An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs

Consortia, Pbc

doi:10.1016/j.jhep.2021.04.055

Cited by 87 publications

(63 citation statements)

References 35 publications

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“…Despite the unknown aetiology of AILD, genome-wide association studies provided evidence for a strong association of AILD with human leucocyte antigen (HLA) loci, emphasizing a critical role of adaptive T cell responses in the immunopathogenesis of AILD [ 86 , 87 ]. Preclinical studies using TNF neutralisation or Tnfr1 −/− and Tnfr2 −/− mice provided considerable evidence for a pathogenic role of TNF in acute T cell–dependent liver injury [ 27 , 30 , 40 , 88 , 89 ].…”

Section: Role Of Tnf In Autoimmune Liver Disease (Aild)mentioning

confidence: 99%

“…Preclinical studies using TNF neutralisation or Tnfr1 −/− and Tnfr2 −/− mice provided considerable evidence for a pathogenic role of TNF in acute T cell–dependent liver injury [ 27 , 30 , 40 , 88 , 89 ]. Pathway analysis in PBC patients provided evidence for the importance of TNF signalling [ 87 ]. Moreover, few clinical studies reported successful results of anti-TNF treatment in patients with RA and co-existing PBC [ 90 , 91 ].…”

Section: Role Of Tnf In Autoimmune Liver Disease (Aild)mentioning

confidence: 99%

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TNF in the liver: targeting a central player in inflammation

Tiegs

Horst

2022

Semin Immunopathol

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Tumour necrosis factor-α (TNF) is a multifunctional cytokine. First recognized as an endogenous soluble factor that induces necrosis of solid tumours, TNF became increasingly important as pro-inflammatory cytokine being involved in the immunopathogenesis of several autoimmune diseases. In the liver, TNF induces numerous biological responses such as hepatocyte apoptosis and necroptosis, liver inflammation and regeneration, and autoimmunity, but also progression to hepatocellular carcinoma. Considering these multiple functions of TNF in the liver, we propose anti-TNF therapies that specifically target TNF signalling at the level of its specific receptors.

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Section: Role Of Tnf In Autoimmune Liver Disease (Aild)mentioning

confidence: 99%

Section: Role Of Tnf In Autoimmune Liver Disease (Aild)mentioning

confidence: 99%

TNF in the liver: targeting a central player in inflammation

Tiegs

Horst

2022

Semin Immunopathol

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“…Genetic susceptibility and exposure to environmental factors are the two main contributors to PBC development. Genome-wide association studies and observations of identical twins have confirmed genetic associations and risk factors for PBC (66)(67)(68). Molecular mimicry induced by bacterial infection, especially the pyruvate dehydrogenase complex-E2 (PDC-E2), and xenobiotic exposure are important environmental factors that disrupt hepatic immune tolerance and induce PBC (69,70).…”

Section: Regulation Of Immune Response Abnormality By Ppars In Pbcmentioning

confidence: 96%

“…Interleukin-12 (IL-12)-induced Th1 cells produce IFN-γ and IL-2, whereas IL-4 and IL-2-induced Th2 cells secrete a variety of cytokines, including IL-4, IL-10, and IL-13 ( 66 ). Excessive Th1 immune response leads to uncontrolled tissue damage.…”

Section: Regulation Of Immune Response Abnormality By Ppars In Pbcmentioning

confidence: 99%

“…Decreased IL-4 producing CD4 + T cells in patients with advanced PBC also supports this result ( 73 ). In addition, a trans-ethnic genome-wide meta-analysis revealed that IL12RB1 is included in the susceptibility loci of PBC, and Th1 differentiation is significant in pathway analysis ( 66 ). A decrease in liver-infiltrating CD4 + Th1 cells in patients with PBC indicated an adequate response to UDCA treatment ( 74 ).…”

Section: Regulation Of Immune Response Abnormality By Ppars In Pbcmentioning

confidence: 99%

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Peroxisome Proliferator-Activated Receptors Regulate Hepatic Immunity and Assist in the Treatment of Primary Biliary Cholangitis

et al. 2022

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Fibrates, which are agonists of peroxisome proliferator-activated receptor alpha, have received increasing attention in the treatment of primary biliary cholangitis. Reduced alkaline phosphatase levels and improved clinical outcomes were observed in patients with primary biliary cholangitis with an inadequate response to ursodeoxycholic acid (UDCA) monotherapy4 when treated with bezafibrate or fenofibrate combined with UDCA. In contrast to obeticholic acid, which exacerbates pruritus in patients, fibrates have been shown to relieve pruritus. Clinical trial outcomes show potential for the treatment of primary biliary cholangitis by targeting peroxisome proliferator-activated receptors. It is currently agreed that primary biliary cholangitis is an autoimmune-mediated cholestatic liver disease, and peroxisome proliferator-activated receptor is a nuclear receptor that regulates the functions of multiple immune cells, thus playing an important role in regulating innate and adaptive immunity. Therefore, this review focuses on the immune disorder of primary biliary cholangitis and summarizes the regulation of hepatic immunity when peroxisome proliferator-activated receptors are targeted for treating primary biliary cholangitis.

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Depressive symptom as a risk factor for cirrhosis in patients with primary biliary cholangitis: Analysis based on Lasso‐logistic regression and decision tree models

Zhou,

Li,

Liu

et al. 2024

Brain and Behavior

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BackgroundDepressive symptoms are frequently observed in patients with primary biliary cholangitis (PBC). The role of depressive symptoms on cirrhosis has not been fully noticed in PBC. We aimed to establish a risk model for cirrhosis that took depressive symptoms into account.MethodsDepressive symptoms were assessed by the 17‐item Hamilton Depression Rating Scale (HAMD‐17). HAMD‐17 score was analyzed in relation to clinical parameters. Least absolute shrinkage and selection operator (Lasso)‐logistic regression and decision tree models were used to explore the effect of depressive symptoms on cirrhosis.ResultsThe rate of depressive symptom in patients with PBC (n = 162) was higher than in healthy controls (n = 180) (52.5% vs. 16.1%; p < .001). HAMD‐17 score was negatively associated with C4 levels and positively associated with levels of alkaline phosphatase (ALP), γ‐glutamyl transpeptidase (GGT), total bilirubin (TB), Immunoglobulin (Ig) G, and IgM (r = −0.162, 0.197, 0.355, 0.203, 0.182, 0.314, p < .05). In Lasso‐logistic regression analysis, HAMD‐17 score, human leukocyte antigen (HLA)‐DRB1*03:01 allele, age, ALP levels, and IgM levels (odds ratio [OR] = 1.087, 7.353, 1.075, 1.009, 1.005; p < 0.05) were independent risk factors for cirrhosis. Elevated HAMD‐17 score was also a discriminating factor for high risk of cirrhosis in patients with PBC in decision tree model.ConclusionsDepressive symptoms were associated with disease severity. Elevated HAMD‐17 score was a risk factor for cirrhosis in patients with PBC.

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An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs

Cited by 87 publications

References 35 publications

TNF in the liver: targeting a central player in inflammation

TNF in the liver: targeting a central player in inflammation

Peroxisome Proliferator-Activated Receptors Regulate Hepatic Immunity and Assist in the Treatment of Primary Biliary Cholangitis

Depressive symptom as a risk factor for cirrhosis in patients with primary biliary cholangitis: Analysis based on Lasso‐logistic regression and decision tree models

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