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Review
. 2022 Jun 27;14(6):1111-1119.
doi: 10.4254/wjh.v14.i6.1111.

Understanding fatigue in primary biliary cholangitis: From pathophysiology to treatment perspectives

Erica Nicola Lynch  1 , Claudia Campani  1 , Tommaso Innocenti  1 , Gabriele Dragoni  1 , Maria Rosa Biagini  1 , Paolo Forte  2 , Andrea Galli  3
Affiliations
Review

Understanding fatigue in primary biliary cholangitis: From pathophysiology to treatment perspectives

Erica Nicola Lynch et al. World J Hepatol. .

Abstract

Fatigue is considered one of the most frequent and debilitating symptoms in primary biliary cholangitis (PBC), affecting over 50% of PBC patients. One in five patients with PBC suffer from severe fatigue, which significantly impairs quality of life. Fatigue is made up of a central and a peripheral component, whose pathophysiology is still greatly unresolved. Central fatigue is characterised by a lack of self-motivation and can manifest both in physical and mental activities (lack of intention). Peripheral fatigue includes neuromuscular dysfunction and muscle weakness (lack of ability). Peripheral fatigue could be explained by an excessive deviation from aerobic to anaerobic metabolism leading to excessive lactic acid accumulation and therefore accelerated decline in muscle function and prolonged recovery time. As opposed to itching, and with the exception of end-stage liver disease, fatigue is not related to disease progression. The objective of this review is to outline current understanding regarding the pathophysiology of fatigue, the role of comorbidities and contributing factors, the main tools for fatigue assessment, the failed therapeutic options, and future treatment perspectives for this disabling symptom. Since fatigue is an extremely common and debilitating symptom and there is still no licensed therapy for fatigue in PBC patients, further research is warranted to understand its causative mechanisms and to find an effective treatment.

Keywords: Central fatigue; Fatigue; Pathophysiology; Peripheral fatigue; Primary biliary cholangitis; Treatment.

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Conflict of interest statement

Conflict-of-interest statement: All authors declare no conflict of interests for this article.

Figures

Figure 1
Figure 1
Fatigue in primary biliary cholangitis: Key concepts. PBC: Primary biliary cholangitis; UDCA: Ursodeoxycholic acid; OCA: Obeticholic acid.
See this image and copyright information in PMC

References

    1. EAftSotLEa , Liver EAftSot. EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol . 2017;67:145–172. - PubMed
    1. Al-Harthy N, Kumagi T, Coltescu C, Hirschfield GM. The specificity of fatigue in primary biliary cirrhosis: evaluation of a large clinic practice. Hepatology . 2010;52:562–570. - PubMed
    1. Hirschfield GM, Dyson JK, Alexander GJM, Chapman MH, CollierJ , Hübscher S, Patanwala I, Pereira SP, Thain C, Thorburn D, Tiniakos D, Walmsley M, Webster G, Jones DEJ. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut . 2018;67:1568–1594. - PMC - PubMed
    1. Shahini E, Ahmed F. Chronic fatigue should not be overlooked in primary biliary cholangitis. J Hepatol . 2021;75:744–745. - PubMed
    1. Montali L, Gragnano A, Miglioretti M, Frigerio A, Vecchio L, Gerussi A, Cristoferi L, Ronca V, D'Amato D, O'Donnell SE, Mancuso C, Lucà M, Yagi M, Reig A, Jopson L, Pilar S, Jones D, Pares A, Mells G, Tanaka A, Carbone M, Invernizzi P. Quality of life in patients with primary biliary cholangitis: A cross-geographical comparison. J Transl Autoimmun . 2021;4:100081. - PMC - PubMed