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 lowdose 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 ¼ 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 ¼ À0.364, P ¼ 0.007) and positively with chronic cholestasis (cytokeratin 7 staining; r ¼ 0.546, P < 0.001) and portal inflammation (r ¼ 0.350, P ¼ 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 ¼ 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 ¼ 0.472, P < 0.001) and conjugated bilirubin levels (r ¼ 0.420, P ¼ 0.002) as well as chronic cholestasis (r ¼ 0.305, P ¼ 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. V C 2012 AASLD.Received July 17, 2012; accepted October 15, 2012.Because good long-term survival after pediatric liver transplantation (LT) may now be expected in the majority of patients, issues related to the persistence of stable liver function and preserved histology are becoming more relevant. Although liver biopsy is widely used in the early posttransplant period, controversy remains about whether the routine follow-up of symptom-free LT recipients should include liver

Metabolic syndrome after pediatric liver transplantation

“…In adult patients with NAFLD, the NAFLD fibrosis score, the AST/platelet ratio index, and the BARD score predicted liver‐related events, and the NAFLD fibrosis score also predicted death or LT . Among our patients, however, the AST/platelet ratio index was low (median = 0.42) and showed no connection to liver steatosis, and liver fibrosis was mainly METAVIR stage 1; this makes the proposed predictive systems inapplicable.…”

“…Five patients also had macrovesicular steatosis in up to 33% of hepatocytes. The greatest NAFLD activity score was 1 for all patients, and no cases of steatohepatitis were encountered …”

“…A cutoff value of 33% was used to differentiate between mild and moderate steatosis. The NAFLD activity score was calculated as the unweighted sum of the scores for steatosis (0‐3), lobular inflammation (0‐3), and ballooning (0‐2), with the total ranging from 0 to 8 as proposed by Kleiner et al Biopsy findings have been reported in detail previously . Alcohol consumption in patients older than 18 years was estimated to be scant on the basis of the Alcohol Use Disorders Identification Test questionnaire returned by 73% (30/41) of the adult patients.…”

Late hepatic artery thrombosis after pediatric liver transplantation: A cross-sectional study of 34 patients

“…Only a few cases of late HAT were present in a pediatric protocol liver biopsy study; therefore, putting our findings (although not significant) in context with other protocol liver biopsy studies remains open. A recent study from our center observed a correlation between GGT and chronic cholestasis, and this study (examining a subset of patients from ref. 11) also showed a correlation between GGT and chronic cholestasis.…”

“…Liver biopsy was performed as part of the routine clinical follow‐up protocol regardless of patient symptoms. A detailed description of the histological methods and the results of biopsy findings have been reported previously . Briefly, core needle biopsy was performed under ultrasound guidance, and biopsy specimens were fixed, embedded, and stained with conventional histochemical methods.…”