title: Low-dose steroids associated with milder histological changes after pediatric liver transplantation.
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.
authors.affiliation: Pediatric Surgery and Pediatric Transplantation Surgery, Children's Hospital, University of Helsinki, Helsinki, Finland. silja.kosola@hus.fi
authors.forename: Silja
authors.initials: S
authors.lastname: Kosola
authors.forename: Hanna
authors.initials: H
authors.lastname: Lampela
authors.forename: Hannu
authors.initials: H
authors.lastname: Jalanko
authors.forename: Heikki
authors.initials: H
authors.lastname: Mäkisalo
authors.forename: Jouko
authors.initials: J
authors.lastname: Lohi
authors.forename: Johanna
authors.initials: J
authors.lastname: Arola
authors.forename: Mikko P
authors.initials: MP
authors.lastname: Pakarinen
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D002779:Cholestasis / Q000139:chemically induced / Q000473:pathology; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D005234:Fatty Liver / Q000139:chemically induced / Q000473:pathology; D005260:Female; D005387:Finland; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology / Q000601:surgery*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000473:pathology; D016031:Liver Transplantation / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D011237:Predictive Value of Tests; D013256:Steroids / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D013256:Steroids