk.

• PELD should be revised to correct this disparity.

323


Accuracy of the Pediatric End-stage Liver Disease Scorein Estimating Pretransplant Mortality Among Pediatric Liver Transplant CandidatesChang, CCH, et.al. JAMA Pediatrics

324


Actual and Estimated 90-Day Pretransplant Mortalityby Pediatric End-stage Liver Disease (PELD) Score

325


Actual and Estimated 90-Day Pretransplant Mortality by Pediatric End-stage Liver Disease (PELD) Score in Each Disease Diagnosis Category at Listing

326


Conclusions

• Despite good concordance, the current PELD system significantly underestimated the true risk of death

• The precision of the PELD score to be poor, especially for children who are more sick (PELD score >20). For children with PELD scores greater than 30, the 95%CI for the likelihood of dying in 90days spanned from 23% to 43%

• Children may be disadvantaged in the current organ allocation system compared with adults, the transplant community should develop a risk estimation tool for children that allows for the direct comparison of risk of death with that among adults

327


Deceased Pediatric Donor Livers: How Current Policy Drives Allocation and TransplantationGe, L, et.al. Hepatology 2019

• 45% of pediatric donor livers were transplanted into adults: 390 adults were transplanted with pediatric organs never offered to children, while 278 children died or were delisted due to illness, which was more apparent in DSAs with low pediatric transplant volumes

• We advocate for a change to allocation policies to allow pediatric organs to be offered to national children with status 1B or Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease >15 before being offered to local/regional + circle non–status 1A adults

• Pediatric livers would be prioritized to children who have a “time-limited opportunity for growth and development and may suffer lifelong consequences if not expeditiously transplanted,” a principle that has been articulated by the OPTN/UNOS Pediatric Transplantation and Ethics Committees

328


Frequency of whole-organ in lieu of split-liver transplantation over the last decade: Children experienced increased wait time and death. Valentino, P et.al. AJT 2019

• 420 children next on the list suitable for SLT

• 333 children (79%) underwent LT, but had longer wait-times compared to 591 actual pediatric SLT recipients (median 147 days vs 44 days, P < 0.001)

• 33 of 420 children died on waitlist

• Sharing organs suitable for splitting increases the number of LT, saving more lives with careful patient selection, SLT will not be a disadvantage to the adult recipients

• With a children-first allocation scheme, SLT will naturally increase the number of allografts

329


A national mandatory-split liver policy: A report from the Italian experience. Angelico, R et.al. AJT 2019

• Since August 2015

• Children undergoing SLT increased from 49.3% to 65.8% (P = .009)

• Pediatric LT‐waiting list time dropped (229 [10‐2121] vs

80 [12‐2503] days [P = .045])

• The pediatric (4.5% vs 2.5% [P = .398]) and adult (9.7% to 5.2% [P < .001]) LT‐waiting list mortality reduced

• A national mandatory‐split policy maximizes the SLT donor resources

330


331


Patient (A) and graft (B) survival of left‐lateral segment transplantation

332


Patient (A) and graft (B) survival of extended right graft transplantation

333


Similarities and Differences in Allocation Policies for Pediatric Liver Transplantation Across the WorldFischler, B et.al. JPGN 2019

• Replies were obtained from 15 countries from 5 of the world continents.

• In children younger than 2 years mortality on the waiting list (WL)varied between 0 and 20%

• In the same age group, there were large differences in the ratio of living donor LT to deceased donor LT and in the ratio of split liver segments to whole liver

• These differences were associated with possible discrepancies in WL mortality

• Our survey suggests that although the rate of pediatric liver transplantations is quite similar between these 15 countries, there are important differences regarding organ donation rates, mortality on the waiting list for the youngest children, and the type of liver graft most commonly used

334


Donation rate per million inhabitants

335


Pediatric liver transplantations per million inhabitants younger than 18 years

336


Waiting list mortality (%), children younger than 2 years

337


Percentage of deceased donor liver transplantation (DDLT) and living donor liver transplantation in recipients younger than 2 years

338


Type of organ in DDLT recipient younger than 2 years

339


Waiting list mortality for children younger than 2 years of age in relation to pattern of allocation

a) Countries with >2/3 of LDLT and <1/3 SLT or DD

b) Countries with >2/3 SLT or DD and <1/3 LDLT

c) Countries with SLT or DD = LDLT

d) USA, where only small numbers of patients received SLT or LDLT and a majority of the transplantations are performed with whole DD livers

340


Fifteen-Year Trends in Pediatric Liver Transplants: Split, Whole Deceased, and Living Donor GraftsMogul, DB et,al. J Pediatr 2018

341


Kaplan-Meier curve of graft survival by allograft type in the first year after transplant

342


Kaplan-Meier curve of patient survival by allograft type in the first year after transplant

343


Split, Whole Deceased, and Living Donor Grafts

2002-2009

WLT SLT Size-reduced LDLT

2010-2015

WLT SLT Size-reduced LDLT

344


Conclusions

In recent years, outcomes after the use of technical variant grafts are comparable with whole grafts, and may be superior for LDLT. Greater use of technical variant grafts might provide an opportunity to increase organ supply without compromising post-transplant outcomes.

345


Key Take-Away Slide

• The pediatric pre-transplant mortality is preventable

• PELD and pediatric liver allocation needs to be adjusted

• LDLT and graft variants should be increased

346

Debate on Simultaneous Liver/Kidney Transplantation UNOS Policy: PRO POSITION

Vatche G. Agopian Associate Professor of Surgery David Geffen School of Medicine at UCLA

Since the adoption of the model for end-stage liver disease (MELD) score as the standard for donor liver allocation in the United States in 2002, there has been a significant prioritization of liver candidates with pre-existing renal dysfunction for life-saving liver transplantation (LT). Due to poor post-LT outcomes in LT recipients who remain on renal replacement therapy, and the lack of both accurate predictors of renal recovery as well as standardized OPTN policy for simultaneous liver/kidney (SLK) listing, there has been a dramatic increase in the number of SLK. In 2017, UNOS enacted policies that defined strict medical criteria to allow for SLK listing (9.7) as well as a “safety net” to allow for expedited kidney after liver transplantation for LT recipients who have sustained renal dysfunction following LT. This new policy aligns SLK listing practices with the OPTN final rule which requires standardized medical criteria in allocation policies, and aims to reduce inappropriate and futile SLK, thereby saving high-quality kidneys for select kidney transplant alone candidates while simultaneously providing a mechanism for LT recipients to receive a kidney transplant in an expeditious manner. As with any policy change, ongoing critical evaluation of the data is necessary and may inform necessary refinements of the policy.

347


AASLD/ILTS Transplant CourseThe Critically Ill Patient and Challenges in Liver Transplantation

Debate on Simultaneous Kidney/Liver Transplantation UNOS Policy: PRO

Vatche G. Agopian, MD

Associate Professor of Surgery

David Geffen School of Medicine at UCLA

348


OVERVIEW• Background

• Kidneys in the MELD Era

• Significant increase in SLK

• “The Problem”• No standardization

• “The Solution”• Policy 9.7 – Medical Criteria for SLK Listing

• Policy 8.5G – “Safety Net”

• “The Arguments”

349


BACKGROUND: SLK in the MELD EraMELD allocates livers to sickest recipients

Pre-MELD (’84-’02)

Post-MELD (’02-present)

P

Recipients, n 2678 1896

OLT, n 3218 2129

MELD 19 28 <.001

MELD ≥ 35 13% 37% <.001

National UCLA

MELD in 2011 22 38 Agopian, Ann Surg 2013

350


BACKGROUND: SLK in the MELD EraPrioritization of liver candidates with renal dysfunction

Pre-MELD (’84-’02)

Post-MELD (’02-present)

P

Recipients, n 2678 1896

Pre-LT dialysis, % 12 34 <.001

Liver/Kidney, % 2.1 6.8 <.001

Agopian, Ann Surg 2013

351


BACKGROUND: SLK in the MELD EraDramatic Increase in Number of SLK

Formica, AJT 2016

MELD introduced

* 450% increase

*

352


BACKGROUND: SLK in the MELD EraDramatic Increase in Number of SLK

Hussain, JCTH 2018

MELD introduced

* 450% increase

*

557

731

353


“The Problem”Why is this Happening???

354


“The Problem”: Increase in SLKRecognition that pre-LT Renal Dysfunction is BAD

Gonwa, AJT 2006

355

Slides are the property of the author and AASLD. Permission is required from both AASLD and the author for reuse. Ojo, NEJM,

2003

“The Problem”: Increase in SLKPost-LT Renal Dysfunction Common

356


“The Problem”: Increase in SLKPost-LT Renal Dysfunction/ESRD results in poor LT Survival

Gonwa, Transplantation 2001

357


“The Problem”: Increase in SLKPost-LT ESRD Receiving KTX do much better than staying on HD!!

Gonwa, Transplantation 2001

358


“The Problem”: Increase in SLKInability to Predict Renal Recovery

Formica, AJT 2016

359


“The Problem”: Increase in SLKNo Standardization for Listing: Transplant Center Variation

Nadim, AJT 2012

360


“The Problem”: Increase in SLKNo Standardization for Listing: SLK Recipient Variation

Formica, AJT 2016

361


“The Solution”

On August 10th, 2017 UNOS enacted policies 9.7 and 8.5G to address several critical deficiencies in

simultaneous liver kidney transplantation

362


“The Solution”: UNOS SLK PolicyPolicy 9.7 – Medical Criteria for SLK Listing

Lum E, LT 2019

363


System to allow for expedite KT following LT in 2 scenarios:

• LT recipients unexpectedly developingkidney disease/need for RRT

• LT recipients listed for SLKT but notreceiving a kidney

• To qualify, LT recipients must have GFR < 20ml/min or maintenance HD

• Register between 60 and 365 days post-LT

“The Solution”: UNOS SLK PolicyPolicy 8.5G – “Safety Net”

Lum E, LT 2019

364


“The Arguments”

365


“The Arguments”Argument # 1 – Standardizes Criteria

• Prior to the policy, there was significant variation in transplant center practices, as well as recipient characteristics.

• Clear violation of OPTN’s “Final Rule”…allocation policies must be based on sound medical judgment and standardized criteria, must seek to achieve the best use of organs and must avoid futile transplants”

366


“The Arguments”Argument # 2 – Reduces Inappropriate SLK

Adapted from Gonwa, AJT 2016

65

70

75

80

85

90

no dialysis creat>2,no dialysis on dialysis

80.6

69.868.3

73.1

69.9

74.8

LTA SLK

Survival benefit of SLK occurs only in pre-LT HD patients

3-yr

Pat

ient

Sur

viva

l (%

)n=24,173 liver

recipients

P=0.0003

367


“The Arguments”Argument # 2 – Reduces Inappropriate SLK

~60 % of patients with < 2 month dialysis!

Formica, AJT 2016

368


“The Arguments”Argument # 3 – Saves high quality kidneys

• Kidneys used in SLK allocation tend tocome from donors with lower kidneydonor profile index (KDPI) and thus havelonger expected longevity

• Of total number of SLK transplants, 49% ofdonor kidneys had a KDPI < 35% whichwould otherwise be offered to otherprioritized groups, including pediatric,young adult, or highly sensitized

Lum E, LT 2019

369


“The Arguments”Argument # 4 – Avoids Futility

+

3- working kidneys post-LT

+

0- working kidneys post-LT

370


“The Arguments”Argument # 4 – Avoiding Futility in SLK

“The highest reported median

MELD score was 39, in Los Angeles,

California (CAOP), and the lowest 20

In Indianapolis, Indiana (INOP)”

Median MELD at LT by DSARegion 5 among the highest in

the country

371



50%

60%

70%

80%

90%

100%

15-20 20-21 21-22 22-23 >23 KTA

90.70%88.50%

87%

79.50%76%

89.60%

On

e Y

ear

Kid

ney

Gra

ft S

urv

ival

(%

)

SLKT by MELD score

• Kidney allograft survival

significantly worse than

expected at higher MELD

• A failed kidney allograft

after SLKT represents loss

of 7.2 years of life if kidney

were allocated to a patient

on the kidney list

Adapted from Locke 2008 Transplantation

P=0.02

372



Lunsford, Agopian Ann Surg 2017

373


Argument # 4 –Avoiding Futility in SLK

All Patients Listed for Liver Transplants at UCLA1/1/2004 – 8/30/2014

N=3892

Study CohortN=331

Received Liver TransplantN=160 (48%)

Excluded (N=51)Actively Listed (30), Pediatric Patients (19),Multivisceral (1), Intraoperative Death (1)

SLKTN=145 (90.6%)

LTAN=15 (9.4%)

Expired Awaiting TransplantN=171 (52%)

Patients simultaneously listed for liver and kidney transplantN=382

Non-Futile SLKTN=116 (80%)

Futile SLKT(death or HD at 3mo postTx)

N=29 (20%) Lunsford, Agopian Ann Surg 2017

374



• 39% of SLKT experienced delayed graft function (DGF)

• DGF = RRT > 7 days postTx

• 20% of SLKT experienced renal allograft futility (RAF)

• RAF = Death or need for RRT at 3 mo postTx

• Futile liver transplants accounted for 72% of RAF

0 365 730 1095 1460 18250

10

20

30

40

50

60

70

80

90

100

Time Post-Transplant (Days)

Cu

mu

lati

ve

Pa

tie

nt

Su

rviv

al (%

)

Comparative Survival for SLKT Recipients Based on Renal Allograft Futility

All SLKT Recipients (n=145)Renal Allograft Futility (n=29)Non-Renal Allograft Futility (n=116)

p<0.0001


375



• 40% of SLK listed patients who underwent LTA actually recovered native renal function


376


Argument # 4 – Avoiding Futility in SLKPeri-LT factors and Association with RAF

Non RAF(N=116)

RAF(N=29) P-value

Mean STD Mean STD

Lab MELD 33.3 7.7 36.2 5.0 0.02

Days of PreTx HD 267.7 428.6 535.8 909.7 0.051

PreTx LOS (days) 18.6 19.0 30.7 19.7 0.015

Kidney Cold Ischemia Time (min) 827 329 1089 579 <0.0001

Worst IntraOp Base Deficit -8.7 5.1 -10.5 4.4 0.036

% N % N

Female Donor Gender 66.4 77 44.8 13 0.03

Instability at Transplant Completion 15.5 18 37.9 11 0.007 Lunsford, Agopian Ann Surg

2017

377


Argument # 4 – Avoiding Futility in SLKPost-LT factors and Association with RAF

Non RAF(N=116)

RAF(N=29) P-value

Mean STD Mean STD

PostTx ICU LOS (days) 15.9 17.4 38.4 42.4 <0.0001

PostTx Total LOS (days) 36 26.2 71 75.5 <0.0001

PostTx HD (days) 8.1 13.8 88.4 110.0 <0.0001

% N % N

In-Hospital Mortality 0.8 1 65.5 19 <0.0001

One Year Mortality 6.9 8 79.3 23 <0.0001

Liver Allograft Futility 2.6 3 72.4 21 <0.0001Lunsford, Agopian Ann Surg

2017

378


Argument # 4 – Avoiding Futility in SLK


• 20% of kidneys transplanted at SLKT never function (RAF).• Occurs in patients with higher medical acuity at transplant

• Occurs most commonly due to futile liver outcomes (72% oftime)

• Overall, these data suggest that renal transplant shouldbe deferred at liver transplant in patients with highmedical acuity to avoid RAF

• “Safety net” allows for deferral of KT at time of LT• Allows observation of native kidney function

• Allows prioritization of KT in LT recipients remaining on HD

379


Take-away/Key Points

1. MELD prioritization has dramatically increased the number of SLKs, but with significant variation in practices and no standardized listing criteria

2. New UNOS SLK Policy standardizes strict medical listing criteria, and defines a “safety net” provision which allows for expedited kidney after liver transplant in recipients who remain in renal failure following LT

3. Policy is essential for compliance with OPTN final rule, and aims to minimize inappropriate SLK, saves high-quality kidneys for KT recipients, and will help to minimize futile LT

4. Ongoing assessment and refinement will certainly be necessary to assure intentof the policy actually results in improved outcomes

380

Faculty, Planner and AASLD Staff Disclosures This live educational activity has been planned in accordance with AASLD and ACCME Standards of Commercial Support by members of the AASLD/ILTS Transplant Course faculty and the following planning committees: Surgery and Liver Transplantation Committee, ILTS Transplant Committee, Scientific Program Committee, and the Governing Board. As an accredited provider, AASLD requires individuals involved in the planning of continuing medical education (CME) activities to disclose all financial relationships, including those of their spouse or partner, with a commercial interest within the past 12 months. A commercial interest is defined as any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients. All conflicts of interest are resolved prior to participation. Statement on off-label and investigational use: Speakers are asked to make a reasonable effort to identify during their presentation any discussion of off-label or investigative use or application of a product or device. Financial disclosures will appear at the beginning of each session and are provided below:

AASLD/ILTS Transplant Course Faculty Disclosures Vatche Agopian Nothing to Disclose Ramon Bataller Nothing to Disclose Francois Durand Consulting: Gilead James Findlay Nothing to Disclose Yuri Genyk Consulting: Baxter Julie Heimbach Nothing to Disclose Roberto Hernandez-Alejandro Nothing to Disclose Constantine Karvellas Consulting: Mallinckrodt Pharmaceuticals Jennifer C. Lai Consulting: Axcella Health, Inc

381

Mitra Nadim Nothing to Disclose Catherine Paugam-Burtz Disclosures were not provided Elizabeth Pomfret Nothing to Disclose Sanjiv Saigal Disclosures were not provided Monika Sarkar Grant/Research Support: Zydus Pharmaceuticals Ram Subramanian Nothing to Disclose Lisa VanWagner Grant/Research Support: AMRA Medical, Gore Medical Speaking and Teaching: Salix Pharmaceuticals, Gore Medical Carmen Vinaixa Nothing to Disclose Kymberly Watt Stock Shareholder: Madrigal, Arbutus, BMS, Viking

Planner Disclosures Deniz Balci (ILTS Education Committee) Stock Shareholder: Livervision LTD, UK Meena Bansal (Governing Board and Scientific Program Committee) Data Safety Monitoring Board for Industry or Commercial Enterprise: TREAT Consortium (NIH; not commercial entity) Research Grants: Paid to institution: NIH R01 Scientific Consultant/Advisor to Industry or Commercial Enterprise, including Development of Educational Presentations: Kinetix Group; Boehringer-Ingelheim Alex Befeler (Scientific Program Committee) Stock/Stock Options with Relevant Pharmaceutical or Biotechnology Companies: Amgen long term stockholder (independently managed by CPA), Gilead long term stockholder (independently managed by CPA) Research Grants: mallinckrodt, Salix, Sillajen

382

Marina Berenguer (ILTS Education Committee) Advisory Committee or Review Panel: Gilead, Intercept, Abbvie Grant/Research Support: Gilead Speaking and Teaching: Astellas

Jorge Bezerra (Governing Board and Scientific Program Committee) Research Grants: Gilead; Shyer

Raymond Chung (Governing Board and Scientific Program Committee) Data Safety Monitoring Board for Industry or Commercial Enterprise: DSMB Alnylam Research Grants: Gilead Sciences. Abbvie, Boehringer Ingelheim, BMS, Roche, Janssen, Merck, Kaleido, Synlogic

Laurie DeLeve (Governing Board) Scientific Consultant/Advisor to Industry or Commercial Enterprise, including Development of Educational Presentations: Abbvie, Pfizer, Daiichi Sankyo, Boehringer-Ingelheim Intellectual Property Rights (Patents, Royalties, Licensing fees): 2017-230-01 US no. 62/544,589 End-organ selective MMP inhibition enhances bone marrow progenitor cell recruitment, COMPOSITIONS AND METHODS FOR AMELIORATING TISSUE INJURY, ENHANCING LIVER REGENERATION AND STEM CELL THERAPIES -(sole inventor) - Applicant: University of Southern California, GBC ref.: 6177.132445PCT

Lorna Dove (Surgery and Liver Transplantation Committee) Company: Independent Contractor: Projects in Knowledge

Bijan Eghtesad (Surgery and Liver Transplantation Committee) Research Grants: Sanofi

Michael Fried (Governing Board and Scientific Program Committee) Research Grants: AbbVie, BMS, Gilead, Merck, National Institutes of Health Scientific Consultant/Advisor to Industry or Commercial Enterprise, including Development of Educational Presentations: AbbVie, BMS, Merck, TARGET PharmaSolutions (All uncompensated) Stock/Stock Options with Relevant Pharmaceutical or Biotechnology Companies: TARGET PharmaSolutions (Maintained in independent blind trust)

Katryn Furuya (Surgery and Liver Transplantation Committee) Nothing to Disclose

David Gerber (Surgery and Liver Transplantation Committee) Scientific Consultant/Advisor to Industry or Commercial Enterprise, including Development of Educational Presentations: Organova, Inc, Medtronic, Inc.

Roberto Hernandez-Alejandro (ILTS Education Committee) Nothing to Disclose

Moira Hilscher (Surgery and Liver Transplantation Committee) Disclosures were not provided

383

Patrick Horne (Scientific Program Committee) Scientific Consultant/Advisor to Industry or Commercial Enterprise, including Development of Educational Presentations: Abbvie, Gilead, Intercept

Simon Horslen (Surgery and Liver Transplantation Committee) Research Grants: Shire

Manhal Izzy (ILTS Education Committee) Nothing to Disclose

Dong Jiahong (ILTS Education Committee) Disclosures were not provided

John Lake (Governing Board) Research Grants: CymbaBay, Data Safety Monitoring Board for Industry or Commercial Enterprise: Intercept DSMB Scientific Consultant/Advisor to Industry or Commercial Enterprise, including Development of Educational Presentations: SRTR

Josh Levitsky (Surgery and Liver Transplantation Committee) Commercial Speaker's Bureau: Gilead Scientific Consultant/Advisor to Industry or Commercial Enterprise, including Development of Educational Presentations: Novartis, Transplant Genomics Incorporated Research Grants: Novartis

Bruce Luxon (Governing Board) Data Safety Monitoring Board for Industry or Commercial Enterprise: DSMB for Baxalta; DSMB for Sparks (for treatment of Hemophilia) Leadership in related society: Board, Committee, Journal: Research Committee member for the ACG

John Magee (Surgery and Liver Transplantation Committee and Scientific Program Committee) Nothing to Disclose

Harmeet Malhi (Scientific Program Committee) Research Grants: NIH R01 NIH U01

Nancy Man (ILTS Education Committee) Nothing to Disclose

Lopa Mishra (Governing Board) Research Grants: NIH

David Mulligan (Surgery and Liver Transplantation Committee and Governing Board) Nothing to Disclose

Lauren Myers (Surgery and Liver Transplantation Committee) Disclosures were not provided

384

Mitra Nadim (ILTS Education Committee) Nothing to Disclose

Catherine Paugam-Burtz (ILTS Education Committee) Disclosures were not provided

Henrik Petrowsky (ILTS Education Committee) Nothing to Disclose

K. Gautham Reddy (Scientific Program Committee)Research Grants: CymaBay; Genfit; Intercept; Target PharmaSolutions; Arrowhead; Gilead; Durect;Commercial Speaker's Bureau: Intercept, DovaLeadership in related society: Board, Committee, Journal: Member, Training Committee: AmericanCollege of GastoneterologyScientific Consultant/Advisor to Industry or Commercial Enterprise, including Development of EducationalPresentations: Intercept

John Renz (Surgery and Liver Transplantation Committee) Disclosures were not provided

Sanjiv Saigal (ILTS Education Committee) Disclosures were not provided

Nazia Selzner (ILTS Education Committee) Nothing to Disclose

Ronald Sokol (Governing Board) Research Grants: Paid to institution: Lumena/Shire; Albireo Scientific Consultant/Advisor to Industry or Commercial Enterprise, including Development of Educational Presentations: Alexion; Albireo; Retrophin; Shire; Mirum

Grace Su (Scientific Program Committee) Intellectual Property Rights (Patents, Royalties, Licensing fees): Patent on Image analysis and Morphomics Leadership in related society: Board, Committee, Journal: Member, Clinical Guidelines Committee, AGA; Company Employee, Officer, Director : My husband and son have equity interest in Applied Morphomics and Prenovo.

Timucin Taner (Surgery and Liver Transplantation Committee) Nothing to Disclose

Norah Terrault (Governing Board) Scientific Consultant/Advisor to Industry or Commercial Enterprise, including Development of Educational Presentations: Advisory Committees or Review Panels: Dova Pharmaceuticals Research Grants: Grant/Research Support: AbbVie, Gilead, BMS, Merck

Jason Vanatta (ILTS Education Committee) Nothing to Disclose

385

Kymberly Watt (Scientific Program Committee) Expert testimony: Intercept - site- PI Gilead - site PI, co-I Conatus - site co-I Novartis - previous site PI, co author study subanalysis Pfizer- site co-I (all multicenter study related) Stock/Stock Options with Relevant Pharmaceutical or Biotechnology Companies: BMS; Arbutus; Madrigal; Viking

AASLD Staff Disclosures

Amy D'Amato Nothing to Disclose

Greg Bologna Nothing to Disclose

Katie Duggan Nothing to Disclose

Julie Deal Nothing to Disclose

Stephanie Graham Nothing to Disclose

Stephanie Grimsby Nothing to Disclose

Jessica Jessop Nothing to Disclose

Janeil C. Klett Nothing to Disclose

John Lingerfelt Nothing to Disclose

Julia Merrill Nothing to Disclose

Bette Anne Preston Nothing to Disclose

Denise Seise Nothing to Disclose

386

Documents

AASLD/ILTS Transplant Course · Satisfactory Completion . Learners must complete an evaluation form to receive a certificate of completion. Your chosen sessions must be attended in