Impact of immunosuppression level on liver allograft fibrosis after pediatric liver transplantation: a retrospective cohort study

Abstract

Background: 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 was conducted on pediatric LT recipients with at least one year of follow-up. 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 2.3 to 5.9 years of follow-up, LAF was detected in 91.4% of patients (7.9% were significant), 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 levels at postoperative 1-3, 3-6, 6-12, and 12-36 months was higher than the counterparts. Especially, in patients with relatively high IS levels (mean tacrolimus trough concentration ≥5.1 ng/mL) during postoperative 12-36 months, the risk of LAF was 67% lower in the short future (P=0.006). In paired analysis, patients with increased IS levels 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 1 to 3 years after LT seems crucial to ensure protection against LAF.

Maintaining the optimum level of immunosuppressive agents minimizes risk of liver allograft fibrosis during Pediatric liver transplantation

“…A very recent study by Jiang et al . 1 conducted a retrospective cohort study to examine the effect of immunosuppressive level on liver allograft fibrosis (LAF) after liver transplantation in children and showed even in children with adequate liver function, a histologically proven mild to moderate LAF was very common, and its severity tended to worsen over time. In their finding, they also reported following liver transplantation, the immunosuppressive regimen should be modified over time based on the clinical condition of the patients.…”

“…Progressive LAF invariably causes graft failure and loss when left untreated 2 . LAF is one of the key elements influencing children’s long-term graft survival following liver transplantation in children 1 . Pediatric liver transplantation (PLT) is a lifesaving surgical intervention to manage acute, chronic, and end stages of liver disease, and it is considered the best treatment option when all types of medical treatments fail to cure liver diseases 3 , 4 .…”