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

Abstract

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 1year post-LT prior to stopping steroids, then at 5years and every 5years thereafter. Target tacrolimus levels are 5-8μg/L and 3-5μg/L after 3 and 12months, respectively. Between 2002 and 2009, 51 LT were performed; 50 (98%) and 49 (96%) patients survived for 1 and 5years, respectively. A total of 43 patients (median age at LT 2.3years) underwent a protocol biopsy at 1year (16 male; median time post-LT 12.5months), and 44 (20 male; median time post-LT 5.1years) at 5years. By 5years, 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 5years. At 1 and 5years, 29 of 43 (67.5%) and 31 of 44 (71%) biopsies were normal, respectively. Two of 44 had chronic allograft hepatitis at 5years. 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 5years, respectively. Other findings included predominantly biliary changes (6/43 & 3/44 at 1 and 5years, respectively). Tacrolimus levels at 5years were slightly higher than anticipated (median trough level 5.8μg/L). With an immunosuppressive regimen of tacrolimus and low-dose steroids for 1year followed by tacrolimus monotherapy thereafter, the majority of PLB were normal and no progressive changes were observed at 5years. Compared to other LT programs, we have lower rates of chronic allograft hepatitis, steatosis, and fibrosis at 5years. However, the tacrolimus levels at 5years 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.