Exceptions as the rule: Disclosures UNOS exceptions for Grant - - PowerPoint PPT Presentation

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Exceptions as the rule: UNOS exceptions for pediatric liver transplant candidates

Emily Rothbaum Perito, MD MAS Department of Pediatrics, Transplant Hepatology Department of Epidemiology and Biostatistics

Disclosures

• Grant funding for unrelated research from

Gilead.

• No disclosures related to research that will be

discussed in this presentation.

Objectives

• Explain current priority ranking system

(MELD/PELD) for pediatric liver transplant

• Understand:

– Limitations of the current system – Role of the “Non-Standard Exception”

• Discuss policy change proposals/possibilities

Priority ranking for liver transplant

March 2000: HHS Final Rule enacted, to set “priority rankings… through

• bjective and measurable medical

criteria”

Since then….how can we do this so that the system works fairly for all transplant candidates?

9/30/2016 2 MELD (>12 years) PELD (<12 years) Bilirubin Bilirubin INR INR Creatinine Albumin Age <1yo Growth failure

WAITING LIST DEATH WAITING LIST DEATH, TRANSPLANT, OR TRANSFER TO ICU

Also: MELD published, as risk score for TIPS Jan 2005: Adolescents listed as MELD + Share 15 Mar 2000: HHS Final Rule Mar 2005: Criteria for exceptions established Aug 2005: Status 1 Status 1A and 1B May 2007: Criteria for status 1B listing narrowed Nov 2010: Pediatric donors nationally to 0-11 1A before adult local 1A Feb 2012: ICU not required for 1A/1B status June 2013: Share 35 Feb 2002: MELD/PELD system implemented Jan 2016: Serum sodium added to MELD (not PELD)

ADULT DONOR Status 1A Status 1B MELD/PELD >35 MELD/PELD 29-34 Liver-Intestine MELD/PELD 15-28 MELD/PELD 15-34 Status 1A Status 1B MELD/PELD >15 MELD/PELD <15 MELD/PELD <15 MELD/PELD <15 0-10yo DONOR 11-17yo DONOR Age 0-17 Pediatric Status 1A Age 0-11 Pediatric Status 1A Adult Status 1A Adult Status 1A Age 0-17 Pediatric Status 1B Age 0-11 Age 0-17 Pediatric Status 1A Age 0-17 Pediatric Status 1A Age 0-17 Pediatric Status 1B Age 0-17 Pediatric Status 1B Age 0-11 Age 12-17 with MELD >15 Adults with MELD >15 Age 12-17 with MELD >15 Adults with MELD >15 Age 12-17 all other Adults all other Age 12-17 all other Adults all other National Age 12-17 Pediatric Status 1A Adult Status 1A Pediatric Status 1B Age 0-11 all other All remaining pediatrics All remaining adults LOCAL+REGIONAL LOCAL NATIONAL REGIONAL

LEGEND

• 8 month old female
• Cholestasis
• Failure to thrive

LAB VALUE AST 237 ALT 119 Alk phos 883 GGT 998 TB 12.9 DB 5.9 Alb 2.2 INR 1.1

How does PELD work in practice?

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PELD?

20

Median MELD score for adult, deceased donor liver transplants, 2012

*UNOS Annual Report 2012

“Non-Standard Exception Requests” (NSERs)

• Medical urgency and risk of mortality may not be

expressed by PELD/MELD

• Request for “exception points” submitted to

Regional Review Board (RRB)

– Points requested + narrative justification

• RRB members vote on whether to approve/deny

– Urgency and potential for benefit comparable to that

• f other candidates having proposed PELD/MELD
• RRB decision may be appealed on a conference

call with RRB and transplant team

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2006 review of UNOS exceptions

• 1123 pediatric liver transplants

– 441 - PELD did not determine liver allocation

• 128 multi-organ
• 118 living donor
• 27 split liver
• 168 status 1A (dx of acute liver failure)

– 682 – PELD influenced liver allocation

• 362 (53%) - calculated PELD was

NOT used to determined organ allocation

BL Shneider et al Liver Transplantation 2006;12:40-45

2015 Review of Non-Standard Exceptions

• 3,728 pediatric patients with chronic liver

disease on liver waiting list (2002-2013)

No exception requested Exception requested

Of 1,269 pediatric patients with exception requests, 90% were approved.

13mo with biliary atresia, recurrent cholangitis

• 8/24: listed for liver transplant, PELD 7
• 9/11: Exception requested for PELD 28

– 6 hospitalizations for cholangitis and bacteremia/sepsis, despite prophylactic antibiotics

• 9/16: Exception APPROVED for PELD 28
• 9/25: Completed IV Abx for cholangitis
• 10/5: Exception APPROVED PELD 35
• Cholangitis recurred IV Abx
• 10/14: Exception request: PELD 40
• 10/20: APPROVED: PELD 40
• 10/30: Living-related liver transplant….doing well!

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2015: Exceptions increase the chance of getting a liver transplant for pediatric patients What about MELD for pediatric patients?

• 13 year old female s/p 1st liver transplant in

12/2003 for biliary atresia

– 2012: Bridging fibrosis, portal hypertension – 6/2015 : AST/ALT >1000. New liver lesions (not thought HCC) and large RLQ mesenteric and retroperitoneal varices.

• 7/2/15: Relisted for transplant, MELD 19

– TB 8.3. INR 1.5, alb 3.0

• 7/2015 Persistent hepatitis and worsening

jaundice, total bilirubin 20s.

• 7/29: Exception requested for increased MELD

13 yo awaiting re-transplant

• APPEAL DENIED
• 8/6 - 8/8: New onset insulin-dependent diabetes
• 8/13 – 8/19: Encephalopathy, INR 1.7, Bili 21.3
• 8/18: Re-appealed for MELD 30 (calculated 26)
• 8/28: APPEAL DENIED
• 9/13-9/17: Fever, encephalopathy
• 9/15: Re-appealed for MELD 31 (calculated 29)
• 9/29: APPROVED for MELD 31
• 10/19-10/22: Re-admitted for low K+, long QTc
• 10/20: Exception requested for MELD 40
• 11/1: APPROVED for MELD 40
• 12/16: Transplanted, deceased donor.

Are all NSERs approved equally?

NSER Approved (n=1,060) NSER Denied (n=74) No NSER (n=1,447) p Median age at listing 2 years (0-11) 9 years (0-15) 2 years (0-11) <0.01 Biliary atresia 47% 35% 41% <0.01

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100 200 300 400 6 11 10 3 8 7 4 2 1 9 5

Total number of waitlist candidates

Region

no NSER NSER never-approved NSER approved

*

ADULT Median MELD: LOW MEDIUM HIGH

After accounting for NSERs, older children and those without biliary atresia less likely to get transplant

* Hsu et al, AJT 2015. Model accounts for NSER status, MELD/PELD, race, insurance status

Non-standard exceptions impact transplant…but do they actually impact survival?

.05 .1 .15 .2 Cumulative Incidence 1 2 3 4 5 6 Time since listing (months) NSER Approved (p=0.01) NSER Never-approved (p=0.09) No NSER (REF)

NSER approval associated with lower waitlist mortality NSER denial associated with increased waitlist mortality

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Even for children that get transplanted, NSER denial increases risk of post-transplant death

*Braun, Perito, Dodge et al. AJT 2016. Adjusted for race, diagnosis (tumor vs. other), medical condition at transplant, MELD/PELD at waitlist removal. Age not significant in UV/MV analysis.

What next? Can we improve the system? Increase NSER transparency: Analysis of NSER narrative content

• NSER narratives on 1,138 pediatric liver transplant

waitlist candidates coded for “justifications”

• Categories: examples

– Complications of liver disease: FTT, ascites, infection – Disease trajectory: risk of death, prolonged hospitalization, time on waitlist – Access limited by current status: no living donors, inadequate offers at current MELD/PELD – Standard exception category, outside standard criteria: tumors, other metabolic diseases, post-transplant complications

% of all NSER Odds of denial Associated with approval Failure to thrive 47.8 0.56* Risk of Death 39.4 0.57* Biliary complications 21.0 0.48* Associated with denial Standard category, outside criteria 34.1 1.51* Varices, bleeding not specified 24.7 1.69* Impact on other organ system (renal, bone, lung) 19.3 1.79* Impaired quality of life 9.8 3.01* Encephalopathy 9.5 2.09* Impact on other organ system: Renal 5.9 2.83* Not associated with approval or denial Complications of liver disease, any 85.9 1.07 Fluid overload (ascites, hydrothorax, anasarca) 36.9 0.87 Infection, any (cholangitis, sepsis, peritonitis, other) 34.1 0.83 Cholangitis 25.0 0.79 Prolonged Hospitalization 24.2 0.91 Varices, with bleeding 18.2 1.19

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National Liver Review Board

• OPTN/UNOS Liver and Intestinal Organ Transplantation

Committee pursuing for both pediatric and adult review boards

• Recent guidelines to clarify evidence for NSERs in

ADULTS

– Consider for exception points: Budd-Chiari, Hepatic Epithelioid Hemangioendothelioma , multiple adenomas, post-transplant late vascular complications, polycystic liver disease with severe symptoms, cirrhotic PSC with ICU admissions + resistant bacterial infection or untreatable strictures – No evidence for exception points: ascites, GI bleeding, pruritus, chronic rejection, post-transplant small-for-size

Proposed 8 district map Conclusions

• The current MELD/PELD system has limitations,

which impacts pediatric patients differentially by age, diagnosis, and region.

• For now, NSERs impact patient outcomes—use

them to advocate for your patients!

• Adjustments to the MELD/PELD and NSER system

are needed to achieve liver transplant “priority rankings… through objective and measurable medical criteria”

Thank you! emily.perito@ucsf.edu

• Hillary Braun, MD
• Sue Rhee, Phil Rosenthal
• John Roberts, Sandy Feng and UCSF Liver Transplant
• Jennifer Dodge, UCSF Liver Center
• Lisa Gallagher, Aurora Bermudez, Kathryn Smith and liver transplant

fellows

• Funding: NIH-NIDDK, UCSF Department of Pediatrics, UCSF Liver

Center, American Gastroenterological Association Emmet B. Keeffe Award