Fatigue in Primary Biliary Cholangitis: Factors Associated With Severity and Persistence as Future Therapeutic Targets (RU SOMACROSS)

疲劳是原发性胆管炎(PBC)患者的常见症状，也是治疗中未得到满足的主要需求。很少有前瞻性研究涉及PBC相关性疲劳随时间和组织学分级的发展。同时，很少有生物学和心理社会危险因素和机制可以解释PBC疲劳的发展和维持。为了在早期识别有严重疲劳风险的患者，需要进行前瞻性研究，应用全面的方法，综合观点，整合潜在的疲劳的生物医学和心理危险因素。我们项目的总体目标是确定决定疲劳过程和严重程度的因素，作为PBC中未得到满足的主要临床需求，并在可交付的干预措施中针对这些因素，以提高我们患者的生活质量。在我们为期12个月的前瞻性队列研究的横断面部分，我们的目标是同时检查临床相关的生物医学和心理社会因素，并系统地评估和比较240名PBC患者(受疲劳严重影响的患者组)和240名PSC患者(受疲劳影响小得多的对照胆汁淤积性肝病组)这些因素与疲劳之间的关联和相互作用。在未来的部分，我们将纵向监测这些变量，以确定决定疲劳严重程度的因素。为了通过自我报告以外的证据来补充我们的定量数据，我们将在n=48名新诊断的PBC患者的子样本中嵌入实验研究和定性访谈。这两种方法都是深入探索疲劳感知、发展和维持机制的宝贵机会。通过在前瞻性设计中应用混合方法，我们将获得关于生物医学和心理社会风险因素对疲劳的预测作用的创新知识，这些因素容易发生变化。这将增进我们对PBC-疲劳病因的理解，并使减少疲劳的干预措施的设计成为可能。就RU SOMACROSS的总体目标而言，我们将为开发持续躯体症状的疾病覆盖的多变量预测模型做出贡献，这将有助于跨疾病和医学学科对慢性症状的共同理解。

Fatigue is a common symptom and the major ‘unmet need’ in the management of patients with primary biliary cholangitis (PBC). There are few prospective studies that address the development of PBC-associated fatigue over time and histologic grades. At the same time, few biological and psychosocial risk factors and mechanisms have been identified that could explain the development and maintenance of fatigue in PBC. In order to identify patients at risk for severe fatigue at an early stage, prospective studies that apply a comprehensive approach, synthesizing perspectives and integrating potential biomedical and psychological risk factors of fatigue are needed. It is the overall aim of our project to identify factors that determine the course and severity of fatigue as the main unmet clinical need in PBC, and to target these factors within deliverable interventions, in order to improve quality of life for our patients. In a cross-sectional part of our prospective twelve-month cohort study, we aim to simultaneously examine clinically relevant biomedical and psychosocial factors, and systematically assess and compare associations and interactions between these factors and fatigue in n = 240 patients with PBC (a patient group severely affected by fatigue) and n = 240 patients with PSC (a control cholestatic liver disease group much less affected by fatigue). In a prospective part, we will longitudinally monitor these variables to identify factors that determine the severity of fatigue over time. In order to complement our quantitative data by evidence other than self-report, we will embed an experimental study and qualitative interviews in a subsample of n = 48 patients with newly diagnosed PBC. Both approaches represent a valuable opportunity for an in-depth exploration of mechanisms of fatigue perception, development and maintenance. By applying a mixed method approach within a prospective design, we will gain innovative knowledge on the predictive role of biomedical and psychosocial risk factors for fatigue that are amenable to change. This will enhance our understanding of the aetiology of PBC-fatigue and enable the design of interventions to reduce fatigue. In terms of the overall aims of RU SOMACROSS, we will contribute to the development of a disease-overarching multivariable prediction model for persistent somatic symptoms, which will facilitate a common understanding of chronic symptoms across diseases and medical disciplines.