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World J Hepatol. Jun 27, 2022; 14(6): 1111-1119
Published online Jun 27, 2022. doi: 10.4254/wjh.v14.i6.1111
Understanding fatigue in primary biliary cholangitis: From pathophysiology to treatment perspectives
Erica Nicola Lynch, Claudia Campani, Tommaso Innocenti, Gabriele Dragoni, Maria Rosa Biagini, Paolo Forte, Andrea Galli
Erica Nicola Lynch, Claudia Campani, Tommaso Innocenti, Gabriele Dragoni, Maria Rosa Biagini, Andrea Galli, Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
Claudia Campani, Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
Gabriele Dragoni, Department of Medical Biotechnologies, University of Siena, Siena 53100, Italy
Paolo Forte, Division of Gastroenterology, University Hospital “Careggi”, Florence 50134, Italy
Author contributions: Lynch EN and Campani C wrote the paper; Lynch EN (native English speaker) performed English language proofreading; Innocenti T, Dragoni G, Biagini M R, Forte P, and Galli A critically revised the manuscript; and all authors approved the final version of the paper.
Conflict-of-interest statement: All authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Andrea Galli, MD, PhD, Professor, Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Viale GB Morgagni 50, Florence 50134, Italy. andrea.galli@unifi.it
Received: January 26, 2022
Peer-review started: January 26, 2022
First decision: April 8, 2022
Revised: April 18, 2022
Accepted: May 28, 2022
Article in press: May 28, 2022
Published online: June 27, 2022
Processing time: 148 Days and 4.3 Hours
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: Fatigue; Primary biliary cholangitis; Treatment; Pathophysiology; Central fatigue; Peripheral fatigue

Core Tip: Fatigue is considered one of the most frequent and debilitating symptoms in primary biliary cholangitis, affecting over 50% of patients. 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 effective treatment.