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

BACKGROUND: Liver allograft fibrosis (LAF) is prevalent among children with long-term survival after liver transplantation (LT). The authors aimed to identify clinical risk factors, with a focus on the impact of immunosuppression (IS) level in the early post-transplant period on LAF. METHODS: A retrospective study was conducted on pediatric LT recipients with at least 1-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, cytomegalovirus 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 IS during 1–3 years after LT seems crucial to ensure protection against LAF.