New Onset “Autoimmune Hepatitis“ in Liver Pediatric Recipients.

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Presentation transcript:

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 long- term complication of pediatric OLT and links with other post-operative diseases

MATERIALS median age at tx 1.8 yrs. ( yrs.) median follow-up 1.5 yrs. ( yrs.) 113 liver tx in 102 pts

NATIVE DISEASES

IMMUNOSUPPRESSION  CYCLOSPORIN 58  TACROLIMUS 29  SWITCH CYCLO - TACRO 15

OLT & AUTOANTIBODIES 16 / 102 pts ( 15 % ) median age at tx 3.7 yrs ( yrs.) median follow-up 1.5 yrs. ( yrs.) median time from OLT 3.6 yrs ( yrs.)

TYPE OF GRAFT 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 ANA + ASMA 5 ANA 4 ASMA 1 ASMA+ ANA + ENA 1 ASMA + cANCA 2 LKM

CLINICAL PRESENTATION  median ALT 145 U./l. (n.v. up to 45 U./l. ) range  median IgG 1400 mg. / dl. ( n.v mg./ dl. ) range

AUTOIMMUNE HEPATITIS SCORE * * J. Hepatology 31: , 1999

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)

CLINICAL FOLLOW - UP CLINICAL FOLLOW - UP NO THERAPY 10 PERSISTENCE OF AUTOAB’S 7 DISAPPAEARANCE OF AUTOAB’S 3 STEROIDS THERAPY 2 PERSISTENCE OF AUTOAB’S 2 STEROIDS & AZOTHIOPRINE 4 PERSISTENCE OF AUTOAB’S 4

HISTOLOGICAL FOLLOW-UP NO THERAPY 1 1 UNCHANGED STEROIDS & AZOTHIOPRINE 4 2 UNCHANGED * 2 IMPROVED 1 ( 4 TO 2 HAI ) 1 ( 5 TO 2 HAI ) * 1 pt. w/autoab’s disapparearance

EBV - STATUS 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/OUT AUTOAB 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 NO AUTOAB AUTOAB

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 ?