Low-dose steroids associated with milder histological changes after pediatric liver transplantation

Liver Transpl. 2013 Feb;19(2):145-54. doi: 10.1002/lt.23565.

Abstract

Controversy remains about the role of protocol liver biopsy for symptom-free recipients and about the long-term use of low-dose steroids after pediatric liver transplantation (LT). We conducted a national cross-sectional study of pediatric recipients who underwent LT between 1987 and 2007. Liver biopsy samples were taken from 54 patients (82% of survivors) after a median posttransplant follow-up of 11 years, and they were reviewed by 2 pathologists blinded to the clinical data. Biopsy samples from 18 patients (33%) showed nearly normal histology with no inflammation, fibrosis, or steatosis. Portal inflammation was detected in 14 samples (26%), showed no correlation with anti-nuclear antibodies, and was less frequent in the 35 patients whose immunosuppression included steroids (14% versus 47% of patients not using steroids, P = 0.008). Fibrosis was present in 21 biopsy samples (39%). According to the Metavir classification, 16 were stage 1, 3 were stage 2, and 2 were stage 3. The fibrosis stage correlated negatively with serum prealbumin levels (r = -0.364, P = 0.007) and positively with chronic cholestasis (cytokeratin 7 staining; r = 0.529, P < 0.001) and portal inflammation (r = 0.350, P = 0.01). Microvesicular steatosis was found in 23 biopsy samples (43% of patients in 5%-80% of hepatocytes), and it correlated with the body mass index (r = 0.458, P < 0.001) but not with steroid use. The age of the allograft (donor age plus follow-up time) correlated with higher serum gamma-glutamyltransferase (r = 0.472, P < 0.001) and conjugated bilirubin levels (r = 0.420, P = 0.002) as well as chronic cholestasis (r = 0.299, P = 0.03). The biopsy findings led to treatment changes in 10 patients (19%), whereas only 1 complication (subcapsular hematoma) was encountered. In conclusion, continuing low-dose steroids indefinitely after pediatric LT may have a positive effect on the long-term histological state of the liver graft. Allograft aging may lead to chronic cholestasis and thus contribute to the development of liver fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Biomarkers / analysis
  • Biopsy
  • Chi-Square Distribution
  • Child
  • Child, Preschool
  • Cholestasis / chemically induced
  • Cholestasis / pathology
  • Cross-Sectional Studies
  • Dose-Response Relationship, Drug
  • Fatty Liver / chemically induced
  • Fatty Liver / pathology
  • Female
  • Finland
  • Graft Survival / drug effects*
  • Humans
  • Immunohistochemistry
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Liver / chemistry
  • Liver / drug effects*
  • Liver / pathology
  • Liver / surgery*
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / pathology
  • Liver Transplantation / adverse effects
  • Liver Transplantation / immunology*
  • Male
  • Predictive Value of Tests
  • Steroids / administration & dosage*
  • Steroids / adverse effects
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers
  • Immunosuppressive Agents
  • Steroids