■原发性硬化性胆管炎(PSC),原发性胆汁性胆管炎(PBC)和自身免疫性肝炎(AIH)是表型上不同的自身免疫性肝病,进展为肝硬化和肝衰竭;然而,它们的组织学纤维化分布不同。我们调查了PSC患者的细胞外基质(ECM)分布,PBC,和AIH以确定疾病是否显示ECM周转的差异模式。
■回顾性地从英国(测试队列;PSCn=78;PBCn=74;AIHn=58)和挪威(验证队列;PSCn=138;PBCn=28;AIHn=27)收集血清样本。无肝病的溃疡性结肠炎患者(n=194)作为对照。我们评估了ECM更新的特定血清学生物标志物:III型和V型胶原蛋白形成(PRO-C3,PRO-C5),III型和IV型胶原蛋白的降解(C3M,C4M),biglycan(BGM)和瓜氨酸波形蛋白(VICM)。
■与PSC或AIH相比,大多数ECM标记物显示PBC中的血清水平升高(p<0.01)。PRO-C3与肝脏硬度相关良好,并且在晚期和非晚期肝病之间显示出最明显的差异;其他一些ECM标记物也与分期相关。PRO-C3和其他ECM标志物与PBC的熊去氧胆酸治疗反应和AIH的缓解呈负相关。PSC患者的所有ECM重塑标志物均显着升高(p<0.05),PBC,或AIH与溃疡性结肠炎相比。
■在这项比较自身免疫性肝病的ECM更新的第一项研究中,我们发现与PSC或AIH相比,PBC中的ECM周转率增加。研究表明,PSC中的ECM重塑是不同的,PBC,AIH,建议不同的治疗干预机会。
瘢痕形成的程度与自身免疫性肝病如原发性硬化性胆管炎的预后有关,原发性胆汁性胆管炎,和自身免疫性肝炎;因此,瘢痕形成过程是新疗法的可能靶点。使用高度特定的技术调查疤痕形成过程,我们发现3种自身免疫性肝病的瘢痕形成过程不同,这可能对医疗的发展具有重要意义。
UNASSIGNED: Primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) are phenotypically distinct autoimmune liver diseases that progress to cirrhosis and liver failure; however, their histological fibrosis distribution differs. We investigated the extracellular matrix (ECM) profiles of patients with PSC, PBC, and AIH to establish whether the diseases display differential patterns of ECM turnover.
UNASSIGNED: Serum samples were retrospectively collected from the UK (test cohort; PSC n = 78; PBC n = 74; AIH n = 58) and Norway (validation cohort; PSC n = 138; PBC n = 28; AIH n = 27). Patients with ulcerative colitis without liver disease (n = 194) served as controls. We assessed specific serological biomarkers of ECM turnover: type III and V collagen formation (PRO-C3, PRO-C5), degradation of type III and IV collagen (C3M, C4M), biglycan (BGM) and citrullinated vimentin (VICM).
UNASSIGNED: Most of the ECM markers showed elevated serum levels in PBC compared with PSC or AIH (p <0.01). PRO-C3 correlated well with liver stiffness and showed the most striking differences between advanced and non-advanced liver disease; several of the other ECM markers were also associated with stage. PRO-C3 and other ECM markers were inversely associated with ursodeoxycholic acid treatment response in PBC and remission in AIH. All ECM remodelling markers were significantly elevated (p <0.05) in patients with PSC, PBC, or AIH compared with ulcerative colitis.
UNASSIGNED: In this first study comparing ECM turnover in autoimmune liver diseases, we found increased ECM turnover in PBC compared with either PSC or AIH. The study indicates that ECM remodelling is different in PSC, PBC, and AIH, suggesting differing opportunities for therapeutic intervention.
UNASSIGNED: The level of scarring is linked to prognosis in autoimmune liver diseases such as primary sclerosing cholangitis, primary biliary cholangitis, and autoimmune hepatitis; hence, the scarring process is a possible target for novel therapy. Investigating the scarring process using highly specific technology, we show that the scarring process is different between the 3 autoimmune liver diseases, and this may have important implications for the development of medical treatment.