Increased hepatic progenitor cell response and ductular reaction in patients with severe recurrent HCV post-liver transplantation.

Increased hepatic progenitor cell response and ductular reaction in patients with severe recurrent HCV post-liver transplantation.
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肝移植后严重复发性 HCV 患者的肝祖细胞反应和导管反应增加。

DOI:
10.1111/ctr.12740
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发表时间:
2016
影响因子:
2.1
通讯作者:
Schiano,ThomasD
Schiano,ThomasD
中科院分区:
医学3区
文献类型:
--
作者:
Sclair,SethN;Fiel,MariaIsabel;Wu,Hai-Shan;Doucette,John;Aloman,Costica;Schiano,ThomasD

文献摘要

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目的肝移植后(LT)丙型肝炎病毒(HCV)患者可能会发展为同种异体移植肝硬化和罕见的纤维化胆汁淤积性肝炎(FCH),而其他患者则病程稳定。肝祖细胞(HPC)可能通过导管反应(DR)参与肝损伤和纤维形成。我们研究了三种不同的 HCV LT 后模式的 HPC 反应和 DR:稳定复发、同种异体移植肝硬化和 FCH。方法我们确定了 52 名未经治疗的复发性 HCV 和纵向肝活检患者(20 名稳定/23 肝硬化/9 FCH)和 8 名健康对照。对三个时间点(LT、初次复发和临床结果)存档的肝活检标本进行细胞角蛋白-7 染色。使用图像分析进行手动 HPC 计数和 DR 定量。结果 LT 时的 HCV 计数和 DR 在各组之间没有差异。初次复发时,HPC 扩张仅发生在发展为肝硬化的患者中,而发展为 FCH 的患者与稳定对照患者相比,出现了显着的 DR(p < 0.05)。在结果活检中,与稳定对照相比,肝硬化和 FCH 的 HPC 反应和 DR 有所增加 (p < 0.05)。 HPC 响应和 DR 与不稳定状态没有区别。结论这些发现表明,LT 后通过细胞角蛋白-7 染色评估的 HPC 反应的改变可以预测 HCV 复发的严重程度。
ObjectivesPost‐liver transplant (LT) hepatitis C virus (HCV) patients may develop allograft cirrhosis and rarely fibrosing cholestatic hepatitis (FCH), while others have a stable course. Hepatic progenitor cells (HPC) may be implicated in liver injury and fibrogenesis through ductular reaction (DR). We studied HPC response and DR in three distinct post‐LT patterns of HCV:stablerecurrence, allograftcirrhosis, andFCH.MethodsWe identified 52 patients with untreated recurrent HCV and longitudinal liver biopsies (20stable/23cirrhosis/9FCH) and eight healthy controls. Archived liver biopsy specimens for three time points (LT; initial recurrence; and clinical outcome) were stained for cytokeratin‐7. Manual HPC counts and DR quantification using image analysis were performed.ResultsHCV counts and DR at LT did not differ across groups. At initial recurrence, HPC expansion occurred only in patients who developedcirrhosis, while prominent DR was present in those who developedFCHvs.stableand controls (p < 0.05). At outcome biopsies, HPC response and DR were increased incirrhosisandFCHvs.stableand controls (p < 0.05). HPC response and DR did not differ instablevs. controls.ConclusionsThese findings suggest that an altered HPC response assessed by cytokeratin‐7 stain after LT may predict severity of HCV recurrence.