Calgary Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Institute of Cellular Medicine, University of Newcastle, Newcastle upon Tyne, UK.
Liver Int. 2019 Jan;39(1):6-19. doi: 10.1111/liv.13919. Epub 2018 Aug 10.
The management of fatigue associated with chronic liver disease is a complex and major clinical challenge. Although fatigue can complicate many chronic diseases, it is particularly common in diseases with an inflammatory component. Fatigue can have both peripheral (i.e., neuromuscular) and central (i.e., resulting from changes in neurotransmission within the brain) causes. However, fatigue in chronic liver disease has strong social/contextual components and is often associated with behavioural alterations including depression and anxiety. Given the increasing awareness of patient-reported outcomes as important components of treatment outcomes and clinical research, there is a growing need to better understand and manage this poorly understood yet debilitating symptom. Although several pathophysiological mechanisms for explaining the development of fatigue have been generated, our understanding of fatigue in patients with chronic liver disease remains incomplete. A better understanding of the pathways and neurotransmitter systems involved may provide specific directed therapies. Currently, the management of fatigue in chronic liver disease can involve a combined use of methods to beneficially alter behavioural components and pharmacological interventions, of which several treatments have potential for the improved management of fatigue in chronic liver disease. However, evidence and consensus are lacking on the best approach and the most appropriate biochemical target(s) whilst clinical trials to address this issue have been few and limited by small sample size. In this review, we outline current understanding of the impact of fatigue and related symptoms in chronic liver disease, discuss theories of pathogenesis, and examine current and emerging approaches to its treatment.
慢性肝脏疾病相关疲劳的管理是一个复杂且重大的临床挑战。尽管疲劳可能使许多慢性疾病复杂化，但它在具有炎症成分的疾病中尤为常见。疲劳可能有外周（即神经肌肉）和中枢（即源自大脑内神经递质传递变化）原因。然而，慢性肝脏疾病中的疲劳具有强烈的社会/背景成分，并且常常与行为改变有关，包括抑郁和焦虑。鉴于人们越来越意识到患者报告的结果是治疗结果和临床研究的重要组成部分，因此越来越需要更好地理解和管理这种尚未完全了解但使人衰弱的症状。尽管已经提出了几种解释疲劳发展的病理生理机制，但我们对慢性肝脏疾病患者疲劳的理解仍然不完整。更好地了解涉及的途径和神经递质系统可能会提供特定的靶向治疗。目前，慢性肝脏疾病疲劳的管理可以包括联合使用方法来有益地改变行为成分和药物干预，其中几种治疗方法有可能改善慢性肝脏疾病的疲劳管理。然而，在这个问题上的临床试验很少且受到样本量小的限制，因此在最佳方法和最合适的生化靶点方面缺乏证据和共识。在这篇综述中，我们概述了慢性肝脏疾病中疲劳和相关症状的影响，讨论了发病机制的理论，并研究了其治疗的当前和新兴方法。
