Primary biliary cirrhosis

Hohenester, Simon; Oude-Elferink, Ronald; Beuers, Ulrich

doi:10.1007/s00281-009-0164-5

Cited by 164 publications

(153 citation statements)

References 333 publications

(409 reference statements)

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“…First, our position has always been that the antimitochondrial antibody (AMA) alone is insufficient to make a diagnosis of PBC in either humans or murine models; the diagnosis relies on evidence of autoimmune cholangitis identified on coded slides by a ''blinded'' pathologist. 1 Importantly, cholangitis can be transferred to naive Rag recipients using CD8 T cells from dnTGFbRII mice demonstrating an autoimmune component, data consistent with flow cytometry of liver subpopulations and cytokine analysis. Third, AMA standardization uses not only enzyme-linked immunosorbent assay (ELISA), but also enzyme inhibition, immunoblotting, absorption, peptide microarrays, affinity-purified antisera, and generation of large panels of mAbs, 1 not just the ELISA data of Hohenester et al In fact, the definition and measurement of AMAs always includes reactivity to MIT3, the only recombinant autoantigen approved by the Food and Drug Administration (FDA) for liver autoimmune disease.…”

Section: Replysupporting

confidence: 58%

“…I read with great interest the article by Fontana et al 1 in which the authors demonstrate in mice that aging does not favor or worsen the accumulation of intrahepatic lipids, whereas it promotes hepatocellular injury and inflammation (nonalcoholic steatohepatitis [NASH]), due to the activation of the Fas death pathway and M1 macrophage polarization. The authors used naïve mice aged 830 CORRESPONDENCE HEPATOLOGY, August 2013…”

Section: Old Age and Steatohepatitis: A Dangerous Liaison?mentioning

confidence: 99%

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Antimitochondrial Antibodies May Be Insufficiently Specific to Define Primary Biliary Cirrhosis-Like Disease in Mouse Models

et al. 2013

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Section: Replysupporting

confidence: 58%

Section: Old Age and Steatohepatitis: A Dangerous Liaison?mentioning

confidence: 99%

Antimitochondrial Antibodies May Be Insufficiently Specific to Define Primary Biliary Cirrhosis-Like Disease in Mouse Models

et al. 2013

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“…[17][18][19][20]39,43 Our data may provide a missing pathophysiologic link in the pathogenesis of PBC, which, in our view, is based on the interplay between genetic, exogenous, and endogenous predisposing factors. [17][18][19][20]39,43 Future therapeutic approaches might, therefore, aim to further strengthen the weakened biliary HCO À 3 umbrella in PBC. 7 Advances have been made in understanding the mechanisms and sites of action of ursodeoxycholic acid (UDCA) in the therapy of chronic cholangiopathies.…”

Section: Discussionmentioning

confidence: 79%

“…23 Ischemia-type biliary lesions and nonanastomotic bile duct strictures after liver transplantation with denervation in man 42 may be a consequence of disrupted vagal acetylcholine signaling, a physiologic driving force of biliary HCO À Our data may have particular impact on the understanding of the pathogenesis and treatment of PBC. [17][18][19][20]39,43 Increasing evidence supports the view that cholangiocyte apoptosis is a driving force in the pathogenesis of PBC: It has long been demonstrated that cholangiocyte apoptosis is associated with ductular inflammation in PBC, but not PSC. 44 Furthermore, cholangiocytes of small bile ducts expose immunologically reactive PDC-E2 or PDC-E2-like protein during apoptosis, 16 which might explain, in part, the organ specificity of the immune reaction in PBC.…”

Section: Discussionmentioning

confidence: 93%

A Biliary HCO3 − Umbrella Constitutes A Protective Mechanism Against Bile Acid–Induced Injury in Human Cholangiocytes

et al. 2012

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Human cholangiocytes are continuously exposed to millimolar levels of hydrophobic bile salt monomers. We recently hypothesized that an apical biliary HCO À 3 umbrella might prevent the protonation of biliary glycine-conjugated bile salts and uncontrolled cell entry of the corresponding bile acids, and that defects in this biliary HCO À 3 umbrella might predispose to chronic cholangiopathies. Here, we tested in vitro whether human cholangiocyte integrity in the presence of millimolar bile salt monomers is dependent on (1) pH, (2) adequate expression of the key HCO À 3 exporter, anion exchanger 2 (AE2), and (3) an intact cholangiocyte glycocalyx. To address these questions, human immortalized cholangiocytes and cholangiocarcinoma cells were exposed to chenodeoxycholate and its glycine/taurine conjugates at different pH levels. Bile acid uptake was determined radiochemically. Cell viability and apoptosis were measured enzymatically. AE2 was knocked down by lentiviral short hairpin RNA. A cholangiocyte glycocalyx was identified by electron microscopy, was enzymatically desialylated, and sialylation was quantified by flow cytometry. We found that bile acid uptake and toxicity in human immortalized cholangiocytes and cholangiocarcinoma cell lines in vitro were pH and AE2 dependent, with the highest rates at low pH and when AE2 expression was defective. An apical glycocalyx was identified on cholangiocytes in vitro by electron microscopic techniques. Desialylation of this protective layer increased cholangiocellular vulnerability in a pH-dependent manner. Conclusion: A biliary HCO À 3 umbrella protects human cholangiocytes against damage by bile acid monomers. An intact glycocalyx and adequate AE2 expression are crucial in this process. Defects of the biliary HCO À 3 umbrella may lead to the development of chronic cholangiopathies.

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“…A PBC az 50. életév körül jelentkezik [22,23]. A "tí-pusos" PBC-s betegek 30-65 év közötti nők [2], 25 éves kor alatt ritka [22,23].…”

Section: Klinikai Tünetek Kórjelekunclassified

Review of overlap syndromes of autoimmune liver diseases. Difficulties in the diagnosis and treatment

Hagymási

Tulassay

2013

Orvosi Hetilap

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Az overlap szindróma az autoimmun májbetegségek közötti biokémiai, szerológiai, hisztológiai vagy radiológiai átfedéseket, az autoimmun hepatitis és primer biliaris cirrhosis vagy primer szklerotizáló cholangitis együttes fennállását jelenti. Pontos gyakoriságuk nem ismert, 5-20%-os előfordulásról számolnak be. Az overlap szindrómáknak nincs kórjelző diagnosztikus vizsgálata, a klinikai tünetek, biokémiai, szerológiai, radiológiai és hisztológiai vizsgálatok eredményének együttes értékelésén alapul a kórisme. A domináns megjelenésen alapuló, egyénre szabott, urzodezoxikólsavval végzett és/vagy immunszuppresszív (kortikoszteroid-) kezelést a tapasztalatok, illetve retrospektív, nem randomizált vizsgálatok eredményei alapozzák meg. Orv. Hetil., 2013, 154, 923-929. Kulcsszavak: overlap szindróma, kórisme, kezelés, urzodezoxikólsav, immunszuppresszió Review of overlap syndromes of autoimmune liver diseases Diffi culties in the diagnosis and treatmentOverlap syndromes are biochemical, serological, histological and radiological overlaps across the classic autoimmune liver diseases in the presence of autoimmun hepatitis and primary biliary cirrhosis or primary sclerosing cholangitis. The exact prevalence of the disease is not known, but it may vary between 5% and 20%. Because it has no generally accepted diagnostic criteria, clinical signs, biochemical, serological, radiological and histological fi ndings are evaluated together. Treatment depends on the predominant feature of the overlap syndrome; ursodeoxycholic acid and/or immunsuppressive (corticosteroid) treatment are used, based on observations from retrospective, non-randomized studies. Orv. Hetil., 2013, 154, 923-929. Keywords: overlap syndromes, diagnosis, treatment, ursodeoxycholic acid, immunsuppression (Beérkezett: 2013. április 20.; elfogadva: 2013. május 16.) Rövidítések AIH = autoimmun hepatitis; AiSC = autoimmun szklerotizáló cholangitis; Alba = acetylation lowers binding affi nity; AMA = antimitokrondiális antitest; ANA = antinukleáris antitest; ASGP-R = aszialoglikoprotein-receptor; EASL = European Association for the Study of the Liver; ERCP = endoszkópos retrográd cholangiopancreatographia; IAIHG = International Autoimmune Hepatitis Group; IBD = gyulladásos bélbetegség; MRCP = mágneses rezonanciás cholangiopancreatographia; pANCA = perinukleáris antineutrophil cytoplasmaticus antitest; PBC = primer biliaris cirrhosis; PDC-E2 = piruvát-dehidrogenáz komplex E2 alegysége; PSC = primer szklerotizáló cholangitis; SMA = simaizom-ellenes antitest; UDCA = urzodezoxikólsav Az autoimmun hepatitis (AIH), a primer biliaris cirrhosis (PBC), valamint a primer szklerotizáló cholangitis (PSC) nem pontosan ismert immunfolyamatokkal jellemzett májbetegségek, jellegzetes immunológiai, szerológiai és szövettani eltérésekkel. Ha egy időben két

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Primary biliary cirrhosis

Abstract: Primary biliary cirrhosis

Cited by 164 publications

References 333 publications

Antimitochondrial Antibodies May Be Insufficiently Specific to Define Primary Biliary Cirrhosis-Like Disease in Mouse Models

Antimitochondrial Antibodies May Be Insufficiently Specific to Define Primary Biliary Cirrhosis-Like Disease in Mouse Models

A Biliary HCO3 − Umbrella Constitutes A Protective Mechanism Against Bile Acid–Induced Injury in Human Cholangiocytes

Review of overlap syndromes of autoimmune liver diseases. Difficulties in the diagnosis and treatment

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