The long-term histological outcome after pediatric
liver transplantation (OLT) is not yet fully understood. De novo
autoimmune hepatitis, consisting of histological
chronic hepatitis associated with
autoantibody formation and allograft dysfunction, is increasingly recognized as an important complication of
liver transplantation, particularly in the pediatric population. In this study, 158 asymptomatic children with 5-year graft survival underwent protocol liver biopsies (113, 135, and 64 at 1, 5, and 10 years after OLT, respectively). Histological changes we re correlated with dinical,biochemical, and serological findings. All patients received cydosporine A as primary immunosuppression with withdrawal of
corticosteroids at 3 months post OLT. Normal or near-normal histology was reported in 77 of 113 (68%), 61 of 135 (45%), and 20 of 64 (31%) at 1, 5, and 10 years, respectively. The commonest histological abnormality was
chronic hepatitis (CH), the incidence of which increased with time [25/113 (22%), 58/135 (43%), and 41/64 (64%) at 1, 5, and 10 years, respectively) (P < .0001)]. The incidence of
fibrosis associatedwith CH increasedwith time [13/25 (52%), 47/58 (81%), and 37/41 (91%) at 1, 5, and 10 years, respectively) (P < .0001)]. The severity of
fibrosis associated with CH also increased with time, such that by 10 years 15% had progressed to
cirrhosis.
Aspartate aminotransfemse (AST) levels were slightly elevated in children with CH (median levels 52 IU/L, 63 IU/L, and 48 IU/L at 1, 5, and 10 years, respectively), but this did not reach statistical significance compared with those with normal histology. On multivariate analysis, the only factor predictive of
chronic hepatitis was
autoantibody positivity (present in 13% and 10% of children with normal biopsies at 5 and 10 years, respectively, and 72% and 80% of those with CH at 5 and 10 years, respectively) (P < .0001). Four children with CH and
autoantibodies, who also had raised
immunoglobulin G (
IgG) levels and AST greater than 1.5 x normal fulfilled the diagnostic criteria for de novo
autoimmune hepatitis (AIH). Another two were found to be
hepatitis C positive. No definite cause for CH could be identified in the other cases. In condusion,
chronic hepatitis is a common finding in children after
liver transplantation and is associated with a high risk of developing progressive
fibrosis, leading to
cirrhosis. Standard liver biochemical tests cannot be relied on either in the diagnosis or in the monitoring of progress of chronic allograft
hepatitis. In contrast, the presence ofautoantibodies is strongly associated with the presence of CH. The cause of
chronic hepatitis in transplanted allografts is uncertain but may be immune mediated, representing a hepatitic form of chronic rejection.