Primary Biliary Cholangitis
Primary Biliary Cholangitis
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原发性胆汁性胆管炎
DOI：
10.1002/9781119237662.ch17
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发表时间：
2018
期刊：
影响因子：
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中科院分区：
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原发性胆管炎(PBC)，以前被称为原发性胆汁性肝硬变，被指定为孤儿，是一种慢性自身免疫性疾病，导致肝脏小胆管的破坏。像其他复杂的疾病一样，PBC在感觉前、症状、疾病进展和对治疗的反应方面是不同的。如果没有有效的治疗，疾病的发展往往会导致肝功能衰竭和死亡。直到2016年5月，牛胆酸(OCA)被批准作为PBC患者的治疗选择，FDA批准的唯一治疗PBC的药物是熊去氧胆酸(UDCA)，这是一种口服亲水性胆汁酸，可以减缓PBC引起的肝脏损害的进展。然而，每3名服用UDCA的患者中就有1名生化反应不足，导致疾病进展、肝移植和死亡的风险增加。鉴于这一未得到满足的临床需求，治疗PBC的新疗法正在开发中。有针对免疫介导性反应的分子和针对胆汁酸生物合成和反馈过程的胆汁酸治疗，这些过程驱动胆管上皮细胞损伤。此外，抗纤维化治疗正在研究中，以解决胆道损伤后的下游损害。总而言之，PBC是一种表型不均、特征不佳的疾病，目前治疗选择有限。
Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis and which has been designated an orphan condition, is a chronic autoimmune disease resulting in the destruction of the small bile ducts in the liver. Like other complex disorders, PBC is heterogeneous in its pre-sensation, symptomatology, disease progression and response to therapy. Without effective treatment, disease progression frequently leads to liver failure and death. Until May 2016, when Obeticholic acid (OCA) has been licensed as treatment options for patients with PBC, the only FDA-approved treatment for PBC was Ursodeoxycholic acid (UDCA), an oral hydrophilic bile acid, which can slow progression of liver damage due to PBC. However, 1 out of 3 patients taking UDCA has an inadequate biochemical response, leading to increased risk of disease progression, liver transplantation, and mortality. Given this unmet clinical need, new therapies are in development for the treatment of PBC. There are molecules targeting the immune-mediated response and bile-acid therapies targeting the bile acid biosynthetic and feedback processes that drive the biliary epithelial cells injury. In addition, antifibrotic therapies are under study to tackle the downstream damage following biliary injury. In conclusion, PBC is a condition with a heterogeneous, poorly characterized phenotype for which limited therapeutic options are currently available.