Genetics and epigenetics in the pathogenesis of primary biliary cholangitis

Joshita, Satoru; Umemura, Takeji; Tanaka, Eiji; Ôta, Masao

doi:10.1007/s12328-017-0799-z

Cited by 35 publications

(30 citation statements)

References 75 publications

(78 reference statements)

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“…4 Although the etiology of PBC has not yet been elucidated, genetic and environmental factors, along with epigenetic alterations, are suspected. [5][6][7] The vast majority of PBC patients show a favorable response to ursodeoxycholic acid (UDCA), which is currently the most effective treatment for this disease and recommended by many guidelines. [8][9][10] Ursodeoxycholic acid therapy improves liver biochemistry and slows the histologic progression to liver cirrhosis.…”

Section: Introductionmentioning

confidence: 99%

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Biochemical and plasma lipid responses to pemafibrate in patients with primary biliary cholangitis

Joshita

Umemura

Yamashita

et al. 2019

Hepatology Research

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Aim Fibrate addition to ursodeoxycholic acid (UDCA) therapy has been shown to improve both liver biochemistry and long‐term prognosis in primary biliary cholangitis (PBC) patients showing an incomplete biochemical response to UDCA alone. We herein describe the clinical outcome of seven cases of PBC that received the new selective peroxisome proliferator‐activated receptor α modulator, pemafibrate, in combination with UDCA therapy to investigate the biochemical and plasma lipid responses to the drug. Methods Of 124 initially enrolled PBC patients, 12 treated with UDCA alone and seven receiving UDCA plus bezafibrate showed alkaline phosphatase (ALP) levels above the upper limit of normal (330 U/L). Ultimately, seven patients with PBC and dyslipidemia who had agreed to biweekly visits at our hospital for UDCA plus pemafibrate combination therapy were retrospectively analyzed. Results In the four cases that switched from bezafibrate to pemafibrate, ALP became significantly decreased (0.031) and γ‐glutamyltransferase tended to decrease (0.063) over the 3 months following pemafibrate addition. Two patients showed a greater than 50% reduction in ALP. No remarkable differences were observed for plasma lipid levels, alanine aminotransferase, aspartate aminotransferase, or the liver fibrosis marker Mac‐2 binding protein glycosylation isomer between these time points. No adverse drug reactions were recorded. Conclusions Pemafibrate might be another option for PBC patients with an incomplete response to UDCA therapy.

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Section: Introductionmentioning

confidence: 99%

“…The terminology of PBC was changed from primary biliary cirrhosis to more accurately describe the disorder and its natural history . Although the etiology of PBC has not yet been elucidated, genetic and environmental factors, along with epigenetic alterations, are suspected …”

Section: Introductionmentioning

confidence: 99%

Biochemical and plasma lipid responses to pemafibrate in patients with primary biliary cholangitis

Joshita

Umemura

Yamashita

et al. 2019

Hepatology Research

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“…1,2 The precise causes of PBC are not known, but genetic and environmental factors are likely involved and an autoimmune mechanism is implicated in the pathology. 3 Prognosis of PBC is associated with brosis stage, 4,5 which is usually determined by histopathology of liver biopsy specimens. However, histopathological diagnosis using conventional assessment systems (e.g., the Scheuer scoring system 6 ) is associated with sampling errors due to heterogenous intrahepatic changes in PBC.…”

Section: Introductionmentioning

confidence: 99%

Arrival-Time Parametric Imaging in Contrast-Enhanced Ultrasound for Diagnosing Fibrosis in Primary Biliary Cholangitis

Yoshimine

Wakui

Nagai

et al. 2021

Preprint

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Background: To investigate arrival-time parametric imaging (At-PI) in contrast-enhanced ultrasonography (CEUS) for diagnosing fibrosis in primary biliary cholangitis (PBC). Methods: Participants were 48 patients (male/female: 8/40; mean age, 60 ± 13 years) with PBC diagnosed by liver biopsy who underwent CEUS during 2009-2019. Of these, 27 (male/female: 4/23; mean age, 61 ± 13 years) who also underwent shear wave elastography (SWE) were further analyzed. SonazoidTM was intravenously injected and CEUS performed. Contrast dynamics of hepatic segment V and the right kidney were recorded. At-PI were generated from the recorded video clips. Contrast arrival time <5 s was displayed in red, and the ratio of red (ROR) area to the entire liver contrast-enhanced area was calculated. ROR and shear wave velocity (Vs) measured by SWE were compared by fibrosis stage (F0-F3), bile duct loss score, cholangitis activity, hepatitis activity (HA0-HA3), and disease stage (stage 1-4), as determined by liver biopsy.Results: ROR significantly differed between F0 and F2-F3 and between F1 and F2-3. Using ROR to diagnose ³F1 (³F2), area under the receiver operating characteristic curve (AUROC) was 0.77 (0.92) (cutoff, 36.7% [47.1%]; sensitivity, 0.75 [0.92]; specificity, 0.82 [0.81]). Vs significantly differed between F0 and F1, F0 and F2-3, and HA0 and HA1. For diagnosing ³F1 (³F2), Vs had AUROC of 0.84 (0.80) (cutoff, 1.23 m/s [1.40 m/s]; sensitivity, 0.75 [0.60]; specificity, 0.82 [0.86]).Conclusions: At-PI was useful for diagnosing fibrosis, especially F2 or worse, in PBC, suggesting that At-PI can correctly diagnose fibrosis regardless of hepatic inflammation.

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“…PBC is characterized by inflammatory destruction of intrahepatic bile ducts [29,30]. The underlying pathogenic mechanisms are incompletely understood, but genetic and environmental factors as well as epigenetic mechanisms are assumed to be of importance [31]. Large as well as extrahepatic bile ducts are usually spared.…”

Section: Introductionmentioning

confidence: 99%

Autoantibodies associated with primary biliary cholangitis are common among patients with systemic lupus erythematosus even in the absence of elevated liver enzymes

Ahmad

Heijke

Eriksson

et al. 2020

Clinical and Experimental Immunology

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In this study, IgG‐autoantibodies associated with autoimmune hepatitis and primary biliary cholangitis (PBC) were found in a considerable proportion of well‐characterized patients diagnosed with primary Sjögren’s syndrome and systemic lupus erythematosus (SLE) but without known liver involvement or autoimmune liver disease (AILD). PBC‐associated autoantibodies have previously not been reported in a substantial percentage of cases with SLE. However, the association between autoantibody findings and AILD was poor as no significant difference in liver enzymes was observed between AILD‐associated autoantibody negative and positive patients.

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Genetics and epigenetics in the pathogenesis of primary biliary cholangitis

Cited by 35 publications

References 75 publications

Biochemical and plasma lipid responses to pemafibrate in patients with primary biliary cholangitis

Biochemical and plasma lipid responses to pemafibrate in patients with primary biliary cholangitis

Arrival-Time Parametric Imaging in Contrast-Enhanced Ultrasound for Diagnosing Fibrosis in Primary Biliary Cholangitis

Autoantibodies associated with primary biliary cholangitis are common among patients with systemic lupus erythematosus even in the absence of elevated liver enzymes

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