Abbas Nadir, Quraishi Mohammad Nabil, Trivedi Palak
Liver Unit, University Hospitals Birmingham Queen Elizabeth, Birmingham, UK; NIHR Birmingham Biomedical Research Centre, Centre for Liver and Gastroenterology Research, University of Birmingham, UK; Institute of Immunology and Immunotherapy, University of Birmingham, UK.
Department of Gastroenterology, University Hospital Birmingham NHS Trust, UK; University of Birmingham Microbiome Treatment Centre, University of Birmingham, UK.
Curr Opin Pharmacol. 2022 Feb;62:23-35. doi: 10.1016/j.coph.2021.11.003. Epub 2021 Dec 8.
Primary sclerosing cholangitis (PSC) is a rare immune-mediated cholestatic disease for which no medical therapy has been shown to slow disease progression. Consequently, liver transplantation is the only lifesaving intervention for patients, and despite being a rare disease, PSC is the lead indication for transplantation across several European countries. The vast majority of patients (>70%) also develop inflammatory bowel disease (IBD) at some point in their lifetime, which imparts added lifetime risks of hepatobiliary malignancy and colorectal cancer. The rare disease nature, variable and often slow rates of disease progression (years rather than months), and lack of robust surrogate biomarkers for early stage yet high risk disease, represent critical challenges in trial design that have long precluded the development of effective medical treatment. However, the horizon for new treatments is encouraging, given innovative clinical trial programmes led by industry, alongside several investigator-initiated studies. Herein, we outline the current platform of interventional trials in PSC, before discussing emerging areas of therapeutic interest.
原发性硬化性胆管炎（PSC）是一种罕见的免疫介导性胆汁淤积性疾病，尚无药物治疗被证明能减缓疾病进展。因此，肝移植是患者唯一的救命干预措施，尽管PSC是一种罕见疾病，但在几个欧洲国家，它是肝移植的主要指征。绝大多数患者（>70%）在其一生中的某个阶段还会发生炎症性肠病（IBD），这增加了患肝胆恶性肿瘤和结直肠癌的终生风险。罕见病的性质、疾病进展的可变且通常缓慢的速度（数年而非数月）以及缺乏用于早期但高危疾病的可靠替代生物标志物，是试验设计中的关键挑战，长期以来阻碍了有效药物治疗的开发。然而，鉴于行业主导的创新临床试验项目以及多项研究者发起的研究，新治疗方法的前景令人鼓舞。在此，我们概述了PSC介入试验的当前平台，然后讨论了新兴的治疗关注领域。
