Trapianto di fegato pediatrico: valutazione dei fabbisogni e proposta di realizzazione di un algoritmo di riferimento e trattamento in regione Toscana

Università degli Studi di Pisa

DOTTORATO DI RICERCA IN FISIOPATOLOGIA CLINICA

Coordinatore: Prof. Fulvio Basolo

TESI DI DOTTORATO

PEDIATRIC LIVER TRANSPLANTATION:

EVALUATION OF CURRENT NEEDS AND PROPOSAL FOR A REFERRAL

AND MANAGEMENT ALGORITHM IN TUSCANY

TRAPIANTO DI FEGATO PEDIATRICO:

VALUTAZIONE DEI FABBISOGNI E PROPOSTA DI REALIZZAZIONE DI UN

ALGORITMO DI RIFERIMENTO E TRATTAMENTO IN REGIONE TOSCANA

Relatore:

Dottorando:

Prof. Franco Filipponi

Dr. Laura Coletti

Abstract

The Italian donation and transplantation network is organized at a regional level. Each

regional authority provides transplant care to its residents, either within its local hospitals

or referring patients to extra-regional care facilities within predefined management

algorithms. Despite its deceased donation activity, in Tuscany there is not yet any formal

pediatric LT (PLT) program. This research project aims to design a regional referral and

management algorithm for children affected with liver disease, in view of the institution of

a regional PLT center.

Recently, the scenario of PLT has been reshaped by introduction of technological

advancements, in the form of splitting liver techniques, living donor transplantation and

minimally invasive or robot–assisted liver resections. All of these issues should be

addressed to provide health care administrators and professionals thourough overview of

PLT and of the challenges related with implementation of such a practice at a regional

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Table of Contents

1. Prevalence study on pediatric liver disease in Tuscany (calendar year 2014) ... 3

1.1. Results of the epidemiological survey ... 6

1.2. Pediatric liver transplantation activity in Italy by year 2002 thru 2013 ... 16

2. Evaluation the feasibility of a pediatric liver transplantation network in Tuscany (calendar year 2015) ... 21

2.1 Description of the transplant center activity ... 21

2.1.A Listing and management of the patient on the liver transplant waiting list ……… 21

2.1.B. Pre transplant phase ... 25

2.1.C. The peri-operative phase ... 27

2.1.D. Follow up ... 29

2.2 Database ... 29

2.3. Quality control ... 30

2.3.A. Listing and managing the patient in the waiting list ... 30

2.3.B. Pre transplant phase ... 30

2.3.C. Peri-operative phase ... 31

2.3.D. Follow up ... 31

2.3.E Database ... 31

2.3.F Quality control targets ... 32

3. Resource identification (calendar year 2016) ... 33

3.2. Health care facilities ... 34

3.3. Structural, technological and organizational requirements ... 34

3.3.A. Operating room (OR) ... 35

3.3.B. Intensive care unit (ICU) ... 38

3.3.C. Stepdown floor ... 39 3.3.D. Clinic ... 40 3.4. Personnel requirements ... 41 3.4.A. Targets ... 41 3.4.B. Staffing ... 58 3.5. Economic analysis ... 59 4. Results ... 60 5. Discussion ... 62 6. Conclusions ... 65 7. References ... 67

v

Abbreviations

ABG: arterial blood gas

AISF: Associazione italiana studio fegato AuLT: Auxilliary Liver Transplant

BP: blood pressure

BSN: Bachelor of Science in Nursing CNT: Centro nazionale Trapianti

CNTO: Centro Nazionale Trapianti Operativo CRT: Centro Regionale Trapianti

CTS: Collaborative Transplant Study EKG: electrocardiogram

Hb: haemoglobin

ICU: Intensive Care Unit

LDLT: living donor liver tranplant LT: liver transplantation

MBA: Master in business administration MD: Doctor of Medicine

OR: operating room

OTT: Organizzazione Toscana Trapianti PLT: pediatric liver transplantation PNP: programma nazionale pediatrico RN: registered nurse

SLT: split liver tranplant

Background

Liver transplantation (LT) is a life-saving option for acute and chronic liver disease for

children and adults. In the last two decades, pediatric liver transplantation (PLT) has

expanded in clinical practice and is currently being performed in several centers in the

United States,1,2 Europe,3,4 and Asia.5,6

The success of PLT is due to major clinical and technological achievements:

• improvements in perioperative care and introduction of immunosuppressive agentssuitable for use in children;7

• development and clinical implementation of surgical techniques to overcome the donor shortage, such as split liver transplant (SLT) procedures,8,9 living donor

liver transplantation (LDLT),4,5,9,10 and auxilliary liver transplantation (AuLT),9,11;

• better definition of indications to PLT.12,13,15

In Italy, the transplantation and donation system is organized at a regional level, as per

the law 91 of April 1st, 1999 with PLT recipients being waitlisted nationwide in the

vii

Figure 1: Patient disposition in the Italian pediatric liver transplant program (PNP) as per

calendar year 2013. From: official data of the Italian transplant data network (Sistema Informativo Trapianti, SIT). Ref.:

www.ministerosalute.it/trapianti/C-17-pubblicazioni_2118_allegato_2. Accessed on Oct 05, 2016.

Currently, in Italy there are three major PLT programs (1 in Bergamo Papa Giovanni

XXIII Hospital; 1 in Palermo Istituto Mediterraneo per i Trapianti e le Terapie ad Alta

Specializzazione [IsMeTT], and 1 in Rome Bambino Gesù Pediatric Hospital), with other

centers (1 at University of Padua Medical School Hospital; 1 at Turin San Giovanni

Battista Le Molinette Hospital, and 1 in Milan Ca’ Granda Niguarda Hospital) performing

pediatric procedures to a smaller extent.

In Tuscany, there is no official PLT program with pediatric liver disease patients being

treated on a case-by-case basis and referred to extraregional transplant centers based

on physicians’ discretion. Institution of a PLT program at a regional level is a

long-sought-after initiative, given the high regional donation rates, which have constantly been

Programma Nazionale Trapianto Fegato Pediatrico

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higher than the national and European averages over the last decade (Fig. 2). As a

consequence, Tuscany has a huge activity in terms of adult LT (Fig. 3).

 

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Figure 2: Actual donors per million population (pmp) as per calendar year 2013

(national average, 22.2 pmp). From: official data of the Italian transplant data network (Sistema Informativo Trapianti, SIT). Ref.:

www.ministerosalute.it/trapianti/C_17_pubblicazioni_2130. Accessed on Oct 05,

ix

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Figure 3: Liver transplant activity per center in Italy as per calendar year 2013.

From: official data of the Italian transplant data network (Sistema Informativo Trapianti, SIT). www.ministerosalute.it/trapianti/C_17_pubblicazioni_2130. Accessed on Oct 05, 2016.

Implementation of a PLT program should meet both the requirements of the catchment

area population and comply with the tenets of efficacy, efficiency, and quality of modern

care. Pivotal to this initiative is implementation of a regional PLT network whereby

pediatric patients with acute or chronic liver disease of any etiology may be timely and

appropriately referred for transplant care.

In contrast to adults recipients, the pediatric population differs for indications to LT,

allocation practice, surgical techniques, immunosuppression and post-operative life-long

aftercare.13

Originally introduced as an experimental approach to acute or chronic liver disease with

very high mortality, LT has currently become a routine procedure with favorable short

x

this system is prone to a more subjective decision

making when allocating an organ and must be assessed

critically.

Due to special characteristics in infants and children,

especially concerning the inability to develop high

serum creatinine values as a marker of severe liver and

overall disease, the MELD allocation system can not be

applied for this patient group

_{. Therefore a special}

liver allocation system for patients younger than 12

years of age was developed within the UNOS network,

not including creatinine as a major component. The so

called Pediatric Model for End Stage Liver Disease (PELD)

is calculated from serum albumin, bilirubin, INR, age

at listing and failure to thrive (based on height, weight

and gender) and was implemented for pediatric liver

allocation within the UNOS network in 2002

_{. Based}

on multivariate analyses of the Studies of Pediatric

LT (SPLIT) database, the PELD score predicts the

probability of death or hospitalization to the intensive

care unit within 3 mo of listing for LT

_.

When the MELD system was introduced in the ET

network in 2007, allocation via PELD was not implemented

for pediatric liver transplant patients. Alternatively,

the so-called matchMELD was introduced, a system

comparable to the eMELD granted to defined subgroups

of adult recipients not adequately represented by the

MELD system. The initial matchMELD at the time of

listing is set at a calculated 3-mo-mortality of 35% for

children younger than 12 years of age and 15% for

children aged 12 to 16 years. Every three months (90

d), the matchMELD increases according to a calculated

increase in 3-mo-mortality of 15% (children < 12 years)

or 10% (children aged 12 to 16 years). Furthermore,

organs derived from small adults or pediatric donors

(< 46 kg body weight) are allocated with priority to

Table 1 Diseases indicating pediatric liver transplantation

₎

Cholestatic disorders Extrahepatic biliary atresia Intrahepatic biliary hypoplasia

(Alagille disease, other)

Progressive familial intrahepatic cholestasis Sclerosing cholangitis

(primary, neonatal, secondary) Nutritive-toxic cirrhosis

Caroli disease Cholangiodysplasia Congenital liver fibrosis Langerhans cell histiocytosis Acute liver failure

Metabolic, with cirrhosis Alpha 1-antitrypsin deficiency Wilson's disease Tyrosinemia Galactosemia Neonatal hemochromatosis Cystic fibrosis Glycogenosis type Ⅳ Metabolic bile acid dysfunction

Niemann-Pick's disease Gaucher's disease Metabolic, without cirrhosis Hyperoxaluria

Crigler-Najjar syndrome Urea cycle disorders

Familial hypercholesteremia type ⅡA Glycogenosis type ⅠA

Hemophilia type A, type B Protein C deficiency Wolman's disease Organic acidemia Hepatitis Hepatitis B Hepatitis C Hepatitis non-ABC Autoimmune hepatitis Neonatal hepatitis Liver tumors Hepatoblastoma

Hepatocellular carcinoma Fibrolamellar carcinoma Hemangioendothelioma Various Budd-Chiari syndrome

Cryptogenic liver cirrhosis Infantile copper overload

Transplant year LT Pediatrics 0-14 yr 2010-13 n = 1192 2005-09 n = 2030 2000-04 n = 1765 1995-99 n = 1606 1990-94 n = 1628 1985-89 n = 658 0 1 2 3 4 5 Time post-transplant (yr)

P < 0.001 CTS 100 90 80 70 60 50 40 30 20 10 0 Graft survival (%)

Figure 1 Development of graft survival after pediatric liver transplantation

from 1985 until 2013 (collaborative transplant study data). CTS: Collaborative

transplant study; LT: Liver transplants.

CTS 100 90 80 70 60 50 40 30 20 10 0

Recipient age of pediatrics patients (%)

Transplant year - recipient age LT Pediatrics 0-17 yr 1985 -1989 n _{= 737} 1990 -1994 n _{= 1824} 1995 -1999 n _{= 2017} 2000 -2004 n _{= 2236} 2005 -2009 n _{= 2409} 2010 -2013 n _{= 1956} P < 0.001 9.9 27.4 53.7 9.0 10.3 27.6 42.4 19.7 12.0 27.0 41.2 19.7 12.4 28.6 33.2 25.8 9.3 27.7 37.9 25.0 9.0 25.3 39.0 26.7 15-17 6-14 1-5 0

Figure 2 Age distribution of pediatric liver transplantation recipients from

1985 until 2013 (collaborative transplant study data). CTS: Collaborative

transplant study; LT: Liver transplants.

Hackl C

et al

. Current developments in pediatric liver transplantation

Figure 4: Graft survival of pediatric liver transplantation 1985 thru 2013 (Data source:

the Collaborative Transplant Study data, CTS).13,14

Every effort should be made to help medical institutions treating pediatric populations to

further improve the long-term outcome and quality of life of PLT recipients, also due to

LT being an extremely expensive procedure requiring lifelong drug administration.

Available data confirm that PLT for patients in relatively good conditions and favorable

nutritional status provides better outcomes than for very sick recipients.15,16,17

Implementation of a pediatric regional network requires coordination of care facilities

involved in the management of the pediatric liver disease populations, but also

identification of the prevalence and incidence of pediatric liver disease, of current

migration algorithms, and of barriers that may hamper or hinder the initiative.

The current research project is aimed at paving the way for institution of a PLT program

in Tuscany through identification of the current state of the art on pediatric liver disease

at a regional level; identification of all care facilities involved in management and referral

xi

algorithms, as well as recognition of the technical and resource capacities necessary for

Introduction

This was a prospective, three-tiered research program within the scope and activities of

the Region Tuscany donation and transplantation network and in collaboration with the

Azienda Ospedaliero Universitaria Pisana, Pisa University School of Medicine, and the

Azienda Ospedale Pediatrico Meyer in Florence. The program was carried out in

compliance with the principles set forth in the 2013 revision of the Declaration of

Helsinki.18

The primary research program endpoints were:

• Assessment of the prevalence of pediatric liver disease in Tuscany;

• Assessment of the prevalence of pediatric liver disease patients eligible for LT in Tuscany;

• Identification of health care facilities and institutions in charge of pediatric liver disease patients in Tuscany;

• Identification of current migration algorithms of pediatric liver disease patients; • Designing of a regional PLT network to be implemented in Tuscany;

• Preliminary economic analysis of such a PLT program. The secondary research programs endpoints were:

• Identification of prevalent pediatric liver disease etiologies in Tuscany; • Evaluation of patients’ and families’ needs and priorities;

• Identification of structural and human resources instrumental to implementation of a PLT care program in Tuscany;

• Exploration of quality of life of pediatric liver disease patients and their families; • Exploration of social attitudes toward implementation of a pediatric liver disease

2

The reference models used for implementation of the program are the ecological and the

chronic care models. The ecological model posits that 3 levels are to be included in

health care organizations:

1. The micro-level: i.e. patient-to-provider interaction;

2. The meso-level: i.e. health care organizations;

3. The macro-level: i.e. society, politics and legislation.

The chronic care model posits that the outcome of health care intervention requires a

proactive care team combined with expert patients and families.

The research program has encompased 3 successive phases:

1. Phase 1: prevalence study on pediatric liver disease in Tuscany (calendar year

2014);

2. Phase 2: design of a PLT network in Tuscany (calendar year 2015);

1. Prevalence study on pediatric liver disease in Tuscany (calendar year

2014)

This study consisted of evaluation of the prevalent causes of liver disease in pediatric

populations and of a formal epidemiological research study on prevalence and incidence

of pediatric liver disease in Tuscany (Tab. 1, 2). The study used formal epidemiological

tools and was based on the official regional and national registries of pediatric liver

disease as well as on the reports from the Italian National Center for Transplantation

(Centro Nazionale Trapianti, CNT).

Concurrent with this, we proceeded with evaluation of the migration algorithms through

use of the Tuscany registry for orphan disease. The economic analysis was performed

4

Cholestatic disorders Extraepatic biliary atresia

Intrahepatic biliary hypoplasia (Alagille disease, other) Progressive familial intrahepatic cholestasis

Sclerosing cholangitis (primary, neonatal, secondary) Nutritive-toxic cirrhosis

Caroli disease Colangiodysplasia Congenital liver fibrosis Langerhans cell histiocytosis Acute liver failure

Metabolic, with cirrhosis Alpha 1-antitrypsin deficiency Wilson’s disease Tyrosinemia Galactosemia Neonatal hemochromatosis Cystic fibrosis Glycogenosis type IV

Metabolic bile acid dysfunction Niemann-Pick’s disease Gaucher’s disease Metabolic, without cirrhosis Hyperoxaluria

Crigler-Najjar syndrome Urea cycle disorders

Familial hypercholesterolemia type IIA Glycogenosis type IA

Hemophilia type A, type B Protein C deficiency Wolman’s disease Organic acidemia Hepatitis Viral hepatitis B, C, other

Autoimmune hepatitis Neonatal hepatitis

Liver tumors Hepatoblastoma

Fibrolamellar carcinoma Hemangioendothelioma

Various Budd-Chiari syndrome

Cryptogenic liver cirrhosis Infantile copper overload

Hepatitis Viral hepatitis B, C, other Autoimmune hepatitis

Pharmacological (e.g. acetaminophen) Liver disease associated with

chronic inflammatory bowel disease

Sclerosing cholangitis

Liver tumors Hepatoblastoma

Fibrolamellar carcinoma Hemangioendothelioma Hepatocarcinoma Disease associated with fatty

liver

Fatty liver of obesity (nonalcolholic stestohepatitis) Fatty liver of pregnancy

Various Wilson’s disease

Budd-Chiari syndrome and Veno-occlusive disease Hypotension/ischemia/cardiac failure

Parasitic infections Drugs and toxins

Table 2: classification of pediatric liver diseases affecting older children and adolescents and according to reference 12.

6

1.1. Results of the epidemiological survey

The results of the Phase 1 epidemiological survey are presented in Tables 3 and 4 and

in Figures 5 thru 13.

Disease N

Biliary atresia 46

Alagille’s syndrome 22

Progressive familial intrahepatic cholestasis syndrome type 1 1

Progressive familial intrahepatic cholestasis syndrome type 2 2

Progressive familial intrahepatic cholestasis syndrome type 3 4

Byler’s disease 1

Alfa-1-antitrypsin deficiency 18

Budd-Chiari’s syndrome 2

Primary Sclerosing Cholangitis 29

Urea cycle defects 52

Gaucher’s disease 38

Glycogen storage disease 53

Wilson’s disease 41

Idiopatic neonatal fibrosis 1

Niemann-Pick disease 3

Crigler-Najjar syndrome 32

Tyrosinemia 4

Zellweger syndrome 2

Table 3: pediatric liver disease patients reported to the Tuscany registry for orphan

disease 2000 thru 2013. Data of the Tuscany registry for orphan disease available at may 04, 2014.

Disease Patients referred to Tuscany Region N (%)

Biliary atresia 13 (27.7)

Alagille’s syndrome 16 (73.9)

Progressive familial intrahepatic cholestasis syndrome type 1 0 (0)

Progressive familial intrahepatic cholestasis syndrome type 2 2 (100)

Progressive familial intrahepatic cholestasis syndrome type 3 1 (25)

Byler’s disease 0 (0)

Alfa-1-antitrypsin deficiency 14 (7.7)

Budd-Chiari’s syndrome 0 (0)

Primary Sclerosing Cholangitis 14 (5)

Urea cycle defects 14 (26.3)

Gaucher’s disease 13 (35)

Glycogen storage disease 12 (22)

Wilson’s disease 0 (0)

Idiopatic neonatal fibrosis 0 (0)

Niemann-Pick disease 0 (0)

Crigler-Najjar syndrome 19 (58.8)

Tyrosinemia 1 (25)

Zellweger syndrome 0 (0)

Table 4: pediatric liver disease patients reported to the Tuscany registry for orphan

disease 2000 thru 2013 and referred to Tuscany Region from extraregional institutions. Data of the Tuscany registry for orphan disease available at may 04, 2014.

8

Registro della Rete Toscana delle Malattie

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Figure 5: breakdown analysis of all cases of biliary atresia reported to the Tuscany

registry for orphan disease 2000 thru 2013. Data of the Tuscany registry for orphan disease available at may 04, 2014.

Registro della Rete Toscana delle Malattie

Rare

Figure 6: breakdown analysis of all cases of Alagille’s syndrome reported to the

Tuscany registry for orphan disease 2000 thru 2013. Data of the Tuscany registry for orphan disease available at may 04, 2014.

10

Registro della Rete Toscana delle Malattie

Rare

Figure 7: breakdown analysis of all cases of intrahepatic progessive familiar cholestasis

(IPFC also known as bening recurrent familiar cholestasis (BRIC)) and Byler’s disease reported to the Tuscany registry for orphan disease 2000 thru 2013. Data of the Tuscany registry for orphan disease available at may 04, 2014.

Registro della Rete Toscana delle Malattie

Rare

Figure 8: breakdown analysis of all cases of alpha1-antitrypsin deficiency reported to

the Tuscany registry for orphan disease 2000 thru 2013. Data of the Tuscany registry for orphan disease available at may 04, 2014.

Registro della Rete Toscana delle Malattie

Rare

Figure 9: breakdown analysis of all cases of pediatric Budd-Chiari syndrome and

Primary Sclerosing Cholangitis reported to the Tuscany registry for orphan disease 2000 thru 2013. Data of the Tuscany registry for orphan disease available at may 04, 2014.

12

Registro della Rete Toscana delle Malattie

Rare

Figure 10: breakdown analysis of all cases of urea cicle defects reported to the Tuscany

registry for orphan disease 2000 thru 2013. Data of the Tuscany registry for orphan disease available at may 04, 2014.

Registro della Rete Toscana delle Malattie

Rare

Figure 11: breakdown analysis of all cases of Gaucher’s disease reported to the

Tuscany registry for orphan disease 2000 thru 2013. Data of the Tuscany registry for orphan disease available at may 04, 2014.

14

Registro della Rete Toscana delle Malattie

Rare

Figure 12: breakdown analysis of all cases of glycogenosis reported to the Tuscany

registry for orphan disease 2000 thru 2013. Data of the Tuscany registry for orphan disease available at may 04, 2014.

Registro della Rete Toscana delle Malattie

Rare

Figure 13: breakdown analysis of all cases of Wilson’s disease reported to the Tuscany

registry for orphan disease 2000 thru 2013. Data of the Tuscany registry for orphan disease available at may 04, 2014.

16

1.2. Pediatric liver transplantation in Italy by year 2002 thru 2013

Data on the PLT activity in Italy are reported in Figures 14 thru 16.

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Pediatric liver transplantation in Italy by year

Liver Tranplant Activity 2002-2013

Total: 784

Figure 14: the PLT activity in Italy 2002 thru 2013. From: official data of the Italian

transplant data network (Sistema Informativo Trapianti, SIT).

www.ministerosalute.it/trapianti/C_17_pubblicazioni_2118_allegato_2. Accessed on Oct

SIT Sistema Informativo Trapianti

Fonte Dati: SIT Centro Trapianto N Trapianti BERGAMO 20 ROMA OPBG 11 PADOVA 9 ISMETT 8 TORINO 7 MILANO 2 Totale 2013 57

Attività di Trapianto anno 2013

Programma Nazionale Pediatrico FEGATO

Figure 15: the PLT activity in Italy in 2013 by center. From: official data of the Italian

transplant data network (Sistema Informativo Trapianti, SIT).

www.ministerosalute.it/trapianti/C_17_pubblicazioni_2118_allegato_2. Accessed on Oct

18

SIT Sistema Informativo Trapianti

Fonte Dati: SIT

Programma Nazionale Pediatrico

FEGATO

Attività di Trapianto 2002 31/12/2013

Classe di età dei pazienti al trapianto

Figure 16: the PLT activity in Italy in 2013 by recipient’s age. From: official data of the

Italian transplant data network (Sistema Informativo Trapianti, SIT).

www.ministerosalute.it/trapianti/C_17_pubblicazioni_2118_allegato_2. Accessed on Oct

As of presentation of these data (March 24, 2015), the total of Tuscan pediatric patients

waitlisted in the Italian national list (PNP) from 2001 was 53, with a mean age of 5.2

years (<3 years = 62.2%) (official data received by the CNT). Among these, 43 patients

were transplanted (2 with LDLT grafts), 3 died while on the list, 4 were delisted, while 3

were still on the waiting list at the time of data transmission.

Table 5 illustrates the PLT performed on Tuscan pediatric children by national centers

from 2001 thru 2013.

LT centers

Procedures (n)

Bergamo 30

Palermo ISMETT 12

Rome Bambin Gesù 4

Padua 3

Pisa 3

Turin 1

Table 5: PLT procedures performed on Tuscan children 2001 thru 2013. Offcial data of

the CNT.

The indications to PLT in such population are reported in Table 6.

20

Indication to LT Patients (n)

Biliary atresia 7

Other Cholestatic disease 3

Primary Biliary Cirrhosis 2

Primary Sclerosing Cholangitis 1

Metabolic disease 3 Viral hepatitis 1 Other hepatitis 8 Cystic fibrosis 1 Malignancies 3 Re-LT 3 Unknown 21

Table 6: Indications to PLT procedures performed on Tuscan children 2001 thru 2013.

2. Evaluation the feasibility of a pediatric liver transplantation network in

Tuscany (calendar year 2015)

It consisted of drafting of a regional pediatric liver transplantation network. This resulted

in:

§ Definition of care facilities to be involved in the integrated network, from general

practitioners to third-level health care;

§ Definition of referral guidelines, in view of timeliness, efficacy, efficiency,

appropriateness, and quality of care;

§ Definition of management algorithms, with special focus on emergencies,

urgencies, palliative care, malignancies, and rescue treatment;

§ Identification of quality assurance policies to be shared by all participants and

enforced at all network levels, under the scrutiny of the regional competent

authority (Organizzazione Toscana Trapianti, OTT)

2.1. Description of the transplant center activity

2.1.A. Listing and management of the patient on the liver transplant waiting list 2.1.A.I. Patient evaluation (Figure 17)

The transplant center medical team is responsible for evaluation of patients’ eligibility to

transplantation and assuring that:

• they are in a condition of progressive, terminal and irreversible organ failure; • they match the indications for liver transplantation;

• no absolute contraindication to solid organ transplant is present;

• the family members are able to understand and accept the risks and benefits of the procedure.

22

2.1.A.II. Patient selection

All patients are evaluated by a committee including the members of the transplant

center (transplant center committee, TCC) and the consultants of the Units cooperating

with the transplant center (anesthesiology, pediatrics, neonatology, neurology,

pneumology, cardiology, infectious disease, diabetology, gynecology, psicology,

radiology, microbiology, laboratory and pathology) in order to:

• stage the patient’s disease;

• request additional tests if needed, and according to evidence-based guidelines; • decline the patient from transplantation if contraindications exist.

The patient should be referred to the transplant center by referral units (e.g.: pediatrics,

hepatology, gastroenterology, etc…) selected in the regional area.

Referral Unit Transplant Center Committee Director of Liver Transplant Unit

Patient evaluation Is the patient eligible to LT? CRAOT Evaluation of clinical case Management of patient on the waiting list

FLOW CHART #1 EVALUATION FOR STANDARD PATIENTS

Appoint TCC Coordinator and plan the meeting LTU Alternative options Can the patient be waitlisted? CNTO Yes No No LT: trapianto di fegato LTU: Centro Trapianti TCC: Transplant Center Commitee CNTO:

Centro Nazionale Trapianti Operativo

CRAOT: Centro Regionale Allocazione Organi e Tessuti

DOCUMENTS for LISTING:

-Patient presentation form -Committee meeting reports

-Surgical consent form -Patient/Family information notes

Yes

Yes

2.1.A.III. Waitlisting (Figure 18)

The TCC members discusses the clinical cases on the basis of the available records

and opt for:

• waitlisting of the patient;

• declining the patient from waitlisting;

• requesting additional tests prior to final decision.

The TCC should meet weekly and the decisions written and communicated to the

referral unit. All of the written reports should be recorded. The waiting list is divided in 4

sections according to ABO blood groups.

The patient is dynamically kept in the waiting list. Their status can be modified

(exclusion; readmission; temporary withdrawal), based on their clinical status.

At the time of waitlisting, the TCC defines the priority of the candidate based on the

clinical situation. Every week the TCC must redefine this priority after review of the

candidate clinical status.

Category Sub-category Frequency

STATUS* 1 Fulminant hepatic failure weekly PNF (Primary Non Function) within 7 days after transplantation weekly Hepatic artery thrombosis diagnosed within 14 days after transplantation weekly

Acute hepatic failure in Wilson disease weekly

An-hepatic condition weekly

STATUS* 1B Hepatoblastoma No deadline

Hepatocellular carcinoma No deadline

Hemangioendothelioma No deadline

STATUS* 2A chronic liver disease with PELD/MELD ≥25+mechanical ventilation weekly chronic liver disease with PELD/MELD ≥25+gastrointestinal bleeding weekly chronic liver disease with PELD/MELD ≥25+haemodialysis or haemofiltration weekly chronic liver disease with PELD/MELD ≥25+Glasgow coma scale ˂10 weekly

STATUS* 2B Metabolic diseases with neurological risk - Crigler Najjal No deadline Metabolic diseases with neurological risk - Urea cycle disorders No deadline Metabolic diseases with neurological risk - Organic acidemia No deadline Metabolic diseases with neurological risk - Leucinosis No deadline Metabolic diseases with neurological risk - Wilson disease No deadline

EXCEPTIONS* PELD/MELD Metabolic diseases without prevalent neurological risk - Type I hyperoxaluria No deadline after three months

Score PELD/MELD after 3 months in 2B Metabolic diseases without prevalent neurological risk - Familiarl hypercholesterolemia No deadline after three months Metabolic diseases without prevalent neurological risk - H-factor mistake in Hemolytic uremic syndrome No deadline after three months Hepato-Pulmonary syndrome No deadline after three months Porto-Pulmonary hypertension No deadline after three months PELD/MELD > 25 Deadline after 14 days PELD/MELD < 25 e > 15 Deadline after 90 days PELD < 15 Deadline after 365 days * The waiting list time for the EXCEPTIONS is calculated according to the Exception onset date that can never be antecedent to the inscription date

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2.1.A.IV. Management of the patient on the waiting list

The transplant center is bound to schedule their waitlisted patients’ follow up. The

follow up protocol should be drafted locally and shared by all referring Units.

2.1.A.V. Management of the acute organ failure (Figure 19)

The patient with acute organ failure is referred to the transplant center. The transplant

center evaluates the patient and admits them to the transplant hospital. The TCC

communicates the case to the regional transplant center (Centro Regionale Trapianti,

CRT) which will transfer communication to the CNTO (Centro Nazionale Trapianti

Operativo) for nationwide listing.

A protocol for definition and management of the acute organ failure patient should be

drafted according to international, evidence-based guidelines19,20_{. Acute hepatic artery}

thrombosis and primary non function of the liver graft can be considered acute failure

Referral Unit LT Unit/ICU CRAOT _CNTO Patient referral Report to Regional Centre Patient evaluation Indication for OLT Yes Urgent Liver Transplantation Monitoring and alternative treatments

FLOW CHART # 2 PEDIATRIC ACUTE LIVER FAILURE

Report to National Centre No LTU: Liver Transplant Unit ICU: Intensive Care Unit CNTO: Centro Nazionale Trapianti Operativo CRAOT: Centro Regionale Allocazione Organi e Tessuti OLT: Orthotopic Liver Tranplant Organ allocation Organisation of Liver Procurement

Figure 19: Flow Chart #2 Management of pediatric acute liver failure.

2.1.B. Pre transplant phase (Figure 20) 2.1.B.I. Choice of the transplant candidate

The TCC defines the priority for patients on the waiting list at weekly intervals and on

the basis of a predefined protocol (e.g.: pediatric model for end-stage liver disease

(PELD), Child-Pugh, United Network for Organ Sharing (UNOS) stata, etc…). Once an

organ becomes available, the patient will be selected according to the national priority

list. If the surgeon on call decides not to transplant the patient who is on top of the list,

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2.I.B.II. Evaluation of the donor, and the donor-to-recipient matching

There must be clear definition of all clinical duties. The transplant coordinator at the

local hospital makes sure that the formal requirements for brain death are met,

explores their suitability for donation, and obtains the consent from the next of kin

according to the law. Once the donor is considered suitable for donation, the CNTO

offers the liver graft to a national transplant center according to a predefined algorithm.

The CNTO also schedules procurement surgery and the CRT is in charge of shipping

blood samples to laboratories for function tests, immunological analysis, and infectious

disease screening. The liver transplant centre arranges transfer of the surgical team for

organ procurement, while the CRT and/or CNTO will provide flights in case of distant

procurement sites.

ICU CRAOT/CNTO LTU

Potential brain dead

donor

Brain death declaration Committee (CAM) and family interview

Are there any urgencies? Is the patient suitable for organ

donation?

FLOW CHART # 3 LIVER ALLOCATION TO STANDARD PATIENTS

Report to LTU CRAOT/CNTO

Stop

Allocation of the liver and coordination of organ shipping and procurement teams

Accept

Refusal

CAM: Commissione Accertamento Morte LTU: Centro Trapianti CNTO:

Centro Nazionale Trapianti Operativo

CRAOT: Centro Regionale Allocazione Organi e Tessuti

No Yes Donor and recipient evaluation Organisation of liver procurement

2.1.C. The peri-operative phase

2.1.C.I. The anesthesiological evaluation

The liver transplant recipient is admitted to the transplant center by the on-call surgeon.

The anesthesiologist has already evaluated this patient before his entry on the waiting

list. However, due to interval between waitlisting and transplantation, the recipient

requires updating of the anesthesiological evaluation and eligibility to surgery. A

protocol for the pre-operative work-up should be drafted. Patients with acute organ

failure are an exception to this practice.

2.1.C.II. Surgical activity (Figure 21)

The recipient surgical team starts transplantation after anesthesiological evaluation and

suitability of the liver graft has been confirmed.

Mandatory protocols to be drafted and implemented are:

• Operation room set-up;

• Patient preparation for surgery; • Patient set-up in the operating room; • Intra-operative patient monitoring.

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Anesthesiologist Surgeons Backtable Other teams/services involved

Patient preparation Liver graft inspection Abdominal wall incision Hepatectomy Graft implantation Suture of the abdominal wall ICU* Patient monitoring Cholangiography Backtable Procedure (Figure)

FLOW CHART # 4 RECIPIENT’S SURGERY

Starts at the end of flow chart #3

*ICU: Intensive Care Unit

Figure

Figure 21: Flow Chart #4 Recipient’s surgery. 2.1.C.III. ICU management

The ICU team takes care of the patient immediately after transplantation. The surgical

and anesthesiological team provide a detailed report on the procedure. Eventually, the

on-call intensivist takes responsibility for verifying that the medical treatment has been

scheduled correctly.

2.1.C.IV. Step-down wards

The surgical team is responsible for patients’ care in the step-dowm wards. On a

routine basis, physicians (anesthesiologists, gastroenterologists, pediatricians, etc…)

cooperate with the surgical team. The patient is followed up according to

standard-of-care protocols with regard to clinical examinations, immunosuppression, infectious

2.1.D. Follow up

The transplant team is responsible for the post-transplant follow up. After the patient is

discharged, the surgical team will follow up the patient for as long as needed to

stabilize the clinical conditions (i.e. approximately one year). After this period the

patient can be referred to a selected medical team, but the transplant team should

keep records of the patient status according to a pre-defined follow-up protocol. The

transplant team should also update a database with all patients’ follow up information.

A post-transplant clinic should be set up in the transplant center in view of following up

patients in the post-transplant period. The transplant nurse coordinator should

schedule the appointments for the patient and according to a pre-defined follow-up

protocol.

In the post-transplant clinic the transplant team should:

• Visit the patient; • Obtain blood tests;

• Request medical consultations (scheduled or on demand); • Evaluate lab tests and adjust patient’s treatment;

• Draft a clinical report for the patient’s general practicioner and referral physician;

• Admit the patient to in-hospital care if needed.

Agreement should be reached between the transplant center and the referring Units to

share duties and responsibilities.

2.2. Database

Complete donor, transplant, and patient records should be stored in an electronic

database. Graft and patient data should be collected, controlled and made promptly

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2.3. Quality control

Protocols for every procedure should be drafted by the transplant center in order to

guarantee operation of routine activities. Some protocols can be obtained by scientific

societies, while others should be prepared locally.

2.3.A. Listing and managing the patient in the waiting list

Protocols Documents

Indication to liver transplantation Contraindication to liver transplantation Pre-transplant patient evaluation Priority allocation flowchart

Local protocol for the transplant center committee meeting

Local protocol for acute hepatic failure management Local protocol for patient/family information about listing and organ allocation criteria

Local protocol for pre-transplant patient follow-up

Patient presentation form Committee meeting reports Surgical consent form

Patient/Family information notes

2.3.B. Pre-transplant phase

Protocols Documents

Local protocol for organ and donor evaluation (extended criteria donor acceptance and allocation) Local protocol for organ procurement

2.3.C. Peri-operative phase

Protocols Documents

Anesthesiological protocol

Local OR (Operating Room) preparation protocol Local patient preparation protocol (in the wards, in OR) Patient intraoperative biochemical monitoring

ICU patient management and monitoring Post-operative biochemical monitoring Complication management

OR procedures (transplant report, anesthesiological report, etc…)

2.3.D. Follow-up

Protocols Documents

Post-operative follow-up management Rotation, schedule and personnel

2.3.E. Database

Protocols Documents

Pre, peri and post-operative patients’ data Surgical records

Every change to these protocols must be discussed and approved by the transplant

center committee meeting. The chief of the transplant center is in charge for scheduling

the mortality and morbidity meetings and for verification of the application of the

adopted protocols.

The personnel should be encouraged to participate to congresses and meetings under

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2.3.F. Quality control targets

Target Performance indicators

Define responsibilities, competencies and develop internal communication

Participation to the transplant center committee meetings or research groups Offer citizenship the opportunity to receive a

transplant

Number of patients evaluated for transplant

Offer patients the opportunity to receive a transplant in a reasonable amount of time

Mean/median waiting list time

Allocate the organ on the basis of pre-defined and agreed criteria

Preparation and adherence to specific protocols

Improve the efficiency of organ allocation system Number of transplants/number of available organs

Decrease the incidence of re-transplantation Number of re-transplants/number of transplants in a year

Decrease the waiting list mortality Number of patients deceased in the waiting list in a year/number of transplants in a year

Obtain national and international recognition in the transplant field

Scientific publication in peer reviewed journals and communications in scientific meetings

Achievement of the quality control targets

3. Resource identification (calendar year 2016)

It consisted of identification of necessary resources. This resulted in:

§ Assessment of current competence level of health care professionals and

census of facilities meeting formal requirements for pediatric liver transplant

care;

§ Assessment of educational need and gaps and identification of

strategies/policies to meet the demand;

§ Assessment of technical requirements, in view of existing technology and of that

required for a pediatric liver transplant program;

§ Economic analysis, based on the available international literature.

This will require adjustements in

• Organization • Logistics

• Health care facilities • Technical resources • Staffing

3.1. Organization and logistics:

• Implement an operational network for referral of pediatric liver disease and centered on the regional pediatric hospital center in Florence

• Implement a surgical referral network between the pediatric liver disease and the transplant centers (Florence > Pisa)

• Implement a surgical discharge pathway between the transplant and pediatric liver disease centers (Pisa > Florence)

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3.2. Health care facilities:

• Reorganize pediatric care by providing children-oriented facilities adjacent to current adult liver transplant patients care

o operating room

o wards

o supplemental rooms for family members and care givers

• Adapt/expand technical resources to allow for care of the pediatric population o beds

o intubation materials and ventilators

o hemodynamic control kits

o diagnostic tools

3.3. Structural, technological and organizational requirements:

In order to provide the best treatment options, the following competencies should be

available in a transplant center: 15

1. Surgeon

2. Pediatric hepatologist

3. Anesthesiologist and critical care specialist

4. Infectious disease specialist

5. Nutritionist/Dietician

6. Neuropsychologist and child developement specialist

7. Rehabilitation physician

8. Transplant coordinator

9. Transplant nurses

Moreover, the following physicians should be available as consultants: 1. Cardiologist 2. Pneumologist 3. Nephrologist 4. Diabetologist 5. Neurologist 6. Psychiatrist 7. Radiologist 8. Endoscopist 9. Pathologist

The department of Radiology, Infectious disease, Pathology, and Laboratory medicine

should work in strict connection with the transplant center. They should give specific

consultation in the different phases of the transplant process.

3.3.A. Operating room (OR)

The operating room must be authorized to perform organ transplantation by local

authorities. The surgical unit should be close to the laboratories facilities, and a small

area with the possibility to perform blood test (e.g. blood gas analysis) should be

present in the OR floor. Moreover, the following requirements are mandatory:

I) Structural requirements: 21,22

• Adequate size room. The suggested surface area is 36m2. _{The minimum}

acceptable surface area for highly specialized surgery is 30 m2. A minimum of

two operating rooms is required;

• The corridor for patient transfer should be at least 2 meters wide; • A filter room for the patient;

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• A recovery room. The minimum surface area is 9 m2 _{per bed;}

• A scrub room;

• Male and female looker rooms with restrooms; • A sterilization and decontamination room; • A room for surgical devices storage; • A room for contaminated material storage; • A room dedicated to coordination activities;

• A phone line, web connection, and on line connection with the laboratory and radiology must be available in the OR;

• Adequate air conditioning system

II) Technological requirements23

Device Notes

Anesthesia device with comprehensive

monitoring capabilities and integrated with a ventilator

Possibility of closed circuit ventilation with low flow

EKG monitor with at least two derivations always under vision and continuous ST analysis

Invasive pressure measurements device for -radial or femoral arterial pressure

-pulmonary arterial pressure -central vein pressure

Non invasive pressure measurement device Temperature control device (2)

SpO2 measurement (if not present in other devices)

The instruments should be equipped for data recording in order to document the most significant events of the procedures

Video to monitor all the main anesthesia variables

Portable monitor to be used for patient transfer in ICU

EKG, BP and SpO2 must be continuously visualized

Adequate number of pump syringe devices for drugs administration

Pediatric Intubation set

A set for bronchoscopy, laringoscopy and other tracheal-broncoscopy procedures for pediatric population

Arterial blood gas analysis machine For ABG, electrolytes, Hb, and glycemia control

Blood bank For temporary blood product storage

Pump for the extracorporeal intra-operative veno-venous bypass

Surgical instruments

Adequate illumination, ceiling and air supply system

Defibrillator

III) Staff requirements

An anesthesiologist with expertise in transplantation is required. The presence of

another anesthesiologist is strongly suggested.

A technician should help the anesthesiologist in the proper patient management and

monitoring and for the preparation of the patient in the pre-operative phase.

Three nurses are required for the proper management and preparation of the OR.

A fourth person is required to communicate with the other services and to transfer the

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3.3.B. Intensive care unit (ICU)

I) Structural requirements21

The ideal ICU should have at least 6 beds. Two beds can be considered the minimum

acceptable number. The ICU can be structured as an open space or with single bed

boxes. An optimal view of the patients must be provided. The minimum surface area for

each bed place is 20 m2 _{if organized as a single box or 15 m}2 _{if organized as an open}

space. The minimum distance between each bed should be 2.5 meters. The total

surface area of the ICU should be at least 2.5 times the area dedicated to the bed

places. Moreover, the following requirements should be fulfilled:

• The ICU should have the same air conditioning system requirement of the OR; • A room for the on call physician;

• A locker room for the personnel with restrooms; • A filter room for the personnel;

• A working station for the nurses with comprehensive monitoring capabilities; • A working station for physicians;

• Washing devices for each bed; • Clean material storage room;

• Contaminated material storage room;

• The surface area per bed place should be enough to allow: o The use of warming device for the patient

o To perform a bed ultrasound scan

o To dialyze the patient

o To perform portable x ray

o To perform regular dressings of the wound

II) Technological requirements

• Anti ulcer bed • Ventilator • Suction device • Coagulator • Defibrillator

• A scale for the patient weight • Adequate number of pump syringes • Adequate light sources

• Mechanical support for the pump syringes • Monitoring systems for:

o Cardiac output

o Non invasive pressure

o EKG

o SaO2

III) Staff requirements

• A dedicated physician and nurses should be present at the time the patient is admitted in the ICU;

• Surgeon and internal medicine doctor should visit the patients daily;

• Dedicated nurses should take care of the patient till he/she needs advanced cares;

• A physician should be present 24/7

3.3.C. Stepdown floor

40

children aged < 3 year). The surface area should be at least 9 m2. They must have an

adequate air conditioning system. Each room should have a bathroom included.

Nursing assistance should be provided 24/7. A physician should be on call 24/7.

Moreover the following rooms should be present:

• A locker room for the personnel with restrooms • A working station for the nurses with PCs • A working station for physicians

• Washing devices for each room • Clean material storage room

• Contaminated material storage room • Waiting room for patients’ family members • Room for meeting with patients’ family members

3.3.D. Clinic

I) Structural requirements21

The surface area should be at least 12 m2. The transplant clinic should have:

• A dedicated area for outpatient visit (surgeon/hepatologist) • An ultrasound area

• Area to store the charts • Reception area

II) Technological requirements

• Standard clinics devices (dressing devices, beds, desks, etc…) • Scale

• Ultrasound

• Computer for data collection

III) Organizational requirements

• Surgeon and internal medicine physician should be always available when scheduled

• A nurse must be available

3.4. Personnel requirements 3.4.A. Targets

The targets of this document are to provide:

• The minimum required supporting and verification documents;

• The minimum training and educational requirements for a transplant center personnel and others specialties involved, including (adapted from references

24,25,26):

o Transplant manager

o Liver transplant surgeon

o Hepatologist o Anesthesiologist o Transplant Coordinator o Transplant nurse o Immunologist o Laboratory personnel Transplant manager

MINIMUM REQUIRED CRITERIA:

1. On site

2. M.D. or R.N. or equivalent degree

42

1. Observe the evaluation of the donor and donor process, and management

of at least 15 multiple organ donors which include the liver;

2. Minimum of 10 liver patients followed for a minimum of three months from

the time of their transplant;

3. Experience with pre-, peri-, and post-operative patient care within the last 1

year

PEDIATRIC PATHWAY:

1. Training in a program serving pediatric patients;

2. Transplant program at which training takes place performs an average

of at least 10 liver transplants per year;

3. Involved with 5 or more pediatric liver transplant recipients;

4. Followed 5 patients a minimum of 12 months from the time of their

transplant;

5. Experience with pre-, peri-, and post-operative care of 5 pediatric liver

transplants;

6. Observed the evaluation of the donor and donor process and

management of at least 5 multiple organ donors.

REQUIRED SUPPORTING DOCUMENTS:

1. Current CV;

2. Letter from the Credentialing Committee of the applicant hospital stating that

the candidate meets all requirements to be in good standing. Please provide

an explanation of any status other than active/full;

3. Letter from the candidate detailing his/her commitment to the program; level

of involvement with substantive patient care; and summarizing their previous

transplant experience;

5. A letter from the training director verifying that the candidate has met the

requirements;

6. A log (organized by date) of the transplant patients followed;

7. Transplant Experience: A letter from the program director verifying that the

individual has met the primary physician requirements and is qualified to

serve as a manager in a transplant program.

AREAS OF INVOLVEMENT IN THIS PROGRAM:EXPERIENCE AND TRAINING DESCRIPTION

This position serves to establish, implement, develop and control best practices for

project management throughout the organization.

• The manager will create formal methodologies for defining project key performance metrics and allocating resources;

• Must be able to successfully complete established competencies for the position within designated probationary period;

• Performs all legal responsibilities according to hospital policies and procedures; • Oversees or directly supervises department staff, including orientation, training

and evaluation within established guidelines;

• Maintains a department staffing plan that meets organizational needs; • Assesses, develops, implements and evaluates department goals that coincide

with the hospital goals on a yearly basis;

• Demonstrates personal and professional growth and expertise by remaining current with state associations and with professional trends, and by participating

in community activities;

• Coordinates the departmental performance improvement process including the preparation, analysis, and submission of required reports;

44

• Establishes standards, provides training and enforces compliance of departmental hospital customer service program.

Liver transplant surgeon

MINIMUM REQUIRED CRITERIA

• On site;

• M.D. or equivalent and Certified by the national competent authority; • Two year liver transplant fellowship:

a. Primary surgeon or first assistant on at least 45 liver transplants;

b. Primary surgeon or first assistant on at least 20 liver procurements of which 3

include the selection of the donor;

c. Involved in all levels of pre-, peri-, and post-operative patient care within the

last 2 years.

PEDIATRIC PATHWAY

• Training in a Transplant Program that serves predominantly Pediatric Patients (minimum 10 cases/year)

• Primary surgeon or first assistant on at least 15 liver transplants in patients younger than 18

• First assistant on at least 2 split/living donor liver procedure

• Demonstrate that the individual has maintained current working knowledge in all aspects liver transplantation and patient care within the last 2 years.

REQUIRED SUPPORTING DOCUMENTS

• Letter from the Credentialing Committee of the applicant hospital stating that the surgeon meets all requirements to be in good standing. Please provide an

explanation of any status other than active/full;

• Letter from the Surgeon detailing his/her commitment to the program and describing their transplant experience/training;

• Formal Training:

o A letter from the training director verifying that the fellow has met the

requirements;

o A log (organized by date) of the transplant and procurement procedures

DESCRIBE LEVEL OF INVOLVEMENT AND EXPERIENCE/TRAINING

• Management of patients with end stage liver disease • Recipient selection

• Donor selection

• Histocompatibility and tissue typing • Transplant surgery

• Post-operative and continuing inpatient care • Use of immunosuppressive therapy

• Differential diagnosis of liver allograft dysfunction • Histologic interpretation of allograft biopsies • Interpretation of ancillary tests for liver dysfunction • Long-term outpatient care

• Coverage of multiple transplant centers (if applicable)

Hepatologist

MINIMUM REQUIRED CRITERIA

• On site

• M.D., or equivalent degree from another country

• Certified in Gastroenterology by the national competent authority • Direct involvement in liver transplant patient care within the last 2 years • Transplant Hepatology Fellowship:

46

o Involved in primary care of 20 or more liver transplant recipients for a

minimum of 3 months from the time of their transplant

o Observed the evaluation of at least 20 recipients

o Observed the evaluation of the donor and donor process and management of at least 3 multiple organ donors that include the liver

PEDIATRIC PATHWAY

• Pediatric Gastroenterology Fellowship:

o Training in a transplant program at which training takes place performs

an average of at least 10 liver transplants on pediatric patients per year;

o Involved in the primary care of 10 or more pediatric liver transplant

recipients;

o Followed 10 pediatric liver transplant recipients for a minimum of 3

months from the time of their transplant;

o Direct involvement in the pre-, peri-, and post-operative care of 10 or

more pediatric liver recipients;

o Observed the evaluation of the donor and the donor process and

management of at least 3 multiple pediatric organ donors that include

the liver.

REQUIRED SUPPORTING DOCUMENTS

• Current CV;

• Letter from the Credentialing Committee of the applicant hospital stating that the physician meets all requirements to be in good standing. Please provide an

explanation of any status other than active/full;

• Letter from the physician detailing his/her commitment to the program; level of involvement with substantive patient care, and summarizing their previous

transplant experience;

• Formal Training;

requirements;

o A log (organized by date) of the transplant patients followed;

o Transplant experience: A letter from the program director verifying that

the individual has met the primary physician requirements and is

qualified to direct a liver transplant program.

DESCRIBE LEVEL OF INVOLVEMENT AND TRAINING/EXPERIENCE

• Management of patients with end stage liver disease • Care of acute liver failure

• Recipient selection • Donor selection

• Histocompatibility and tissue typing

• Post-operative and continuing inpatient care • Use of immunosuppressive therapy

• Differential diagnosis of liver allograft dysfunction • Histologic interpretation of allograft biopsies • Interpretation of ancillary tests for liver dysfunction • Long term outpatient care

• Fluid and electrolyte management

• Effects of transplantation and immunosuppressive agents on growth and development

• Manifestation of rejection in the pediatric patient

Anesthesiologist

MINIMUM REQUIRED CRITERIA