Norwegian PSC Research Center, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway.
Aliment Pharmacol Ther. 2014 Feb;39(3):282-301. doi: 10.1111/apt.12581. Epub 2013 Dec 29.
Despite considerable advances over the last two decades in the molecular understanding of cholestasis and cholestatic liver disease, little improvement has been made in diagnostic tools and therapeutic strategies.
To critically review controversial aspects of the scientific basis for common clinical practice in primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) and to discuss key ongoing challenges to improve patient management.
We performed a literature search using PubMed and by examining the reference lists of relevant review articles related to the clinical management of PBC and PSC. Articles were considered on the background of the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD) practice guidelines and clinical experience of the authors.
Ongoing challenges in PBC mainly pertain to the improvement of medical therapy, particularly for patients with a suboptimal response to ursodeoxycholic acid. In PSC, development of medical therapies and sensitive screening protocols for cholangiocarcinoma represent areas of intense research. To rationally improve patient management, a better understanding of pathogenesis, including complications like pruritis and fatigue, is needed and there is a need to identify biomarker end-points for treatment effect and prognosis. Timing of liver transplantation and determining optimal regimens of immunosuppression post-liver transplantation will also benefit from better appreciation of pre-transplant disease mechanisms.
Controversies in the management of PBC and PSC relate to topics where evidence for current practice is weak and further research is needed.
尽管在过去的二十年中，在胆甾醇和胆甾醇性肝病的分子理解方面取得了相当大的进展，但在诊断工具和治疗策略方面几乎没有改进。
批判性地审查原发性胆汁性肝硬化（PBC）和原发性硬化性胆管炎（PSC）的常见临床实践的科学依据中存在争议的方面，并讨论改善患者管理的关键挑战。
我们使用 PubMed 进行了文献检索，并检查了与 PBC 和 PSC 临床管理相关的综述文章的参考文献列表。根据欧洲肝脏研究协会（EASL）和美国肝脏研究协会（AASLD）的实践指南以及作者的临床经验，对文章进行了考虑。
PBC 中的持续挑战主要涉及改善医学治疗，特别是对于对熊去氧胆酸反应不佳的患者。在 PSC 中，开发医学疗法和用于胆管癌的敏感筛查方案是激烈研究的领域。为了合理地改善患者管理，需要更好地了解发病机制，包括瘙痒和疲劳等并发症，需要确定用于治疗效果和预后的生物标志物终点。肝移植的时机和确定肝移植后最佳的免疫抑制方案也将受益于对移植前疾病机制的更好理解。
PBC 和 PSC 管理中的争议涉及到当前实践证据薄弱的主题，需要进一步研究。
