Varma Sharat, Stéphenne Xavier, Komuta Mina, Bouzin Caroline, Ambroise Jerome, Smets Françoise, Reding Raymond, Sokal Etienne M
Service de Gastroentérologie et Hépatologie Pédiatrique, Université Catholique de Louvain, Cliniques Universitaires St Luc, Brussels, Belgium.
Pediatric Research Unit, Université Catholique de Louvain, Cliniques Universitaires St Luc, Brussels, Belgium.
Pediatr Transplant. 2017 Feb;21(1). doi: 10.1111/petr.12834. Epub 2016 Oct 23.
Activated hepatic stellate cells express cytoplasmic ASMA prior to secreting collagen and consequent liver fibrosis. We hypothesized that quantifying ASMA could predict severity of future fibrosis after LT. For this, 32 pairs of protocol biopsies, that is, "baseline" and "follow-up" biopsies taken at 1- to 2-year intervals from 18 stable pediatric LT recipients, transplanted between 2006 and 2012 were selected. Morphometric quantification of "ASMA-positive area percentage" was performed on the baseline biopsy. Histological and fibrosis assessment using Metavir and LAFSc was performed on all biopsies. The difference of fibrosis severity between the "baseline" and "follow-up" was termed "prospective change in fibrosis." Significant association was seen between extent of ASMA positivity on baseline biopsy and "prospective change in fibrosis" using Metavir (P=.02), cumulative LAFSc (P=.02), and portal LAFSc (P=.01) values. ASMA-positive area percentage >1.05 predicted increased fibrosis on next biopsy with 90.0% specificity. Additionally, an association was observed between extent of ASMA positivity and concomitant ductular reaction (P=.06), but not with histological inflammation in the portal tract or lobular area. Hence, ASMA quantification can predict the future course of fibrosis.
活化的肝星状细胞在分泌胶原蛋白及随后发生肝纤维化之前会表达细胞质平滑肌肌动蛋白(ASMA)。我们推测,对ASMA进行定量分析可以预测肝移植(LT)后未来纤维化的严重程度。为此,我们从2006年至2012年间接受移植的18名稳定的小儿肝移植受者中,选取了32对方案活检样本,即每隔1至2年采集的“基线”和“随访”活检样本。在基线活检样本上对“ASMA阳性面积百分比”进行形态计量学定量分析。对所有活检样本进行使用梅塔维尔(Metavir)和肝纤维化评分系统(LAFSc)的组织学和纤维化评估。“基线”和“随访”之间纤维化严重程度的差异被称为“纤维化的前瞻性变化”。使用梅塔维尔(Metavir)(P = 0.02)、累积肝纤维化评分系统(LAFSc)(P = 0.02)和门静脉肝纤维化评分系统(portal LAFSc)(P = 0.01)值,在基线活检样本上ASMA阳性程度与“纤维化的前瞻性变化”之间存在显著关联。ASMA阳性面积百分比>1.05预测下一次活检时纤维化增加,特异性为90.0%。此外,观察到ASMA阳性程度与伴随的小胆管反应之间存在关联(P = 0.06),但与门静脉或小叶区域的组织学炎症无关。因此,ASMA定量分析可以预测纤维化的未来进程。