Sylvia Drazilova, Tomas Koky, Marian Macej, Martin Janicko, Dagmar Simkova, Peter Jarcuska
2nd Department of Internal Medicine, Faculty of Medicine and Louis Pasteur University Hospital, Pavol Jozef Safarik University, Kosice, Slovakia.
Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine (IKEM), Prague 4, Czech Republic.
Therap Adv Gastroenterol. 2024 Jul 29;17:17562848241265782. doi: 10.1177/17562848241265782. eCollection 2024.
Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic disease characterized by the destruction of the small intrahepatic bile ducts, which can progress to liver cirrhosis. The gold standard in the treatment of PBC is ursodeoxycholic acid (UDCA), which is indicated in all patients with PBC because it improves not only biochemical parameters but also patients' survival. An important milestone in the identification of patients at risk is the assessment of biochemical response to UDCA. Patients who respond to treatment have a lower incidence of hepatic events and better prognosis than patients who do not. Several scoring systems can be used to assess the response and identify non-responders who will benefit from second-line treatment. Obeticholic acid (OCA) is currently the only approved second-line treatment for PBC, which is effective for non-responders to UDCA therapy or patients, who have not tolerated UDCA therapy. However, OCA is contraindicated in advanced liver cirrhosis and portal hypertension. Moreover, pruritus may be a limiting factor for the administration of OCA. Fibrates have shown promising data supporting their use in non-responders to UDCA because they improve the biochemical parameters and elastographic findings and have possible antipruritic effects. Therefore, the idea of a triple treatment seems interesting. Clinical research is focusing on several other groups of drugs: peroxisome proliferator-activated receptor (PPAR) δ- and α/δ agonists, non-steroidal farnesoid X receptor agonists, fibroblast growth factor 19 modulators, and inhibitors of nicotinamide adenine dinucleotide phosphate oxidase 1 and 4.
原发性胆汁性胆管炎（PBC）是一种慢性自身免疫性胆汁淤积性疾病，其特征是肝内小胆管遭到破坏，病情可进展为肝硬化。PBC治疗的金标准是熊去氧胆酸（UDCA），所有PBC患者均适用，因为它不仅能改善生化指标，还能提高患者生存率。识别高危患者的一个重要里程碑是评估对UDCA的生化反应。对治疗有反应的患者比无反应的患者肝脏事件发生率更低，预后更好。有几种评分系统可用于评估反应并识别将从二线治疗中获益的无反应者。奥贝胆酸（OCA）是目前唯一获批用于PBC的二线治疗药物，对UDCA治疗无反应或不耐受UDCA治疗的患者有效。然而，OCA在晚期肝硬化和门静脉高压患者中禁用。此外，瘙痒可能是OCA给药的一个限制因素。贝特类药物已显示出有前景的数据支持其用于UDCA无反应者，因为它们能改善生化指标和弹性成像结果，并可能有止痒作用。因此，三联治疗的想法似乎很有意思。临床研究正聚焦于其他几类药物：过氧化物酶体增殖物激活受体（PPAR）δ和α/δ激动剂、非甾体类法尼醇X受体激动剂、成纤维细胞生长因子19调节剂以及烟酰胺腺嘌呤二核苷酸磷酸氧化酶1和4的抑制剂。
