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

Authors


  • This study was supported by Helsinki University Central Hospital (through a grant), the Finnish Pediatric Research Foundation, the Finnish Transplantation Society, the Sigrid Juselius Foundation, the Päivikki and Sakari Sohlberg Foundation, and the Academy of Finland.

Address reprint requests to Silja Kosola, M.D., Pediatric Surgery and Pediatric Transplantation Surgery, Children's Hospital, Helsinki University Central Hospital and University of Helsinki, Biomedicum 2C, Room 609, P.O. Box 705, FI-00029 Helsinki, Finland. Telephone: +358 50 544 4975. E-mail: silja.kosola@hus.fi

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 = 0.009). Fibrosis was present in 21 biopsy samples (39%). According to the Metavir classification, 15 were stage 1, 4 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 = 0.546, 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 = 0.517, 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 = 0.305, 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. Liver Transpl 19:145–154, 2013. © 2012 AASLD.

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