Long-term outcomes after pediatric liver transplantation
Year: 2013
Type: dissertation
Study design: Observational Study
Abstract: Since survival rates after pediatric liver transplantation (LT) have improved, the focus of interest has shifted to gradually evolving histological changes, long-term complications, and quality of life. Histological changes and complications are closely associated with each other and the immunosuppressive medication used, and may in turn affect the LT recipient s perception of quality of life. This thesis investigates the survival and complication rates, usefulness of protocol liver biopsies and long-term histological status of the liver graft, and cholesterol metabolism profile after pediatric LT. The effect of immunosuppression on biopsy-proven changes and cholesterol metabolism is also evaluated. In the quality of life assessment, the effects of different complications are explored. The study population includes all 99 children less than 18 years who underwent LT in Finland between 1987 and 2007. Retrospective data on LT indications, surgical procedures, surgical and medical complications, immunosuppression, and annual follow-up visits were collected from patient records and the national LT registry. For 12 patients transplanted for hepatoblastoma (HB) or hepatocellular carcinoma (HCC), also relevant cancer treatment details were gathered. Cross-sectional data included liver biopsies of 54 LT recipients (82% of survivors), serum levels of noncholesterol sterols (surrogate markers of cholesterol metabolism) and fibroblast growth factor 21 (FGF21) in 49 LT recipients (74%), and health-related quality of life (HRQoL) assessment of 57 LT recipients (86%) at median 10-11 years posttransplant. Serum levels of noncholesterol sterols and FGF21 were compared to 93 controls matched for age and gender, and the HRQoL measurements to 141 randomly picked controls matched for age, gender, and place of residence. Of the 12 patients with liver malignancies, six had HB and six HCC. All patients received neoadjuvant chemotherapy, but no routine chemotherapy was administered after LT. Median time from diagnosis to LT was 7 (2-133) months. At LT, none of the patients had radiological evidence of extrahepatic disease. The overall survival rates at one, five, and ten years after LT were 100%, 80%, and 67%, respectively. Survival was similar between the tumor types, and two deaths occurred secondary to tumor recurrence, one of each type. Biopsies of 18 patients (33%) showed near-normal histology with minimal changes. Portal inflammation was present in 14 samples (26%), and was less frequent in patients whose immunosuppression included steroids (14% vs. 47%; p = 0.008). Fibrosis was found in 21 biopsies (39%), and fibrosis staging correlated negatively with serum prealbumin levels (r = -0.364, p = 0.007) and positively with portal inflammation (r = 0.350, p = 0.010) and periportal cytokeratin 7 staining (r = 0.529, p less than 0.001). Microvesicular steatosis was detected in 23 biopsies (43%; 5-80% of hepatocytes), and correlated with the patients body-mass-index (r = 0.458, p less than 0.001) but not with steroid use. The histological findings were mainly mild and led to treatment changes in ten patients (19%), while only one minor complication was encountered. Serum lipid levels were similar in LT recipients and controls. LT recipients, however, displayed increased whole-body synthesis and decreased absorption of cholesterol compared to controls (lathosterol to cholesterol ratio 129 ± 55 vs. 96 ± 41, respectively, p less than 0.001; campesterol to cholesterol ratio 233 ± 91 vs. 316 ± 107, respectively, p less than 0.001). Low-dose methylprednisolone and azathioprine were negatively associated with the lathosterol/sitosterol ratio (r = -0.492, p less than 0.001 and r = -0.383, p = 0.007, respectively) reflecting a favorable effect on cholesterol metabolism. FGF21 levels were higher in LT recipients than in controls (248 pg/mL vs. 77 pg/mL, p less than 0.001). Under school-aged LT recipients and controls had similar HRQoL, and 54% of LT recipients aged over 7 scored within the controls normal range on all HRQoL domains. Biliary complications, reoperations, and obesity were independently associated with decreased HRQoL (p less than 0.05 for all). For those LT recipients already attending adult health care, physical functioning and general health yielded reduced scores (p less than 0.05). Still 64% of adults considered their health excellent. Sexual health was similar to controls although LT recipients may experience problems with their orgasm strength (p = 0.050). In conclusion, continued use of low-dose steroids seems to be associated with milder changes of both liver graft histology and cholesterol metabolism. Normal HRQoL and sexual health are achievable in long-term survivors of pediatric LT.
Source: Työväentutkimus Vuosikirja
Author: Silja Kosola
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1923144436