Role of ductular reaction and ductular-canalicular junctions in identifying severe primary biliary cholangitis.
Role of ductular reaction and ductular-canalicular junctions in identifying severe primary biliary cholangitis.
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DOI：
10.1016/j.jhepr.2022.100556
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发表时间：
2022-11
期刊：
影响因子：
8.3
通讯作者：
Carbone, Marco
中科院分区：
文献类型：
--
作者：
Overi, Diletta;Carpino, Guido;Cristoferi, Laura;Onori, Paolo;Kennedy, Lindsey;Francis, Heather;Zucchini, Nicola;Rigamonti, Cristina;Vigano, Mauro;Floreani, Annarosa;D'Amato, Daphne;Gerussi, Alessio;Venere, Rosanna;Alpini, Gianfranco;Glaser, Shannon;Alvaro, Domenico;Invernizzi, Pietro;Gaudio, Eugenio;Cardinale, Vincenzo;Carbone, Marco
原发性胆管炎（PBC）是一种慢性胆管疾病，其特征是免疫介导的小叶间胆管损伤，导致肝内胆汁淤积和进行性肝纤维化。PBC组织学特征为门静脉炎症、进行性纤维化、导管减少和所谓的导管反应的出现。本研究的目的是探讨胆管反应在PBC的发病相关性。从PBC初治患者（N = 87）中收集肝活检。在诊断时和熊去氧胆酸（UDCA）治疗1年后获得临床血清学参数。根据PBC的多个评分系统和标准对所有载玻片进行组织学分期。从接受或不接受UDCA处理的Mdr 2 −/−小鼠中获得肝脏样本。对样本进行组织学、免疫组织化学和免疫荧光处理。PBC患者的胆管反应与疾病分期和肝纤维化相关，但与疾病活动性无关;广泛的胆管反应与诊断时的血清碱性磷酸酶水平、对UDCA的反应和个体的估计生存率相关，独立于其他组织学参数，包括疾病分期。在PBC患者中，反应性小管与胆小管连接处的建立和纤维细胞活化有关。因此，在肝内胆汁淤积小鼠模型中，UDCA治疗可有效减少小管反应和纤维化，并增加小管-小管连接。广泛的胆管反应是PBC的一种严重的组织学表型，与治疗反应不足和估计预后较差有关。在原发性胆管炎（PBC）患者中，广泛胆管反应的组织学表现可识别出有进行性纤维化风险的个体。诊断时的小管反应与熊去氧胆酸一线治疗缺乏反应相关，有助于PBC患者恢复小管-小管连接。在诊断时评估小管反应的扩展可能为临床医生增加有价值的信息。胆管反应是PBC患者严重疾病的组织学标志。显著的小管反应与UDCA治疗反应不足相关。小管反应暗示维持小管-小管连接的完整性。胆管反应是PBC患者纤维形成的重要因素。在小鼠胆汁淤积中，UDCA可改善小管连接和纤维化。
Primary biliary cholangitis (PBC) is a chronic cholangiopathy characterised by immuno-mediated injury of interlobular bile ducts leading to intrahepatic cholestasis and progressive liver fibrosis. PBC histology is characterised by portal inflammation, progressive fibrosis, ductopenia, and the appearance of the so-called ductular reaction. The aim of the present study was to investigate the pathogenetic relevance of ductular reaction in PBC. Liver biopsies were collected from naïve people with PBC (N = 87). Clinical–serological parameters were obtained at diagnosis and after 1 year of ursodeoxycholic acid (UDCA) treatment. Histological staging was performed on all slides according to multiple scoring systems and criteria for PBC. Liver samples were obtained from Mdr2−/− mice treated with or without UDCA. Samples were processed for histology, immunohistochemistry, and immunofluorescence. Ductular reaction in people with PBC correlated with the disease stage and liver fibrosis, but not with disease activity; an extensive ductular reaction correlated with serum alkaline phosphatase levels at diagnosis, response to UDCA, and individuals’ estimated survival, independently from other histological parameters, including disease stage. In people with PBC, reactive ductules were associated with the establishment of junctions with bile canaliculi and with fibrogenetic cell activation. Consistently, in a mouse model of intrahepatic cholestasis, UDCA treatment was effective in reducing ductular reaction and fibrosis and increasing ductular–canalicular junctions. Extensive ductular reaction outlines a severe histologic phenotype in PBC and is associated with an inadequate therapy response and a worse estimated prognosis. In people affected by primary biliary cholangitis (PBC), the histological appearance of extensive ductular reaction identifies individuals at risk of progressive fibrosis. Ductular reaction at diagnosis correlates with the lack of response to first-line therapy with ursodeoxycholic acid and serves to restore ductular–canalicular junctions in people with PBC. Assessing ductular reaction extension at diagnosis may add valuable information for clinicians. Ductular reaction is a histological hallmark of severe disease in people with PBC. Prominent ductular reaction is associated with an inadequate response to UDCA therapy. Ductular reaction is implied in maintaining ductular–canalicular junction integrity. Ductular reaction is implied in fibrogenesis in people with PBC. In murine cholestasis, UDCA improves ductular–canalicular junctions and fibrosis.
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DOI：
10.1002/hep.30150
发表时间：
2019-01
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Sato K;Marzioni M;Meng F;Francis H;Glaser S;Alpini G
通讯作者：
Alpini G
DOI：
10.1016/j.bbadis.2017.09.019
发表时间：
2018-04-01
影响因子：
6.2
作者：
Cariello, Marica;Piccinin, Elena;Moschetta, Antonio
通讯作者：
Moschetta, Antonio
影响因子：
3.4
作者：
Warnes, Thomas;Roberts, Stephen;McMahon, Raymond F.
通讯作者：
McMahon, Raymond F.
DOI：
10.1016/s2468-1253(18)30163-8
发表时间：
2018-09
期刊：
The lancet. Gastroenterology & hepatology
影响因子：
--
作者：
Carbone M;Nardi A;Flack S;Carpino G;Varvaropoulou N;Gavrila C;Spicer A;Badrock J;Bernuzzi F;Cardinale V;Ainsworth HF;Heneghan MA;Thorburn D;Bathgate A;Jones R;Neuberger JM;Battezzati PM;Zuin M;Taylor-Robinson S;Donato MF;Kirby J;Mitchell-Thain R;Floreani A;Sampaziotis F;Muratori L;Alvaro D;Marzioni M;Miele L;Marra F;Giannini E;Gaudio E;Ronca V;Bonato G;Cristoferi L;Malinverno F;Gerussi A;Stocken DD;Cordell HJ;Hirschfield GM;Alexander GJ;Sandford RN;Jones DE;Invernizzi P;Mells GF;Italian PBC Study Group and the UK–PBC Consortium
通讯作者：
Italian PBC Study Group and the UK–PBC Consortium
影响因子：
5.6
作者：
Overi D;Carpino G;Cardinale V;Franchitto A;Safarikia S;Onori P;Alvaro D;Gaudio E
通讯作者：
Gaudio E