The Pathogenesis of Primary Biliary Cholangitis: A Comprehensive Review

Lleo, Ana; Leung, Patrick S.C.; Hirschfield, Gideon; Gershwin, Eric

doi:10.1055/s-0039-1697617

Cited by 100 publications

(89 citation statements)

References 225 publications

(211 reference statements)

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“…Criteria. Studies were included if they met the following criteria: (1) the study was original research; (2) the study reported a prevalence or incidence (or it reported raw data that allowed the calculation of estimates); (3) the study was conducted in Europe; and (4) the study was published in 2000 or later.…”

Section: Inclusion and Exclusionmentioning

confidence: 99%

“…Exclusion criteria for the meta-analysis were as follows: (1) the study was a review article; (2) the study was a genome study or an animal study; (3) the study described the epidemiology of PBC among hospitalized patients; and (4) the study did not specifically describe patients with PBC.…”

Section: Inclusion and Exclusionmentioning

confidence: 99%

“…Primary biliary cholangitis (PBC) is a chronic inflammatory autoimmune cholestatic liver disease [ 1 ]. The aetiology of PBC remains unknown; however, PBC is associated with a myriad of both HLA and non-HLA genes as well as with several environmental factors (socioeconomic status, infectious agents, environmental pollutants, vitamin D, nutrition, drugs, and physical and psychological stresses) [ 2 ]. An increased prevalence of PBC has been associated with proximity to waste disposal sites [ 3 , 4 ], and in the past, it has also been associated with a north-south latitudinal gradient [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

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The Epidemiology of Primary Biliary Cholangitis in European Countries: A Systematic Review and Meta-Analysis

Gazda

Dražilová

Janíčko

et al. 2021

Canadian Journal of Gastroenterology and Hepatology

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Background. Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease with wide ranges of reported incidence and prevalence. Aim. To map the incidence and prevalence of PBC in European countries from 2000 through 2020. Methods. Following PRISMA recommendations, we searched the Medline and Scopus databases for studies with information on either the incidence or prevalence of PBC. After data extraction, we used a random-effects model to estimate both the pooled annual incidence rate and pooled point-prevalence rate and performed subgroup analyses to identify components contributing to between-study heterogeneity. Results. We performed a qualitative and quantitative analysis of 18 studies. The pooled point-prevalence rate was 22.27 cases per 100,000 inhabitants (95% CI: 17.98–27.01), and the pooled annual incidence rate was 1.87 new cases per 100,000 inhabitants (95% CI: 1.46–2.34). In the subgroup analyses, we proved that a small part of the between-study heterogeneity is significantly associated with a history of being part of the Eastern Bloc.

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Section: Inclusion and Exclusionmentioning

confidence: 99%

Section: Inclusion and Exclusionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Epidemiology of Primary Biliary Cholangitis in European Countries: A Systematic Review and Meta-Analysis

Gazda

Dražilová

Janíčko

et al. 2021

Canadian Journal of Gastroenterology and Hepatology

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“…Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease characterized by nonsuppurative inflammatory destruction of the interlobular bile ducts [ 143 ]. It is well established that cholestasis causes Cu accumulation in the liver.…”

Section: The Roles Of Trace Elementsmentioning

confidence: 99%

Current Trends of Essential Trace Elements in Patients with Chronic Liver Diseases

Himoto

Masaki

2020

Nutrients

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Essential trace elements play crucial roles in the maintenance of health, since they are involved in many metabolic pathways. A deficiency or an excess of some trace elements, including zinc, selenium, iron, and copper, frequently causes these metabolic disorders such as impaired glucose tolerance and dyslipidemia. The liver largely regulates most of the metabolism of trace elements, and accordingly, an impairment of liver functions can result in numerous metabolic disorders. The administration or depletion of these trace elements can improve such metabolic disorders and liver dysfunction. Recent advances in molecular biological techniques have helped to elucidate the putative mechanisms by which liver disorders evoke metabolic abnormalities that are due to deficiencies or excesses of these trace elements. A genome-wide association study revealed that a genetic polymorphism affected the metabolism of a specific trace element. Gut dysbiosis was also responsible for impairment of the metabolism of a trace element. This review focuses on the current trends of four trace elements in chronic liver diseases, including chronic hepatitis, liver cirrhosis, nonalcoholic fatty liver disease, and autoimmune liver diseases. The novel mechanisms by which the trace elements participated in the pathogenesis of the chronic liver diseases are also mentioned.

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“…Primary Biliary Cholangitis (PBC) is a chronic cholestatic liver disease characterized by progressive destruction of the intrahepatic bile ducts, leading to cholestasis, portal inflammation, fibrosis and potentially cirrhosis and liver failure (1). Mononuclear phagocytes (MNPs) are myeloid immune cells comprised of monocytes, macrophages (MFs) and dendritic cells (DCs).…”

Section: Introductionmentioning

confidence: 99%

Interleukin 23 Produced by Hepatic Monocyte-Derived Macrophages Is Essential for the Development of Murine Primary Biliary Cholangitis

et al. 2021

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Background and AimsPrimary Biliary Cholangitis (PBC) is an organ-specific autoimmune liver disease. Mononuclear phagocytes (MNPs), comprise of monocyte, dendritic cells and monocyte-derived macrophages, constitute major arm of the innate immune system known to be involved in the pathogenesis of autoimmune disorders. MNPs were shown to accumulate around intra-hepatic bile ducts in livers of PBC patients. Interleukin 23 (IL-23) is a pro-inflammatory cytokine. IL-23-positive cells were detected in livers of patients with advanced stage PBC and IL-23 serum levels found to be in correlation with PBC disease severity. Our overall goal was to assess the importance of IL-23 derived from MNPs in PBC pathogenesis.MethodsWe utilized an inducible murine model of PBC and took advantage of transgenic mice targeting expression of IL-23 by specific MNP populations. Analysis included liver histology assessment, flow cytometry of hepatic immune cells and hepatic cytokine profile evaluation. Specific MNPs sub-populations were sorted and assessed for IL-23 expression levels.ResultsFlow cytometry analysis of non-parenchymal liver cells in autoimmune cholangitis revealed massive infiltration of the liver by MNPs and neutrophils and a decrease in Kupffer cells numbers. In addition, a 4-fold increase in the incidence of hepatic IL-17A producing CD4+ T cells was found to be associated with an increase in hepatic IL23-p19 and IL17A expression levels. Disease severity was significantly ameliorated in both CD11ccreP19flox/flox and CX3CR1creP19 flox/flox mice as assessed by reduced portal inflammation and decreased hepatic expression of various inflammatory cytokines. Amelioration of disease severity was associated with reduction in IL-17A producing CD4+ T cells percentages and decreased hepatic IL23-p19 and IL17A expression levels. qRT-PCR analysis of sorted hepatic MNPs demonstrated high expression levels of IL-23 mRNA specifically by CX3CR1hiCD11c+ monocyte-derived macrophages.ConclusionOur results indicate a major role for IL-23 produced by hepatic monocyte-derived macrophages in the pathogenesis of PBC. These results may pave the road for the development of new immune-based and cell specific therapeutic modalities for PBC patients not responding to current therapies.

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The Pathogenesis of Primary Biliary Cholangitis: A Comprehensive Review

Cited by 100 publications

References 225 publications

The Epidemiology of Primary Biliary Cholangitis in European Countries: A Systematic Review and Meta-Analysis

The Epidemiology of Primary Biliary Cholangitis in European Countries: A Systematic Review and Meta-Analysis

Current Trends of Essential Trace Elements in Patients with Chronic Liver Diseases

Interleukin 23 Produced by Hepatic Monocyte-Derived Macrophages Is Essential for the Development of Murine Primary Biliary Cholangitis

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