Paediatric Liver Transplant Programme

Wits Donald Gordon Medical

Centre

J Loveland, J Botha, R Britz, B Strobele, S Rambarran, A Terblanche , C Kock, P Walabh,

M Beretta, M Duncan et al

1817

1st clear English language reference to BA

Burns J. Principles of Midwifery, including the diseases of women and children 1817:602

John Burns Regius Professor of Surgery

University of Glasgow

“reveal the presence of”

“Looking at the problem of biliary atresia from the vantage point of 30 years’ experience with the

lesion, we can say with certainty that the jaundiced baby who has had no extrahepatic bile duct has

been the most disappointing patient for the surgeon in the whole realm of lesions theoretically

correctable by a surgical procedure.”

• Scientific fields progress in a linear and continuous way

• Laborious grind and dog work

• Predictable “solving of puzzles that are left open in a current field of

knowledge…..a pleasant way to keep busy when one is not up to useful work”

Grosfeld

Davenport

Coran Hind

Puri

Millar

Loveland

The Structure of Scientific Revolutions

“Normal science with a paradigm and a dedication to solving puzzles; followed by

serious anomalies, which lead to a crisis; and finally resolution of the crisis by a new

paradigm”

Paradigm shift in treatment and outcomes

Ian Hacking Introductory Essay “The Structure of Scientific Revolutions”

Kasai et al. Journal of Paediatric Surgery 1968 3 (6) 665 -675

• Alluded to ductal diameter of 150 microns as potentially prognostic for drainage

• 10 of 14 with ducts > 200μ drained • Only 1 of 13 < 150μ

“Size may be of great significance”

• All cured cases surgery before 4 months of age

Kasai et al. Journal of Paediatric Surgery 1968 3 (6) 665 -675

“Not a few cases …. Might be curable if portoenterostomy carried out before 4 months of

age, preferably within 3 months after birth”

The First

• 1963 C Henry Kempe presented Bennie Solis to Starzl

• Department of Paediatrics University of Colorado

• Infectious Diseases Specialist

• Coined term “Battered Child Syndrome”

• Defender of children

• Starzl suggested transplant – Kempe agreed • 1981 when moved to Pittsburgh, firmly supported moving

program forward

“The Puzzle People”

• Complementary role of KP and LT now accepted standard treatment BA

• Sequential employment significantly improved prognosis

Otte et al. Hepatology 1994 20(Suppl):41S-48S

Vacanti et al. Journal of Pediatric Surgery 1990 25:149 - 152

Loveland et al. S Afr Med J 2012;102(4):233-236

SO WHERE ARE WE TODAY…

• 134 transplants • 8 re-transplants

• 36.57% LDLT (49/134)

• 34.33% whole (46/134)

• 18.66% splits (25/134)

• 10.45% Reduced size (14/134)

• 12 fulminant hepatic failure

• 12 CLKT

UNIT GROWTH

0

5

10

15

20

25

30

20

05

20

06

20

07

20

08

20

09

20

10

20

11

20

12

20

13

20

14

20

15

20

16

20

17

(1

st 6

m)

Nu

mb

er

of

tran

spla

nts

Year of transplant

DEMOGRAPHIC OF AETIOLOGY

0 10 20 30 40 50 60

biliary atresia

budd chiari - veno-occlusive disease

oxalisis

auto-immune disease

chronic rejection of liver graft

alpha-1 antitrypsin deficiency

alagille syndrome (biliary hypoplasia)

wilson's disease

polycystic kidney disease and hepatic fibrosis

biliary agenesis

hepatoblastoma

hepatocellular carcinoma

cryptogenic

maple syrup urine disease

PFIC - progressive familial intrahepatic cholestasis

other

% of recpients with chronic liver failure (n=117)

IMMUNOSUPPRESSION

0

10

20

30

40

50

60

70

80

90

100

steroids tacrolimus MMF other

% o

f re

cip

ien

ts (

n=1

15

)

Immunosuppression at time of transplant

Entire Series

134

Era 1

31

Era 2 103

Whole Grafts

46

18 (58%)

28 (27.18%)

Reduced Size Grafts

14

10 (32%)

4 (3.88%)

Split Grafts

25

3 (10%)

22 (21.6%)

Living Donor Grafts

49

0

49 (47.57%)

GRAFT UTILIZATION

0 5 10 15 20 25 30

LDLT

Split

Reduced

Whole

Era 1: 2005 - 2012

Era 2: 2012 - Present

GRAFT TYPE BY ERA

Loveland et al. S Afr Med J 2014 104 (11) 799 - 802

RECIPIENT AGE

Entire Series

Era 1

Era 2

Age Range (months)

9 – 213

9 – 213

9 – 214

Mean Age

82.39

100.86

64.73

Median Age

50

101

45

Weight Range (kilograms)

5 – 62

5 – 62

6 – 45

Mean Weight

21

25.21

16.94

Median Weight

14.1

23

12.75

Loveland et al. S Afr Med J 2014 104 (11) 799 - 802

RECIPIENT WEIGHT

Entire Series

Era 1

Era 2

Age Range (months)

9 – 213

9 – 213

9 – 214

Mean Age

82.39

100.86

64.73

Median Age

50

101

45

Weight Range

(kilograms)

5 – 62

5 – 62

6 – 45

Mean Weight

21

25.21

16.94

Median Weight

14.1

23

12.75

Loveland et al. S Afr Med J 2014 104 (11) 799 - 802

0 1 2 3 4 50

10

20

30

40

50

60

70

80

90

100

Time

Perc

en

t su

rviv

al

Patient Survival

HEPATIC ARTERY THORMBOSIS

• 4.5% incidence (6/134)

• 1 Reduced = HAT Day 1 = Died before ReTx

• 1 Whole = ReTx = Died

• 1 Whole = Revised D1 = NAD

• 1 Whole = HAT Day 9 = ReTx Day 22 = NAD

• 1 Split = HAT Day 10 = ReTx Day 13 = Died

• 1 Whole = HAT Day 21 = Good function to date

• 1 Whole = Rupture D11 = Revised

VASCULAR COMPLICATIONS

• 7 PVT and 1 PVS

– 1 PVT revised with venous interposition

– 1 PVS required angioplasty and stent

– 1 PVT required splenorenal shunt

• Another planned

• 2 patients venoplasty caval anastomosis

BILIARY COMPLICATIONS

• Increased incidence after split and LDLT – Cut surface leaks

• Long term increase in strictures – Ischaemia

• Attention to detail: – LDLT harvest

– Back table split

– Biliary reconstruction during implant

– Meticulous arterial reconstruction

LARGE FOR SIZE SYNDROME

IMPACT OF LDLT

• Access greater organ pool – Significant ethical issues

• Benefits – Decreasing waiting list death – “elective” transplant – Well matched organ

• may lead to better long-term graft and patient survival

• Donor operation places well individual at risk:

– morbidity overall average 35%

• Decision made without coercion • Psychosocial evaluation • Anatomical assessment

OF SIGNIFICANCE….

THE IMPACT OF -3…..

0

10

20

30

40

50

60

70

80

90

100

Weight Height MUAC

% o

f p

atie

nts

age

d <

=5y

3

2

0

-1

-2

-3

ANOTHER SIGNIFICANT HAZARD

• 3.5 (95% CI 1.2-10) for patient survival

• 3.2 (95% CI 1.2-8.4) for liver graft survival

NOSOCOMIAL INFECTION

76.3%

16.6%

7.1%

Bacterial Viral Fungal / yeast

0

50

100

150

200

250

Nu

mb

er

of in

fectio

ns

INTERVENTION – BILIARY ATRESIA

• Identification

• Early referral • Surgery

• Centralization

• Follow up

• Early referral • Transplant assessment

INTERVENTION – TRANSPLANT • Nutritional support

• Pre-transplant

• Infection control

• Venous access and care

• Antibiotic stewardship

• Long Term outcomes • Immunosuppression