Division of Abdominal Transplantation and Hepatobiliopancreatic SurgeryBambino Gesù Children's Hospital Istituto di Ricerca e di Cura a Carattere ScientificoRomeItaly.
Department of Surgical SciencesHepatopancreatobiliary and Transplant UnitUniversity of Rome Tor VergataRomeItaly.
Liver Transpl. 2022 Feb;28(2):280-293. doi: 10.1002/lt.26218. Epub 2021 Jul 31.
Allograft fibrosis (AF) after pediatric liver transplantation (pLT) is frequent, but its dynamics are unclear. Our aim was to assess the evolution and risk factors of AF after pLT. A retrospective single-center analysis of pLT patients with a follow-up of ≥5 years who underwent protocol liver biopsies at 6 months, 1 year, 2 years, 5 years, and 10 years was performed. Fibrosis was assessed using the METAVIR and Ishak systems and the liver allograft fibrosis score (LAFs). Of 219 pLTs performed from 2008 to 2018, 80 (36.5%) pLTs were included, and 320 biopsies were reviewed. At 6 months after pLT, fibrosis was found in 54 (67.5%) patients by the METAVIR/Ishak systems and in 59 (73.8%) by the LAFs (P = 0.65). By 5 years, AF was detected in 67 (83.8%), 69 (86.3%), and 72 (90%) specimens using the METAVIR, Ishak, and LAFs systems, respectively (P = 0.54); mild (METAVIR, 51 [63.8%]; Ishak, 60 [75%]; LAFs, 65 [81.2%]) and moderate (METAVIR, 16 [20%]; Ishak, 9 [11.9%]; LAFs, 7 [8.8%]) stages were detected, but severe fibrosis was not found (P = 0.09). In the LAFs, fibrosis involved the portal (85%), sinusoidal (15%), and centrolobular (12%) areas. Of 18 patients with 10-year protocol biopsies, AF was present in 16 (90%), including 1 (5.5%) with severe fibrosis. In all systems, 36.3% of patients showed fibrosis progression from 2 years to 5 years after LT, but they remained stable at the 10-year biopsies without clinical implications. In multivariate analysis, only donor age >40 years was a risk factor for moderate AF at 5 years after LT (odds ratio, 8.3; 95% confidence interval, 1.6-42.1, P = 0.01). Cold ischemia time (CIT) >8 hours was associated with portal (P < 0.001)/sinusoidal fibrosis (P = 0.04), donor age >40 years was associated with sinusoidal (P = 0.01)/centrilobular (P = 0.04) fibrosis, and low tacrolimus trough level within 1 year after LT was associated with centrilobular fibrosis (P = 0.02). AF has a high incidence after pLT, occurring early after transplantation. In most cases, AF is mild or moderate and remains stable in the long run without clinical implications. Donor selection, short CIT, and immunosuppression adherence are crucial to reducing the risk of advanced AF.
儿童肝移植（pLT）后同种异体纤维化（AF）很常见，但其动态变化尚不清楚。我们的目的是评估 pLT 后 AF 的演变和危险因素。对 2008 年至 2018 年间接受了方案性肝脏活检（6 个月、1 年、2 年、5 年和 10 年）且随访时间≥5 年的接受 pLT 的患者进行了回顾性单中心分析。使用 METAVIR 和 Ishak 系统以及肝移植纤维化评分（LAFs）评估纤维化。在 219 例接受 pLT 的患者中，有 80 例（36.5%）符合纳入标准，共回顾了 320 例活检。pLT 后 6 个月，METAVIR/Ishak 系统发现 54 例（67.5%）患者存在纤维化，LAFs 发现 59 例（73.8%）患者存在纤维化（P=0.65）。在 5 年时，分别有 67 例（83.8%）、69 例（86.3%）和 72 例（90%）标本通过 METAVIR、Ishak 和 LAFs 系统检测到 AF，差异无统计学意义（P=0.54）；轻度（METAVIR，51 例[63.8%]；Ishak，60 例[75%]；LAFs，65 例[81.2%]）和中度（METAVIR，16 例[20%]；Ishak，9 例[11.9%]；LAFs，7 例[8.8%]）纤维化阶段被发现，但未发现严重纤维化（P=0.09）。在 LAFs 中，纤维化累及门脉（85%）、窦状隙（15%）和中央静脉（12%）区域。18 例患者接受了 10 年的方案性活检，其中 16 例（90%）存在 AF，包括 1 例（5.5%）为严重纤维化。在所有系统中，36.3%的患者在 LT 后 2 年至 5 年期间出现纤维化进展，但在 10 年活检时纤维化保持稳定，无临床意义。多因素分析显示，只有供体年龄>40 岁是 LT 后 5 年发生中度 AF 的危险因素（比值比，8.3；95%置信区间，1.6-42.1，P=0.01）。冷缺血时间（CIT）>8 小时与门脉纤维化（P<0.001）/窦状隙纤维化（P=0.04）相关，供体年龄>40 岁与窦状隙纤维化（P=0.01）/中央静脉纤维化（P=0.04）相关，LT 后 1 年内他克莫司谷浓度低与中央静脉纤维化相关（P=0.02）。pLT 后 AF 的发病率较高，在移植后早期发生。在大多数情况下，AF 为轻度或中度，长期保持稳定，无临床意义。供体选择、短 CIT 和免疫抑制药物的依从性是降低进展性 AF 风险的关键。
