Il trapianto di fegato e di intestino
in pediatria
Lorenzo D’Antiga. Bergamo - Italy 29 Nov 2014
Il trapianto di fegato
11/28/2014
2
Outline
Indications to OLT in children
Early complications
Late complications
Long-term outcome and
perspective
0
8
17
25
33
42
50
Age at presentation (years)
Pe
rce
nta
ge
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Frequency of liver disease according to
age at presentation (3700 pts, KCH – London)
Most cases present early in life
As reflected by Panel A, the activity of many cytochrome P-450 (CYP) isoforms and a single glucuronosyltransferase (UGT) isoform is markedly
diminished during the first two months of life. In addition, the acquisition of adult activity over time is enzyme- and isoform-specific.
(NEJM 2003;349:1157-1167)
Pediatric Liver Transplantation in Bergamo
(600 transplants). Age distribution
0
10
20
30
40
50
Num
ber
of
patients
0-1
1-2
2-3
3-4
4-5
5-6
6-7
7-8
8-9
9-10
10-1
1
11-1
2
12-1
3
13-1
4
14-1
5
15-1
6
16-1
7
17-1
8
18-1
9
19-2
0
20-2
1
Age at transplantation (years)
60%
Median age at OLT: 1.4 years
Indications to OLT in Bergamo
(600 pts)
EHBA
55% Inherited cholestatic
21%
Metabolic
9%
Fulminant
5%
Re-OLT
4%
Miscellaneous
6%
The split technique
Immunosuppressive drugs
Steroids
calcineurin inhibitors (CyA, Tacrolimus)
azathioprine
mycophenolate mofetil
mTOR inhibitors (sirolimus, everolimus)
anti IL2 receptor (basiliximab)
Outline
Indications to OLT in children
Early complications
Late complications
Long-term outcome and
perspective
Early complications
Bowel perforation
hepatic artery thrombosis
portal vein stenosis/thrombosis
biliary leak/strictures
outflow problems
acute cellular rejection
infection (CMV, EBV, bacterial)
renal impairment
Post transplant
lymphoproliferative disease
(PTLD)
surgical medical
Acute (cellular) rejection
2
3
1) Portal lymphocytic infiltrate
2) endothelitis
3) bile duct damage
1
Complications: hepatic-caval stenosis
5 year-old boy with Alagille Sdr. OLT
A few months after OLT large ascitis, graft dysfunction,
subcutaneous large vessels at lower abdomen
Caval stricture
Outline
Indications to OLT in children
Early complications
Late complications
Long-term outcome and
perspective
Complications related to immunosuppression
Late cellular rejection/chronic rejection
PTLD
infection (CMV, Varicella, influenza, Adenovirus, EBV, HPV,
bacterial)
Renal impairment/failure
de novo autoimmune hepatitis, chronic hepatitis
Bone disease
Dyslipidemia, diabetes, allergies
Hypertrophic cardiomyopathy
Hypertension
De novo malignancies
Post-transplant lymphoproliferative
disease (PTLD)
Affects 5-20% of all paediatric OLT
If EBV negative pre OLT => strict surveillance
Often preceded by sustained viral detection.
Non-specific symptoms : fever, malaise, mononucleosis-like, organ
enlargement gastrointestinal bleeding/anaemia,
High index of suspicion. Monitor EBV-DNA, pre-emptive approach.
imaging studies (USS, CT) are very important to detect the disease
mandatory to obtain tissue biopsies for final diagnosis
D’Antiga L et Al.: Liver Transplantation 2007;13:343-348
Hepatic osteodystrophy
short term long term
D’Antiga L et Al.: Transplantation 2002 D’Antiga L et Al.: Transplantation 2004
months
Skin cancer
Confirmed association with development of basal cell
and squamous cell carcinoma
Possible association with development of melanoma
Avoid exposure to sunlight, skin barriers not sufficient
to protect
Belloni-Fortina et Al. Arch Dermatol 2004; 140: 1079–1085.
Buell JF, Seminars in Pediatric Surgery, 2006;15:179
De novo tumours: incidence
Chronic kidney disease
Main cause: CNI
nephrotoxicity
Predisposing factors: older
age at OLT, reduced GFR at
OLT, underlying diagnosis
(Alagille, tyrosinemia,
polycistic kidney dis)
Arora-Gupta N, Pediatr Transplantation 2004
Outline
Indications to OLT in children
Early complications
Late complications
Long-term outcome and
perspective
Survival in ELTR database 01/1988 - 12/2010
Patient
ELTR registry
85%
Survival in Bergamo 01/1998 - 12/2013
92%
10-years survival (454 pts) 5-years survival (109 pts)
Chronic liver
disease in the
years 1970-1980:
60% mortality
Chronic liver
disease in the
years 2000-…:
90% survival
Il trapianto di intestino
Conditions leading to Intestinal Transplantation
(Pediatric)
Intestinal transplantation: different composite graft Definitions:
SBT intestine, but no liver or stomach
Liver/SBT intestine + liver, but no stomach
MVT intestine + stomach (± liver, ± spleen)
Fishbein T. N Engl J Med 2009;361:998-1008
David Sachs, Transplant Immunologist
“Transplanting the bowel? It’s
crazy: It is like transplanting a
huge lymph node enwrapped
in faeces”
Old (A and B) and new (C and D) views of transplantation recipients
Starzl T. E. PNAS 2004;101:14607-14614 Copyright © 2004, The National Academy of Sciences
Rejection
Consequences of transplanted donor lymphoid tissue
GVHD
Patient survival
32
What about graft function? 33
60% 50%
What is the best tolerated graft composition? 34
I risultati di Bergamo 35
Follow up medio: 1,7 anni
Sopravvivenza: 7/8 (87%)
Organi funzionanti: 6/9 (66%)
Nome
Data
Trapianto Tipo trapianto
Ultimo
f/up
Stato
Paziente Stato Organo
Data
Fallimento Durata f/up
GL 11/10/2006 FEGATO - INTESTINO 10/10/2007 Morto Funzionante 364
SC 14/06/2008 INTESTINO 02/05/2009 Vivo Funzionante 322
MMF 08/11/2008 INTESTINO 22/10/2011 Vivo Non Funzionante 13/01/2010 1078
FE 15/05/2009 MULTIVISCERALE 19/01/2012 Vivo Funzionante 979
VA 28/07/2009 MULTIVISCERALE 17/01/2012 Vivo Funzionante 903
TB 14/10/2009 FEGATO - INTESTINO 22/10/2011 Vivo Funzionante 738
FL 03/03/2010 MULTIVISCERALE MODIFICATO 07/11/2011 Vivo Funzionante 614
MMF 09/04/2010 INTESTINO 22/10/2011 Vivo Non Funzionante 10/10/2010 561
MG 21/08/2011 MULTIVISCERALE 19/01/2012 Vivo Funzionante 151
634
Complicanze gravi (PTLD, GVHD, PLE, rigetto cronico,
infezioni recidivanti): 7/9 (77%)
When to refer a child for ITx?
Intestinal failure itself is NOT an indication
Total AND definitive intestinal failure AND
complications of home PN
Indication is the impossibility to nourish the
patient by ant mean (NUTRITIONAL FAILURE)
D’Antiga & Goulet JPGN 2013
Survival: PN versus ITx
Pironi. Gut 2011;60:17-25
IT
X
Complicated
HPN
HPN
Complications that indicate ITx ?
Home PN impossible
Extensive vascular thrombosis. Loss of
venous access
Recurrent catheter infections
Severe liver disease
GRAZIE
Lorenzo D’Antiga Bergamo - Italy
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