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SOX9 in biliary atresia: New insight for fibrosis progression
Hepatobiliary & Pancreatic Diseases International ( IF 3.6 ) Pub Date : 2020-12-09 , DOI: 10.1016/j.hbpd.2020.12.007
Hanaa Ahmed El-Araby 1 , Magdy Anwar Saber 1 , Noha Mohamed Radwan 1 , Doha Maher Taie 2 , Nermin Mohamed Adawy 1 , Ahmad Mohamed Sira 1
Affiliation  

Background

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.

Methods

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.

Results

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).

Conclusions

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.



中文翻译:

胆道闭锁中的 SOX9:纤维化进展的新见解

背景

即使在成功手术的病例中,肝纤维化也是胆道闭锁 (BA) 发病率的标志性决定因素。导致这种纤维化快速进展的因素尚未完全确定。转录因子 SOX9 的异常表达和肝祖细胞 (HPC) 增殖在胆汁淤积性疾病的纤维化中起作用。然而,他们在 BA 中没有得到充分的研究。我们旨在描绘 SOX9 和 HPCs 与纤维化及其在 BA 中的进展的关系。

方法

招募了 48 名接受初始诊断性肝活检 (LB) 和随后的术中 LB 的 BA 患者,并与 28 名在诊断性检查中有 LB 的非 BA 胆汁淤积患者进行了比较。在 BA 和非 BA 胆汁淤积病例中研究了肝纤维化、组织 SOX9 和 HPC 表达。评估了肝纤维化、SOX9 和 HPCs 在 BA 病例中的动态变化。评估了纤维化及其与 BA 中 SOX9 和 HPCs 的关系。

结果

导管反应 (DR) 形式的 SOX9 和 HPC 在 100% 的 BA 中表达,并且它们的等级在第二次活检中显着增加。BA 中快速进展的纤维化,以术中 LB 的纤维化等级为代表,与诊断时的 SOX9-DR 和 HPC-DR 显着相关(分别为r  = 0.420,P  = 0.003 和r  = 0.405,P  = 0.004)和术中(分别为r  = 0.460,P  = 0.001 和r  = 0.467,P  = 0.001)活检。另一方面,纤维化、SOX9-DR 和 HPC-DR 在非 BA 病例中显着较低(P  < 0.001,P = 0.006 和P  = 0.014,分别)。

结论

BA 中的纤维化在短时间内迅速进展,并且与 SOX9 和 HPC 显着相关。有必要评估靶向 SOX9 和 HPC 对纤维化进展的影响。

更新日期:2020-12-09
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