Download MINIMAL CHANGES CHOLANGIOPATHY

New Onset
“Autoimmune Hepatitis“
in Liver Pediatric
Recipients
A. SONZOGNI , M. SPADA , S. RIVA,
M. COLLEDAN , A. LUCIANETTI,
A. SEGALIN, A. BERTANI, M. L. MELZI ,
B. GRIDELLI
LIVER TRANSPLANTATION CENTER,
OSPEDALI RIUNITI , BERGAMO , ITALY
A. J. DEMETRIS
TRANSPLANTATION PATHOLOGY UPMC,
PITTSBURGH PA , USA
M. MINERVINI
ISMETT , PALERMO , ITALY
INTRODUCTION
- de novo “autoimmune” hepatitis is
a major problem in pediatric
liver transplantation
- appearance of autoantibodies is
associated with a wide spectrum of
clinical / histological features
AIM OF THE STUDY
To investigate the impact of
“autoimmune hepatitis” as longterm complication of pediatric OLT
and links with other post-operative
diseases
MATERIALS
113 liver tx in 102 pts
• median age at tx 1.8 yrs. (0.2-17 yrs.)
• median follow-up 1.5 yrs. (0.2 - 10 yrs.)
NATIVE DISEASES
58%
alagille
biliary atresia
7%
pfic
fulminant hepatitis
hepatoblastoma
24%
5%
2% 4%
others
IMMUNOSUPPRESSION
CYCLOSPORIN
58
TACROLIMUS
29
SWITCH CYCLO - TACRO
15
OLT & AUTOANTIBODIES
16 / 102 pts ( 15 % )
• median age at tx 3.7 yrs ( 0.7 -15 yrs.)
• median follow-up 1.5 yrs. ( 0.4 - 10 yrs.)
• median time from OLT 3.6 yrs (0.2-9.9yrs.)
88%
biliary atresia
alagille
alfa- 1-deficiency
6%
6%
TYPE OF GRAFT
 WHOLE LIVER
7
 REDUCED LIVER II-III SEG.
4
 IN SITU SPLIT II-III SEGM.
5
IMMUNOSUPPRESSION IN
PTS. W/AUTOANTIBODIES
CYCLOSPORIN
8
TACROLIMUS
3
SWITCH CYCLO-TACROLIMUS
5
TYPE OF AUTOANTIBODIES
3
5
4
1
1
2
ANA + ASMA
ANA
ASMA
ASMA+ ANA + ENA
ASMA + cANCA
LKM
CLINICAL PRESENTATION
 median ALT
145 U./l.
(n.v. up to 45 U./l. )
range 45 - 350
 median IgG 1400 mg. / dl.
( n.v. 310 - 160 mg./ dl. )
range 600 - 2170
AUTOIMMUNE
HEPATITIS
SCORE *
* J. Hepatology 31: 929-938, 1999
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
7
1
1
5
11
9
10
7
5
6
-2
4
4
10
10
4
CLINICAL PRESENTATION
IN 7 / 16 PATIENTS LIVER
FUNCTION TEST ALTERATIONS
PRECEEDED APPEARANCE OF
AUTOANTIBODIES
MEDIUM LAG TIME 5.5 MONTHS
( 3-10 MONTHS)
PREVIOUS POST-OLT
COMPLICATIONS
 ACR ( 4 )
 biliary strictures ( 1 )
 ACR & polisierositis ( 1 )
 ACR & biliary strictures ( 2 )
 ACR & colic stricture ( 1 )
 ACR and portal thrombosis ( 1 )
 chronic varicella virus infection (1)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
chronic hepatitis HAI 4/18
chronic hepatitis HAI 3/18
chronic hepatitis HAI 3/18
chronic hepatitis HAI 5/18
chronic hepatitis HAI 4/18
chronic hepatitis HAI 4/18
chronic hepatitis HAI 3/18
chronic hepatitis HAI 9/18
chronic hepatitis HAI 4/18
biopsy not performed
ACR RAI 3/9; marginal bx
chronic hepatitis HAI 3/18
ACR RAI 4/9 + centr. venulitis
chronic hepatitis HAI 4/18
chronic hepatitis HAI 5/18
chronic hepatitis HAI 5/18
bridging fibrosis
indeterminate for ACR
fibr. stage 3;ACR RAI 5/9
marked steatosis
ACR RAI 5/9
bridging fibr.;ACR RAI 4/9
central necrosis,ACR indet.
coesistent chr. hepatitis?
ACR RAI 3/9
CLINICAL FOLLOW - UP
NO THERAPY
PERSISTENCE OF AUTOAB’S
DISAPPAEARANCE OF AUTOAB’S
STEROIDS THERAPY
PERSISTENCE OF AUTOAB’S
10
7
3
2
2
STEROIDS & AZOTHIOPRINE
PERSISTENCE OF AUTOAB’S
4
4
HISTOLOGICAL FOLLOW-UP
NO THERAPY
1
1 UNCHANGED
STEROIDS & AZOTHIOPRINE
2 UNCHANGED *
2 IMPROVED 1 ( 4 TO 2 HAI )
1 ( 5 TO 2 HAI )
* 1 pt. w/autoab’s disapparearance
4
EBV - STATUS
PTS W/OUT AUTOAB
•unknown EBV status 9
•follow-up <1 month
9
•medium follow-up 1.5 yrs
•known EBV status 68
EBNA-Ig +ve 32 (47 %)
EBNA-Ig -ve
36 (53 %)
PTS W/AUTOAB
•unknown EBV status 3
•medium follow-up
3 yrs
•known EBV status 13
EBNA-Ig +ve 3 (23 %)
EBNA-Ig -ve
10 (77 %)
EBV INFECTION POST - OLT
NO AUTOAB
9%
AUTOAB
31%
32%
no symptoms
EBV-DNA -ve
no symptoms
EBV-NA +ve
59%
38%
31%
symptomatic
EBV-DNA +ve
ITEMS TO BE FURTHER
INVESTIGATED



What is incidence of the disease ?
What is its outcome ?
Which is its treatment ?
ITEMS TO BE FURTHER
INVESTIGATED
•
Are there any links with
post-OLT infectious diseases ?
•
Are there any links with
native pathology ?