Factors associated with severity and persistence of fatigue in patients with primary biliary cholangitis: study protocol of a prospective cohort study with a mixed-methods approach (SOMA.LIV).

Introduction: Fatigue is a common symptom and the major 'unmet need' in the management of patients with primary biliary cholangitis (PBC). To date, only few prospective studies have addressed the development of PBC-associated fatigue over time. 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. It is the overall aim of this study to identify factors that determine the course and severity of fatigue in PBC, and to target these factors within deliverable interventions in order to improve patients' quality of life.

Methods And Analysis: To identify biological and psychosocial risk factors for severe fatigue, a prospective 12-month cohort study with one baseline and two follow-up measurements will be conducted. In a cross-sectional part, we will 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 primary sclerosing cholangitis, a control cholestatic liver disease group much less affected by fatigue. In a prospective part, we will longitudinally monitor these variables and assess their predictive value at 12-month follow-up. Within an embedded mixed-methods design, we will conduct an experimental study and qualitative interviews in patients with newly diagnosed PBC.

Ethics And Dissemination: The study was approved by the Ethics Committee of the Hamburg Medical Association (2020-10196-BO-ff). The study will shed light onto the mechanisms underlying the evolvement and maintenance of fatigue in patients with PBC and enable the development of evidence-based intervention strategies. Findings will be disseminated through peer-reviewed publications, scientific conferences and the involvement of relevant stakeholders, patients and the lay public.

Trial Registration Number: ISRCTN14379650.