热休克蛋白47的表达与胆道闭锁肝纤维化及预后的相关性研究

目的 研究热休克蛋白47的表达与胆道闭锁患儿肝脏纤维化程度及预后的相关性.方法 选择30例胆道闭锁、10例胆汁淤积症和10例胆总管囊肿患儿入组,分别取肝脏组织以及外周血,通过RT-PCR、Western-blot、ELISA以及病理切片来评估不同水平HSP47的表达情况及其与肝脏纤维化相关性.结果 三组HSP47在mRNA水平(0.915±0.730比0.066±0.037比0.314±0.150,P＜0.05)、蛋白水平(3.061 81±0.504 763比1.358 018±0.373 174比1.23649±0.350 173,P＜0.05)以及血清水平(63.38±17.11比57.87±14.83比45.78±11.23,P＜0.05)的表达胆道闭锁组均比胆汁淤积组以及胆总管囊肿组高,差异有统计学意义,且不同水平表达具有一致性(mRNA比蛋白水平:r=0.836,P＜0.05;蛋白水平比血清水平:r=0.989,P＜0.01;mRNA比血清水平:r=0.883,P＜0.05).胆道闭锁血清HSP47的表达与肝脏组织光镜下纤维化程度呈正相关关系(r=0.669,P＜0.01).结论 肝脏组织HSP47的表达与血清HSP47的表达水平具有一致性,能够评估肝脏纤维化程度;血清HSP47的高表达可能作为胆道闭锁预后不良的一个监测指标.     

胆道闭锁异常肝组织蛋白筛查及预后相关性研究

目的 初步鉴定胆道闭锁肝组织异常蛋白表达情况,寻找与胆道闭锁发病和预后有关的差异表达蛋白.方法 用固相pH梯度双向凝胶电泳分离胆道闭锁和正常肝脏组织总蛋白,银染显色,Melanie3.02 2D图像分析软件分析,对部分蛋白质点用基质辅助激光解析电离飞行时间质谱(MALDI-TOF-MS)进行鉴定,查询数据库鉴定差异蛋白质.结果 获得了背景清晰、分辨率和重复性较好的双向凝胶电泳图谱,蛋白质匹配率达800%以上.胆道闭锁和正常组比较发现表达量变化达2倍以上的蛋白点有33个,表达量变化达4倍以上者有8个.胆道闭锁预后较好者和预后不好者比较发现表达量变化达4倍以上的蛋白点有22个,表达量变化达5倍以上者有18个.质谱鉴定其中15个点,其中7个点鉴定成功,分别是Viperin、SARM1、GPC3、APC、THUM2、MIA3和KIAA0649.结论 本研究成功鉴定出部分与胆道闭锁发病和预后有关的蛋白质,为进一步研究胆道闭锁致病机制和提高手术预后提供了新的研究方向,有进一步研究的价值.

Abstract：

Objective To investigate the expression of hepatic protein in patients with biliary atresia(BA), and find the relationship between the significant protein and prognosis of biliary atresia.Methods Immobile pH gradients isoelectric focusing was used as 1D, and vertical SDS-PAGE as 2D.Sliver staining, Melanie3. 02 2D analysis software, matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) and NCBInr database searching were used to separate and identify the proteome from liver in patients with biliary atresia. Results Satisfactory 2DE patterns were obtained. Thirty-three protein spots were remarkably changed in patients with biliary atresia compared with the control group. Twenty-two protein spots were significantly difference between BA patients with good prognosis and BA patients with poor prognosis. Fifteen protein spots were referred to mass spectrometry, and 7 protein spots were identified, including Viperin, SARM1, GPC3, APC,THUM2, MIA3 and KIAA0649. Conclusions In this study, proteins related to the prognosis and pathogenesis of biliary atresia were identified, which may contribute to prognosis and pathogenesis of biliary atresia.     

P-Smad 3在胆道闭锁肝纤维化中的作用机制研究

目的研究转化生长因子-β1(Transforming growth factor-β1,TGF-β1)、促纤维化通路中TGF-β1、P-Smad3等通路蛋白在胆道闭锁(Biliary atresia,BA)肝纤维化进程中的作用机制。方法选取2010年1月到2015年7月我们收治的胆管扩张症肝活检病例10例,为胆扩组;BA肝活检病例19例,为Kasai组;BA晚期肝移植患者自体肝活检病例11例,为移植组11例。进行苏木素/伊红(HE)、马松(Masson)染色观察肝标本纤维化评价其纤维化程度,免疫组化(Immunohistochemistry,IHC)染色检测TGF-β1、Smad2-4、P-Smad2-3及人纤溶酶原激活物抑制因子1(PAI-1)在肝组织中的表达,结合BA肝纤维化病理分级标准探讨TGF-β1等通路蛋白在肝纤维化进程中的作用。结果 HE及Masson:胆扩组偶见纤维细胞增生,Kasai组胶原纤维增生、桥接纤维化现象显著,移植组假小叶显著。免疫组化:①定性分析:胆扩组肝内Smad 2、Smad 4、PAI-1为阳性表达,其余为弱阳性;Kasai组TGF-β1等蛋白均在肝细胞胞质阳性表达,P-Smad 2、P-Smad 3、Smad4在胞核亦呈阳性表达;移植组患儿肝内TGF-β1等蛋白皆为弱阳性表达。②半定量分析:三组中Kasai组TGF-β1、Smad 3、P-Smad 3及PAI-1含量表达明显高于其他两组(P0.05),随着TGF-β1、Smad3、P-Smad3及PAI-1逐渐升高肝纤维化逐渐加重;PSmad3与PAI-1含量大小及变化幅度密切相关,促肝纤维化作用显著;Smad2、P-Smad2、Smad4组间无差异,在通路中连接相关蛋白。移植组TGF-β1等通路蛋白含量均少于Kasai组,随着肝硬化加重而逐渐减少。结论 BA肝内TGF-β1促纤维化通路中TGF-β1、Smad3显著促进肝纤维化,P-Smad3与肝纤维化进程密切相关。     

胆道闭锁肝纤维化与血清学监测

胆道闭锁（Biliary Artesia,BA）是新生儿阻塞性黄疸最常见的原因之一。其病理特征为胆管的进行性炎症和肝纤维化,发展速度快,涉及肝内外胆管,虽然通过Kasai手术（即肝门空肠吻合术）能够改善肝内外胆道的梗阻。但多数患儿仍发生进行性肝内胆管破坏和肝纤维化。最后发展为肝硬化和门静脉高压。晚期病例肝脏移植将不可避免。BA病人的预后受多种因素的影响,如Kasai手术时的年龄、病变的类型以及肝纤维化程度等。预测BA的预后以及判断肝纤维化程度。对选择肝移植的手术时机有着极其重要的意义。     

Hedgehog通路在胆道闭锁肝纤维化中的研究进展

胆道闭锁(biliary atresia,BA)是一种罕见且严重的新生儿胆汁淤积症,其特征为进行性的毛细胆管纤维梗阻性疾病。近期研究发现,Hedgehog信号通路不仅在胚胎的形态形成、生长控制、肝胆发育中起着关键作用,还参与BA肌成纤维细胞的积累和肝纤维化的发生过程。本文通过检索文献,对Hedgehog信号通路的组成以...     

表皮生长因子在胆道闭锁肝纤维化中的作用机制的研究

目的:探索表皮生长因子（epidermal growth factor,EGF）对胆管上皮细胞增殖和上皮间充质转化（epithelial mesenchymal transition,EMT）的作用,为胆道闭锁（biliary atresia, BA）肝纤维化的发生机制和治疗方向提供实验依据。方法:收集2019年1月至...     

胆道闭锁肝纤维化病变中平滑肌肌动蛋白表达的研究

目的 本研究通过检测平滑肌肌动蛋白(α-SMA)在胆道闭锁(BA)肝组织和肝外胆系的表达,探讨肝纤维化过程与临床预后的关系.方法 采用免疫组化染色方法对2005年7月至2006年5月本院21例BA肝组织、肝门纤维块进行CD68和α-SMA染色;对照组为5例胆汁淤积和10例胆总管囊肿.选用LEICA-DM研究级生物显微镜,QWIN软件环境下测量抗体阳性细胞面积百分比和平均光密度,随访19例BA术后3个月直接胆红素下降比率.同时对21例BA肝组织纤维化分级,并与α-SMA表达量进行相关分析.结果 α-SMA在BA肝纤维块高度表达于胆管上皮、胆管周围的胶原纤维;α-SMA阳性表达量和表达强度明显高于对照组,其表达量与表达强度呈线性正相关(r=0.549,P=0.022);CD68在BA肝组织表达较对照组明显增强,但肝门纤维块鲜有表达.α-SMA表达量与肝脏纤维化分级呈正相关(P=0.02);α-SMA阳性表达面积百分比与术后3个月直接胆红素下降率呈负相关(r=-0.653,P=0.029),但肝组织CD68表达与α-SMA阳性表达相关性不明显(r=0.444,P=0.057).结论 α-SMA的表达可能是肝脏纤维化的早期标志,SMA的阳性表达量与术后3个月胆红素消退呈显著负相关,预示BA肝内外胆管系统纤维化,乃至肝硬化,提示可能临床预后不佳.     

法尼醇X受体影响胆道闭锁肝纤维化机制的研究进展

<正>胆道闭锁是一种罕见的导致新生儿及婴儿胆汁淤积的先天性胆道系统疾病,以肝内外胆管进行性炎症以及肝纤维化为特征,导致胆汁在胆道内大量淤积,并最终引起肝硬化。如不及时治疗,胆道闭锁患儿往往于出生后2年内死于终末期肝病^[1-2]。胆道闭锁早期诊断困难的特性与其高病死率一直是困扰小儿外科医师的难题。     

Notch信号通路活化协同巨噬细胞对胆道闭锁肝纤维化的作用研究

目的探究Notch信号通路活化及相关炎性反应分子机制在胆道闭锁患者肝纤维化进展中的作用。方法选取2019年1月至2020年11月于天津市儿童医院确诊的20例胆道畸形患者(15例胆道闭锁,5例胆总管扩张)作为研究对象,收集临床资料及术中留取的肝活检组织样本,使用免疫组化方法检测患者肝组织内Notch信号通路的效应分子HES-1,M2型巨噬细胞标志物CD163及细胞因子IL-6、PDGF-AA的表达并进行半定量分析。结果与胆总管扩张组相比,HES-1(0.044±0.017 vs.0.143±0.027)、CD163(0.089±0.020 vs.0.259±0.111)、IL-6(0.070±0.007 vs.0.216±0.028)、PDGF-AA(0.155±0.019 vs.0.220±0.044)在胆道闭锁患者肝组织中的表达明显增加,且差异有统计学意义(P<0.05);HES-1的表达与CD163的表达呈正相关(r_s=0.687,P<0.01);HES-1、CD163、IL-6、PDGF-AA与肝纤维化程度成明显正相关(r_s=0.791,r_s=0.912,r_s=0.920,r_s=0.887,P<0.001)。结论Notch信号通路参与了胆道闭锁肝纤维化进程,并与M2型巨噬细胞有协同作用。     

JNK2、TIMP-1及Collagen Ⅲ在胆道闭锁肝纤维化中的作用研究

目的研究c-Jun氨基末端激酶2(c-Jun N-terminal kinase,JNK2)、金属蛋白酶组织抑制剂-1(tissue inhibitor of metalloproteinase 1,TIMP-1)及CollagenⅢ在胆道闭锁(BA)肝组织中的表达情况及在肝纤维化进程中的作用。方法选取胆管扩张症肝活检病例10例,为胆扩组;BA肝活检病例15例,为BA组;BA晚期因肝功能衰竭而行肝移植患者自体肝活检10例,为肝移植组。采用HE染色观察并评价肝标本纤维化程度;免疫组化染色检测JNK2、TIMP-1及CollagenⅢ在肝组织中的表达;实时荧光定量聚合酶链式反应(qRT-PCR)检测肝组织中JNK2、TIMP-1及CollagenⅢ基因表达情况。结果①HE染色:胆扩组偶可见少许纤维细胞增生;BA组汇管区增宽,纤维组织增生、桥接纤维化现象普遍,可见假小叶形成;肝移植组汇管区明显增宽,纤维组织增生较重,广泛桥接纤维组织形成,假小叶显著。②免疫组化:胆扩组JNK2、TIMP-1及CollagenⅢ表达为弱阳性,BA组及肝移植组JNK2、TIMP-1及CollagenⅢ蛋白均在肝细胞、汇管区胆管上皮细胞及血管内皮细胞胞质中阳性表达。(3)半定量分析:三组JNK2(0.122±0.008、0.182±0.017和0.198±0.033),TIMP-1(0.123±0.009、0.185±0.012和0.201±0.017)和CollagenⅢ(0.126±0.012、0.194±0.008和0.208±0.033)表达比较,差异有显著统计学意义(P0.001);三组中,BA组及肝移植组JNK2、TIMP-1及CollagenⅢ表达明显高于胆扩组(P0.05);肝移植组JNK2、TIMP-1及CollagenⅢ蛋白含量与BA组比较,差异无统计学意义(P值均0.05)。(4)qRT-PCR:三组JNK2、TIMP-1和CollagenⅢmRNA表达水平比较,差异有统计学意义(0.221(0.17)vs 1.395(1.22)vs 1.095(1.21),H=17.686,P=0.003;0.439(0.31)vs 1.404(0.85)vs 1.571(0.66),H=20.648,P=0.000;0.917(0.09)vs 1.802(1.35)vs 1.957(1.30),H=15.555,P=0.007),BA组及肝移植组肝内JNK2、TIMP-1及CollagenⅢmRNA表达含量比胆扩组高(P值均小于0.017)。结论JNK2、TIMP-1及CollagenⅢ在BA患儿随着肝纤维化加重而表达升高,表明其可能参与并促进BA肝纤维化进程。     

胆道闭锁肝纤维化与自体肝生存关系的研究进展

胆道闭锁是婴儿期最严重的肝胆系统疾病之一。肝门-空肠吻合术(Kasai手术)是治疗胆道闭锁的主要手段,但术后自体肝长期生存效果不佳,大部分患儿需要通过肝移植来挽救生命。肝纤维化是影响胆道闭锁患儿自体肝生存的重要因素之一,其发生机制复杂,涉及多种信号通路及细胞因子的调控。Kasai手术后胆汁引流不畅、胆管炎发作都会导致肝纤维化进展,进而发生肝硬化。在完善早期诊断、早期手术、通畅引流胆汁及控制胆管炎的同时,还应积极应对患儿肝纤维化的持续进展,以期达到自体肝的长期生存。     

Elevated serum heat shock protein 70 and liver stiffness reflect hepatic dysfunction and severity in postoperative biliary atresia

Background

Biliary atresia (BA) is a severe chronic liver disease characterized by progressive obstructive cholangiopathy of biliary tract. Heat shock protein 70 (HSP70) is involved in protecting cells against a wide variety of stress and plays a protective role in tissue damage. The purpose of this study was to investigate serum HSP70 and liver stiffness in BA and determine the association of serum HSP70, liver stiffness, and outcome parameters in post-Kasai BA patients.

Methods

One hundred post-Kasai BA patients and 40 controls were enrolled. Serum HSP70 levels were analyzed using enzyme-linked immunosorbent assay. Liver stiffness values were assessed by transient elastography.

Results

BA patients had significantly higher serum HSP70 and liver stiffness values than controls. Serum HSP70 and liver stiffness values were markedly elevated in BA patients with jaundice compared to those without jaundice (P < 0.001). Furthermore, serum HSP70 was more elevated in BA children with portal hypertension than those without portal hypertension (35.1 ± 2.1 vs. 27.9 ± 2.5 ng/mL, P < 0.001). Moreover, serum HSP70 was positively correlated with serum aspartate aminotransferase (r = 0.491, P < 0.001), alanine aminotransferase (r = 0.448, P < 0.001), total bilirubin (r = 0.303, P = 0.002), alkaline phosphatase (r = 0.414, P < 0.001), and liver stiffness values (r = 0.455, P < 0.001). There was a negative correlation between serum HSP70 and serum albumin (r = ?0.434, P = 0.001).

Conclusion

Serum HSP70 and liver stiffness values were higher in BA patients than controls. The increased serum HSP70 was correlated with hepatic dysfunction in BA. Consequently, serum HSP70 and liver stiffness could serve as non-invasive parameters reflecting the severity in post-Kasai BA.

     

APRI评价胆道闭锁和胆汁淤积综合征肝脏纤维化程度的临床意义

目的 探讨肝功能检查和门冬氨酸氨基转移酶/血小板指数(aspartate aminotransferase-to-platelet ratio index,APRI)与肝脏纤维化程度的关系,阐述其在BA肝纤维化评估中的临床价值.方法 收集2006年2月至2011年8月间在我院治疗的胆道闭锁患儿38例和胆汁淤积综合征患儿25例为研究对象.临床观察指标包括肝功能检查,肝脏活检切片,血小板指数;肝硬化程度采用Metavir分类,APRI的诊断性评估采用ROC曲线,应用SPSS 16.0统计学软件进行统计分析.并对本组患儿进行随访,随访时间是3～69个月(平均随访时间:20.7个月).结果 胆道闭锁组患儿ALP、γ-GT、DBIL(564.14±257.75、153.36±97.47、7.55±2.57)较胆汁淤积综合征组患儿存在明显升高(P＜0.05);胆道闭锁肝硬化组患儿Age、ALT、AST、γ-GT(84.50±24.72、225.07±109.68、331.64±130.93、951.07±667.24)较非肝硬化组明显升高,两组差异具有统计学意义(P＜0.05);胆汁淤积综合征肝纤维化组患儿Age、ALT、AST(84.76±14.28、159.92±61.76、238.15±62.60)较非肝纤维化组(54.17±11.17、98.92±58.08、151.17±41.44)明显升高,两组差异具有统计学意义(P＜0.05).患儿绘制APRI的ROC曲线,用于判定肝硬化程度,胆道闭锁组敏感性为79％,特异性为88％;胆汁淤积综合征组敏感性为91％,特异性为79％.胆道闭锁中肝硬化组病死率显著高于非肝硬化组,且自体肝生存情况低于非肝硬化组.结论 肝功能检查可以作为胆道闭锁的初步判断指标,绘制APRI的ROC曲线对于评价胆道闭锁及胆汁淤积综合征患儿的肝脏纤维化情况均有较高准确性和可靠性,可用于预测预后和提早做好肝移植准备,因其简单、无创性可以在临床上广泛应用.     

胆道闭锁患儿自身免疫性肝病抗体的筛查分析

目的 分析自身免疫性肝病相关抗体在胆道闭锁(BA)患儿血清中检出情况,探讨其在BA临床诊断及致病机制中的意义.方法 采用线性免疫印迹法分别检测81例BA组、48例疾病对照组(DC)和40例正常对照组(NC)血清中自身免疫性肝病IgG抗体,包括原发性胆汁性胆管炎相关抗体(PBC相关抗体,含AMA-M2、抗M2-3E 、抗Spl00、抗PML和抗gp210抗体)、自身免疫性肝炎相关抗体(AIH相关抗体,含抗LKM-1、抗LC-1、抗SLA/LP抗体)以及抗Ro-52抗体.结果 BA组患儿中PBC相关抗体组合检出率为18.5%,单一检出率由高到低分别为抗M2-3E抗体(14.8%)、抗PML抗体(3.7%)、抗gp210抗体(2.5%),AMA-M2(1.2%)和抗sp100抗体(1.2%),其中,抗M2-3E抗体阳性率明显高于NC组((χ)2=5.025,P=0.025),但与DC组(4.2%)无统计学差异(P>0.05).AIH相关抗体在BA患儿中仅检出抗LC-1抗体(7.4%),与DC组(6.3%)、NC组(7.5%)的检出率差异,无统计学意义(P>0.05).抗Ro-52抗体在BA、DC和NC组的检出率分别为6.2%,4.2%和5%,组间无统计学差异(P>0.05).结论 BA患儿血清中存在不同程度检出率的自身免疫性肝病抗体,PBC相关抗体检出率较高,尤其是抗M2-3E抗体.自身抗体的检出提示BA存在针对靶抗原的体液免疫,可能参与BA的免疫致病过程,但其在BA的血清学诊断意义仍待进一步研究.     

Graft fibrosis in patients with biliary atresia after pediatric living-related liver transplantation

Although an LDLT can successfully treat biliary atresia (BA), some patients develop liver fibrosis or inflammation. To study the incidence and risk factors associated with these complications, we performed serial protocol biopsies. Twenty-four patients with BA who received a pediatric LDLT underwent protocol biopsies. All patients received standard tacrolimus-based immunosuppression and steroids. The last available biopsies were assessed. The mean age at the time of transplant was 4.8yr and the follow-up period ranged from 1.2 to 12.3yr. The GRWR ranged from 0.8% to 4.5%. The mean time from transplantation to the latest biopsy was 4.7yr. No complications occurred with the biopsy protocol. The last available biopsies for 13 (54%) and 4 (17%) patients indicated grade 1 and grade 2 portal fibrosis, respectively, and 14 patients (54%) had inflammation. No ductopenia was detected. A younger age at LDLT was significantly correlated with graft fibrosis (p=0.036). These results indicate that biopsy-proven fibrosis can be detected in patients with BA after LDLT, even in the context of normal liver function blood tests. Therefore, a serial biopsy is a safe and effective follow-up procedure for pediatric LDLT.     

Inchin-ko-to prevents medium-term liver fibrosis in postoperative biliary atresia patients

The oriental herbal formulation inchin-ko-to (ICKT) inhibits liver cell apoptosis induced by transforming growth factor-beta 1 (TGF-β1). This study evaluated the effect of ICKT on serum markers of liver function and liver fibrosis in postoperative biliary atresia (BA) patients. Twenty-one postoperative BA patients with elevated GOT, GPT and γ-GTP, but normal serum total bilirubin levels, were divided into two groups arbitrarily; an ICKT group (n = 12), and a no-ICKT group (n = 9). Serum markers of liver function [GOT, GPT, γ-GTP, total bile acids (TBA)], and serum markers of liver fibrosis [hyaluronic acid (HA), type IV collagen (C-IV)], were measured in both groups at the beginning of the study, and at 1, and 3 years after the beginning of the study and the results compared statistically. All patients tolerated ICKT well, and there were no side effects. In the ICKT group, mean serum HA levels were significantly decreased at 1 year (P < 0.012), and at 3 years, both mean serum HA and C-IV were significantly decreased (P < 0.001 and P < 0.003, respectively). However, mean serum levels of GOT, GPT, γ-GTP, and TBA did not change significantly following ICKT use for any length of time (all P > 0.05). Administration of ICKT in postoperative BA patients appears to lower the serum levels of markers of fibrosis in the medium-term. Whether this in fact correlates with prevention cannot be determined from this paper, but ICKT would appear to protect against liver fibrosis. Long-term studies are required to determine the exact role ICKT plays in prognosis of BA patients.     

新生儿巨细胞病毒感染与胆道闭锁肝脏纤维化的相关研究

目的探讨新生儿巨细胞病毒感染与胆道闭锁肝脏损伤的关系。方法回顾我院2004年1月-2005年1月收治21例胆道闭锁患儿临床资料。对肝组织纤维化和肝细胞变性坏死程度分级，同时进行肝脏和肝门纤维块巨细胞病毒-pp65免疫荧光染色。根据血清及病毒学检查结果将病人分组，比较两组患儿肝功能，肝脏纤维化，肝细胞破坏程度。结果巨细胞病毒感染组13例，非感染组8例。两组肝功能各指标除总胆红素，γ-谷氨酰转肽酶外无明显差异。巨细胞病毒感染组肝脏纤维化程度重于非感染组（P〈0．05）。结论巨细胞病毒活动性感染加重胆道闭锁患儿胆汁淤积和肝脏的纤维化。     

Fn14 hepatic progenitor cells are associated with liver fibrosis in biliary atresia

Purpose

The liver in biliary atresia (BA) is characterized by progressing fibrosis which is promoted by unclear reasons. We aimed to understand the factors influencing liver fibrosis. This study hypothesized that HPCs (hepatic progenitor cells) are activated and associated with liver fibrosis in biliary atresia.

Methods

Liver samples from biliary atresia patients are as BA group, and the normal liver derived from hepatoblastoma infants during operation are control group. The extent of fibrosis in liver samples was blindly evaluated by two experienced pathologists depending on Ishak system. The BA liver samples were divided into mild liver fibrosis group (grade I–IV, BA_a) and severe liver fibrosis group (grade V–VI, BA_b) to detect Fn14 protein expression.

Results

In mRNA level, Fn14 expression was 21.23?±?8.3 vs. 1.00?±?0.17, p?=?0.023?<?0.05 and CD133 expression was 6.02?±?2.16 vs. 1.14?±?0.75, p?=?0.008?<?0.01 between BA group and control group. Fn14 cells co-expressed the progenitor marker CD133 in liver, and activated in BA. Fn14 andα-SMA were co-location in fibrous area in liver. Compared to the control group, Fn14, CD133, and α-SMA protein expression were 2.10?±?0.53 vs. 0.97?±?0.2, p?=?0.001, 2.23?±?0.57 vs. 1.00?±?0.03, p?=?0.000, 4.96?±?2.4 vs. 1.00?±?0.22, p?=?0.001. The Fn14 protein expression was 2.60?±?0.35 vs. 1.86?±?0.42, p?=?0.012, between BA_b and BA_a group.

Conclusion

Fn14 cells, which co-express the progenitor marker CD133 in liver, are HPCs and activated in BA. Fn14?+?HPCs are associated with liver fibrosis in BA.