The impact of immunosuppression level on liver allograft fibrosis after pediatric liver transplantation
Yi-Zhou Jiang1,2,3, Xin-Yan Zhao4, Guang-Peng Zhou2,3, Lin Wei2,3, Wei Qu2,3, Zhi-Gui Zeng2,3, Shan-Shan Wu5, Hai-Ming Zhang2,3, Ying Liu1,2,3, Yu-Le Tan2,3, Jun Wang2,3, Zhi-Jun Zhu2,3, Li-Ying Sun1,2,3.
1Department of Critical Liver Diseases, Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China; 2Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China; 3Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, People's Republic of China; 4Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China; 5Clinical Epidemiology and EBM Unit, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China
Introduction Liver allograft fibrosis (LAF) is prevalent among children with long-term survival after liver transplantation (LT). We aimed to identify clinical risk factors, with a focus on the impact of immunosuppression (IS) level in the early posttransplant period on LAF.
Methods A retrospective study on pediatric LT recipients with at least one-year follow up was conducted. Cox regression models were used to analyze risk factors associated with LAF, and landmark analysis was used to evaluate the impact of IS level on LAF. Longitudinal analysis was also conducted in patients with paired biopsies.
Results A total of 139 patients involving 174 liver biopsies were included. With 1.0 to 5.9 years of follow-up, LAF was detected in 91.4% of patients (9.4%-severe), up to 88.2% of whom showed normal liver function. Episodes of acute rejection, biliary complications, CMV infection and prolonged cold ischemia time were independent risk factors. Besides, the risk of LAF in patients with relatively low IS level at postoperative 1-3, 3-6, 6-12 and 12-36 months was higher than the counterparts. Especially, in patients with relatively high IS level (mean tacrolimus trough concentration ≥ 5.1ng/mL) during postoperative 12-36 months, the risk of LAF was 67% lower in short future (P = 0.006).
In paired analysis, patients with increasing TAC level were more likely to achieve fibrosis reduction (HR = 7.53, P = 0.025).
Conclusions Mild to moderate LAF is common among pediatric LT recipients and can appear early and silently. Maintaining adequate levels of immunosuppression during early posttransplant period seems crucial to ensure protection against LAF.
We thank doctor En-Hui He and Zhan-Xiong Yi for percutaneous ultrasound-guided liver biopsy for the patients.
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