Department of Pediatric Hepatology, Gastroenterology, and Nutrition, National Liver Institute, Menoufia University, 32511 Shebin El-koom, Menoufia, Egypt.
Department of Pathology, National Liver Institute, Menoufia University, 32511 Shebin El-koom, Menoufia, Egypt.
Hepatobiliary Pancreat Dis Int. 2021 Apr;20(2):154-162. doi: 10.1016/j.hbpd.2020.12.007. Epub 2020 Dec 9.
Liver fibrosis is a hallmark determinant of morbidity in biliary atresia (BA) even in successfully operated cases. Responsible factors for this rapid progression of fibrosis are not completely defined. Aberrant expression of the transcription factor SOX9 and hepatic progenitor cells (HPCs) proliferation have roles in fibrogenesis in cholestatic disorders. However, they were not investigated sufficiently in BA. We aimed to delineate the relation of SOX9 and HPCs to fibrosis and its progression in BA.
Forty-eight patients with BA who underwent an initial diagnostic liver biopsy (LB) and consequent intraoperative LB were recruited and compared to 28 cases with non-BA cholestasis that had an LB in their diagnostic workup. Liver fibrosis, tissue SOX9 and HPC expressions were studied in both BA and non-BA-cholestasis cases. Liver fibrosis, SOX9, and HPCs' dynamic changes in BA cases were assessed. Relation of fibrosis and its progression to SOX9 and HPCs in BA was assessed.
SOX9 and HPCs in ductular reaction (DR) form were expressed in 100% of BA and their grades increased significantly in the second biopsy. The rapidly progressive fibrosis in BA, represented by fibrosis grade of the intraoperative LB, correlated significantly to SOX9-DR and HPC-DR at the diagnostic (r = 0.420, P = 0.003 and r = 0.405, P = 0.004, respectively) and the intraoperative (r = 0.460, P = 0.001 and r = 0.467, P = 0.001, respectively) biopsy. On the other hand, fibrosis, SOX9-DR, and HPC-DR were significantly lower in non-BA cases at a comparable age (P < 0.001, P = 0.006, and P = 0.014, respectively).
Fibrosis in BA is rapidly progressive within a short time and is significantly correlated to SOX9 and HPCs. Assessment of targeting SOX9 and HPCs on fibrosis progression is warranted.
即使在胆道闭锁（BA）的手术成功病例中，肝纤维化也是发病率的一个重要决定因素。导致纤维化快速进展的因素尚未完全明确。转录因子 SOX9 的异常表达和肝祖细胞（HPCs）的增殖在胆汁淤积性疾病的纤维化形成中起作用。然而，它们在 BA 中的研究还不够充分。我们旨在阐明 SOX9 和 HPCs 与 BA 中的纤维化及其进展的关系。
招募了 48 例接受初次诊断性肝活检（LB）和随后的术中 LB 的 BA 患者，并与 28 例具有诊断性工作的非 BA 胆汁淤积患者进行比较。研究了 BA 和非 BA 胆汁淤积患者的肝纤维化、组织 SOX9 和 HPC 表达。评估了 BA 病例中肝纤维化、SOX9 和 HPCs 的动态变化。评估了 BA 中纤维化及其进展与 SOX9 和 HPCs 的关系。
100%的 BA 中均有胆管反应（DR）中 SOX9 和 HPCs 的表达，其在第二次活检中的分级显著增加。以术中 LB 的纤维化分级为代表的 BA 中快速进展的纤维化与诊断时的 SOX9-DR 和 HPC-DR 显著相关（r=0.420，P=0.003 和 r=0.405，P=0.004）和术中（r=0.460，P=0.001 和 r=0.467，P=0.001）活检。另一方面，在可比年龄时，非 BA 病例的纤维化、SOX9-DR 和 HPC-DR 显著降低（P<0.001，P=0.006 和 P=0.014）。
BA 中的纤维化在短时间内迅速进展，与 SOX9 和 HPCs 显著相关。评估针对 SOX9 和 HPCs 的纤维化进展具有一定的必要性。
