Histological findings in protocol biopsies following pediatric liver transplant: Low incidence of abnormalities at 5 years.

Histological abnormalities, including chronic hepatitis, fibrosis, and steatosis, are increasingly reported in liver biopsies of children after LT. These changes may be progressive and represent a form of rejection. Liver biochemistry is often initially normal. Our LT program began in 2002, utilizing tacrolimus and low-dose steroids for the first year post-LT. Patients undergo a protocol biopsy at 1 year post-LT prior to stopping steroids, then at 5 years and every 5 years thereafter. Target tacrolimus levels are 5-8 μg/L and 3-5 μg/L after 3 and 12 months, respectively. Between 2002 and 2009, 51 LT were performed; 50 (98%) and 49 (96%) patients survived for 1 and 5 years, respectively. A total of 43 patients (median age at LT 2.3 years) underwent a protocol biopsy at 1 year (16 male; median time post-LT 12.5 months), and 44 (20 male; median time post-LT 5.1 years) at 5 years. By 5 years, 3 had transferred to adult services; 1 was re-transplanted for graft failure and 1 moved overseas. Biopsies were reviewed by 2 pathologists. Most patients (31/44) were on tacrolimus monotherapy at 5 years. At 1 and 5 years, 29 of 43 (67.5%) and 31 of 44 (71%) biopsies were normal, respectively. Two of 44 had chronic allograft hepatitis at 5 years. Two of 43 and 1 of 44 had isolated fibrosis, 3 of 43 and 3 of 44 steatosis, and 3 of 43 and 4 of 44 acute rejection at 1 and 5 years, respectively. Other findings included predominantly biliary changes (6/43 & 3/44 at 1 and 5 years, respectively). Tacrolimus levels at 5 years were slightly higher than anticipated (median trough level 5.8 μg/L). With an immunosuppressive regimen of tacrolimus and low-dose steroids for 1 year followed by tacrolimus monotherapy thereafter, the majority of PLB were normal and no progressive changes were observed at 5 years. Compared to other LT programs, we have lower rates of chronic allograft hepatitis, steatosis, and fibrosis at 5 years. However, the tacrolimus levels at 5 years were higher than planned and this may have played a role. Further evaluation is also required to determine the potential long-term adverse effects of corticosteroid use on linear growth and bone mineral density.