Chronic fatigue should not be overlooked in primary biliary cholangitis

Shahini, Endrit; Ahmed, Faiza

doi:10.1016/j.jhep.2021.02.020

Cited by 3 publications

(4 citation statements)

References 10 publications

(33 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One in five patients with PBC suffer from severe fatigue, which significantly impairs quality of life[ 3 ]. The severity of chronic fatigue symptoms in PBC predicts liver-related mortality and liver transplantation outcome[ 4 ]. Latitude and sun exposure might influence PBC phenotype, including fatigue status[ 5 ].…”

Section: Introductionmentioning

confidence: 99%

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

Lynch¹,

Campani²,

Innocenti³

et al. 2022

WJH

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

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

Lynch¹,

Campani²,

Innocenti³

et al. 2022

WJH

View full text Add to dashboard Cite

show abstract

“…Patients with PBC can remain clinically asymptomatic for a long time, possibly due to an early and slow-onset disease process [ 4 ]. Extrahepatic autoimmune diseases and hepatobiliary malignant tumours are typically caused by PBC [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

“…Extrahepatic autoimmune diseases and hepatobiliary malignant tumours are typically caused by PBC [ 1 ]. Another important clinical aspect is that although late stages of PBC are temporarily responsive to liver transplantation, between 10.9 and 42.3 percent of patients develop recurrent PBC in the long term, resulting in graft loss and mortality [ 4 ]. Furthermore, as the pathogenesis of chronic fatigue appears to be commonly unrelated to the histological stage of PBC, as well as the degree of hepatic dysfunction or distinct serological markers of autoimmunity [ 4 ], it seems reasonable to take into account pathogenic factors outside the liver, with a key role of immune microenvironment, bone marrow microenvironment, and microbiota–gut mucosal interaction.…”

Section: Introductionmentioning

confidence: 99%

Network Proximity-Based Drug Repurposing Strategy for Early and Late Stages of Primary Biliary Cholangitis

et al. 2022

Self Cite

View full text Add to dashboard Cite

Primary biliary cholangitis (PBC) is a chronic, cholestatic, immune-mediated, and progressive liver disorder. Treatment to preventing the disease from advancing into later and irreversible stages is still an unmet clinical need. Accordingly, we set up a drug repurposing framework to find potential therapeutic agents targeting relevant pathways derived from an expanded pool of genes involved in different stages of PBC. Starting with updated human protein–protein interaction data and genes specifically involved in the early and late stages of PBC, a network medicine approach was used to provide a PBC “proximity” or “involvement” gene ranking using network diffusion algorithms and machine learning models. The top genes in the proximity ranking, when combined with the original PBC-related genes, resulted in a final dataset of the genes most involved in PBC disease. Finally, a drug repurposing strategy was implemented by mining and utilizing dedicated drug–gene interaction and druggable genome information knowledge bases (e.g., the DrugBank repository). We identified several potential drug candidates interacting with PBC pathways after performing an over-representation analysis on our initial 1121-seed gene list and the resulting disease-associated (algorithm-obtained) genes. The mechanism and potential therapeutic applications of such drugs were then thoroughly discussed, with a particular emphasis on different stages of PBC disease. We found that interleukin/EGFR/TNF-alpha inhibitors, branched-chain amino acids, geldanamycin, tauroursodeoxycholic acid, genistein, antioestrogens, curcumin, antineovascularisation agents, enzyme/protease inhibitors, and antirheumatic agents are promising drugs targeting distinct stages of PBC. We developed robust and transparent selection mechanisms for prioritizing already approved medicinal products or investigational products for repurposing based on recognized unmet medical needs in PBC, as well as solid preliminary data to achieve this goal.

show abstract

“…

…”

mentioning

confidence: 99%

Reply to: “Chronic fatigue should not be overlooked in primary biliary cholangitis”

Corpechot

2021

Journal of Hepatology

View full text Add to dashboard Cite

To the Editor:We thank E. Shahini and F. Ahmed for their comments on our study of the long-term impact of preventive ursodeoxycholic acid (UDCA) therapy after liver transplantation for primary biliary cholangitis (PBC). 1,2 To the question "why Corpechot and colleagues did not examine in their work pre-and posttransplant fatigue amongst the various variables?" the answer is quite simple: our study was a non-interventional follow-up study based on retrospectively collected routine care data so that the capture of fatigue, a symptom rarely assessed with standardized validated tools in daily practice, was not feasible. We do not believe that the lack of consideration of this variable in this study could have had a significant influence on its results, specifically secondary outcomes, i.e. graft loss incidence and mortality, since all survival analyses (i.e. both Cox proportionalhazards and restricted mean survival time models) were controlled for the main established prognostic factors and confirmed by the multiple sensitivity analyses done. We do agree that fatigue in PBC is a common but very often under-estimated symptom that significantly impairs quality of life, but from our point of view its real impact on prognosis and more specifically all-cause mortality is questionable and still an open issue.

show abstract

Chronic fatigue should not be overlooked in primary biliary cholangitis

Cited by 3 publications

References 10 publications

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

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

Network Proximity-Based Drug Repurposing Strategy for Early and Late Stages of Primary Biliary Cholangitis

Reply to: “Chronic fatigue should not be overlooked in primary biliary cholangitis”

Contact Info

Product

Resources

About