Department of Critical Liver Diseases, Liver Research Center.
Liver Transplantation Center, National Clinical Research Center for Digestive Diseases.
Int J Surg. 2023 Nov 1;109(11):3450-3458. doi: 10.1097/JS9.0000000000000631.
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.
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.
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).
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.
肝移植（LT）后长期存活的儿童中普遍存在肝移植纤维化（LAF）。作者旨在确定临床危险因素，重点关注移植后早期免疫抑制（IS）水平对 LAF 的影响。
对至少有 1 年随访的小儿 LT 受者进行回顾性研究。采用 Cox 回归模型分析与 LAF 相关的危险因素，并采用 landmark 分析评估 IS 水平对 LAF 的影响。对具有配对活检的患者进行纵向分析。
共纳入 139 例患者，共 174 例肝活检。随访时间为 2.3 至 5.9 年，91.4%的患者（7.9%为显著）检测到 LAF，其中 88.2%的患者肝功能正常。急性排斥反应、胆系并发症、巨细胞病毒感染和冷缺血时间延长是独立的危险因素。此外，术后 1-3、3-6、6-12 和 12-36 个月 IS 水平相对较低的患者发生 LAF 的风险较高。特别是术后 12-36 个月 IS 水平相对较高（平均他克莫司谷浓度≥5.1ng/ml）的患者，短期内发生 LAF 的风险降低 67%（P=0.006）。在配对分析中，IS 水平升高的患者更有可能实现纤维化减少（HR=7.53，P=0.025）。
小儿 LT 受者中普遍存在轻度至中度 LAF，且可能早期出现且无症状。LT 后 1-3 年内维持适当的 IS 水平对于防止 LAF 似乎至关重要。
