Division of Gastroenterology and Hepatology, Department of Medicine, Medical University of Graz, 8036 Graz, Austria; email:
Annu Rev Pharmacol Toxicol. 2020 Jan 6;60:503-527. doi: 10.1146/annurev-pharmtox-010818-021059. Epub 2019 Sep 10.
Though ursodeoxycholic acid (UDCA) remains the baseline treatment for most cholestatic liver diseases, UDCA treatment leaves approximately one-third of patients with primary biliary cholangitis (PBC) and all patients with primary sclerosing cholangitis (PSC) at risk for disease progression. New anticholestatic agents, including nuclear receptor agonists, choleretics, and bile acid synthesis suppressors, will likely increase response rates to therapy in PBC and PSC. Strategies that target early immune-mediated injury have so far been disappointing, hampered by the lack of biomarkers to detect early disease states, which then could profit from immunomodulatory therapy. Future concepts need to personalize treatments according to disease stage, progression, and phase, and to combine multiple drugs to target different pathogenic pathways.
尽管熊去氧胆酸（UDCA）仍然是大多数胆汁淤积性肝病的基础治疗方法，但 UDCA 治疗仍使大约三分之一的原发性胆汁性胆管炎（PBC）患者和所有原发性硬化性胆管炎（PSC）患者面临疾病进展的风险。新的抗胆汁淤积药物，包括核受体激动剂、胆汁分泌剂和胆汁酸合成抑制剂，可能会提高 PBC 和 PSC 的治疗反应率。针对早期免疫介导损伤的策略迄今为止令人失望，这是由于缺乏生物标志物来检测早期疾病状态，从而无法从免疫调节治疗中获益。未来的概念需要根据疾病阶段、进展和分期来个性化治疗，并结合多种药物来针对不同的致病途径。
