Posttransplant immune hepatitis in pediatric liver transplant recipients: Incidence and maintenance therapy with azathioprine

Background. Cases of so-called autoimmune hepatitis (AH) have been reported after liver transplantation. Our aim was to evaluate the incidence in a se ries of 471 pediatric liver transplant recipients. Methods. Between 1984 and 1998, 471 children had orthotopic liver transplan tation (OLT). Children are followed up on a regular basis, with full clinic al, biochemical, and histologic evaluation at 6 months, 1, 2, 5, 7, and 10 years after OLT. Children with unexplained abnormal liver tests were screen ed for autoimmune markers (total gamma-globulins, smooth muscle antibodies [SMA], liver kidney microsome antibodies [LKM], antinuclear factor [ANA]). From January of 1998 until December of 1998, autoimmune markers were prospe ctively searched in all children admitted for regular posttransplant follow -up (n = 118). Results. Eleven of 471 children (2.35%) were found with autoimmune hepatiti s, 9 retrospectively and 2 prospectively. None had previous autoimmune live r disease. Patients had a history of steroid-dependent hepatitis. Histology showed variable degree of portal and lobular inflammation, piecemeal necro sis, and bridging collapse. Mean (+/- SDS) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities at diagnosis were 173 +/- 14 5 and 196 +/- 157 IU/L, respectively (nl < 32). Median gamma-globulin level s reached 1365 mg/dl versus 931 mg/dl in controls (P <0.05). Nine had ANA ( titer 1/80 up to 1/10,000), 1 SMA (1/320), and 2 LKM1 antibodies (1/1280). Patients did not respond to increasing charge of cyclosporine (n=10) or tac rolimus (n=1). Eleven received steroids (prednisolone: 2 mg/kg per day, the n tapered) and azathioprine (1.5 to 2.5 mg/kg per day). All patients normal ized within 3 months (mean AST/ALT levels of 26 +/-8 and 30 +/-9 IU/L). Thr ee had mild to moderate relapse with increase of ALT thereafter. Gamma-glob ulins decreased to 1190 mg/dl (ns). Amongst the 116 remaining prospectively evaluated patients, 85 had normal evaluation, despite low titers of autoan tibodies in 15 (SMA less than or equal to1/40, ANA 1/80). Thirty-one patien ts had graft dysfunction, related to well-explained posttransplant causes, among which 7 had similar low levels of autoantibodies. Conclusions. A total of 2.35% of our transplant children present evidence o f immune hepatitis after transplantation. Patients do not respond to increa sing cyclosporine or tacrolimus levels and require steroid and azathioprine . In view of this specific treatment, systematic screening for "autoimmune" markers is advised in children with liver transplant.