Primary Sclerosing Cholangitis: Is Any Treatment Worthwhile?

Barnabas, Ashley; Chapman, Roger W.

doi:10.1007/s11894-011-0230-8

Cited by 16 publications

(13 citation statements)

References 56 publications

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“…Despite the efficacy of ursodeoxycholic acid in PBC and corticosteroids in AIH, a considerable fraction of these patients, as well as those with PSC, still develop progressive liver fibrosis as demonstrated by the significant proportion who advance to end-stage liver disease and require liver transplantation (autoimmune liver diseases comprising approximately 10% of the overall European liver transplant program) [10][11][12] . The limited efficacy of immunosuppressive treatments in PBC and PSC is paradoxical, given that both exhibit several prototypical features of autoimmunity, a fact for which the underlying mechanisms are so far unknown.…”

Section: Introductionmentioning

confidence: 99%

Genetic Risk and the Development of Autoimmune Liver Disease

Karlsen¹,

Chung

2015

Dig Dis

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Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) have collectively been recognized as autoimmune liver diseases. They have all been subjected to genome-wide association studies (GWAS) and several dozens susceptibility loci have been determined. The predominant feature of the genetic findings is that of a strong association with the human leukocyte antigen (HLA) and numerous weak associations scattered throughout the remainder of the genome. The non-HLA associations show some degree of overlap, not only between PBC, PSC and AIH, but also with other autoimmune and immune-mediated diseases. Mathematical modelling shows that the main fraction of autoimmune disease risk (including that of autoimmune liver diseases) is not explained by GWAS, proposing a major role of environmental factors. The HLA associations and autoantibodies observed in these conditions may hold clues as to the nature of such factors, which are exceedingly difficult to map by means of epidemiological study designs. The present review article explores the potential relationship between genetic risk as determined by GWAS and environmental risk in autoimmune liver diseases, and proposes a model for relevant thinking on the susceptibility genes in PBC, PSC and AIH.

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Section: Introductionmentioning

confidence: 99%

Genetic Risk and the Development of Autoimmune Liver Disease

Karlsen¹,

Chung

2015

Dig Dis

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“…Ursodeoxycholic acid (UDCA) at a dosage of 15-20 mg/kg/day is usually well tolerated and improves liver biochemistry without clear survival benefit [18] , but it is important to avoid higher doses, which have been shown to be associated with adverse outcomes [19] . Notably, even the so far largest PSC drug trial recruiting 219 patients was still underpowered and did not reach the calculated sample size of 346 [20] .…”

Section: Therapy Of Psc -Todaymentioning

confidence: 99%

Therapy of Primary Sclerosing Cholangitis - Today and Tomorrow

Halilbasic

Fuchs

Hofer

et al. 2015

Dig Dis

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Primary sclerosing cholangitis (PSC) represents a fibro-obliterative bile duct disease with unpredictable individual clinical course that may progress to liver cirrhosis and malignancy. Due to our incomplete understanding of the etiology and pathogenesis of this disease, the therapeutic options are still rather limited. Bile acids play a key role in mediating cholangiocellular and hepatocellular injury in cholangiopathies such as PSC. Therefore, strategies targeting bile composition and homeostasis are valid approaches in PSC. Ursodeoxycholic acid (UDCA) is the paradigm therapeutic bile acid and its role in medical therapy of PSC is still under debate. Promising novel bile acid-based therapeutic options include 24-norursodeoxycholic acid (norUDCA), a side chain-shortened C₂₃ homologue of UDCA, and bile acid receptor/farnesoid X receptor agonists (e.g. obeticholic acid). Other nuclear receptors such as fatty acid-activated peroxisome proliferator-activated receptors, vitamin D receptor and vitamin A receptors (retinoic acid receptor, retinoid X receptor) are also of potential interest and can be targeted by already available drugs. Furthermore, drugs targeting the gut-liver axis (e.g. intregrin blockers such as vedolizumab, antibiotics) appear promising, based on the close link of PSC to inflammatory bowel disease and the emerging relevance of the gut microbiome for the development of PSC. Finally, fibrosis represents a valid therapeutic target for anti-fibrotic drugs (e.g. simtuzumab) in PSC as paradigm fibro-obliterative disease. This review summarizes the current status and recent progress in the development of targeted therapeutic approaches based on increasing knowledge about the pathogenesis of this disease.

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“…Bei Patienten mit CU und PSC wurde sogar ein erhöhtes Risiko für die Entwicklung einer kolorektalen Neoplasie nach hochdosierter UDCA-Therapie nachgewiesen [33]. Auch der PCS-Verlauf scheint unter einer Hochdosistherapie mit UDCA ungünstiger zu sein [34].…”

Section: Epidemiologieunclassified

“…Eine endoskopische Therapie von dominanten Strikturen kann den langfristi-gen Verlauf positiv beeinflussen. Durch eine orthotope Lebertransplantation wird ein gutes Outcome bei Patienten mit einer PSC im Endstadium ermöglicht [34].…”

Section: Epidemiologieunclassified

Therapie der extraintestinalen CED-Manifestationen

Zeitz¹,

Vavricka

2014

coloproctology

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Morbus Crohn und Colitis ulcerosa sind chronisch-entzündliche Darmerkrankungen (CED), die nicht auf das Gastrointestinalsystem beschränkt sind. Zusätzlich können diverse Organsysteme mit betroffen sein, was die CED zu einer Systemerkrankung macht. Die häufigsten extraintestinalen Manifestationen beinhalten muskuloskelettale, ophthalmologische, dermatologische und hepatobiliäre Erkrankungen, obwohl prinzipiell jedes Organsystem betroffen sein kann. Sie können signifikant zur Morbidität von CED-Patienten beitragen und die Lebensqualität deutlich einschränken. Die Betreuung sollte aufgrund der Vielfalt der betroffenen Organsysteme interdisziplinär durch ein in der CED-Behandlung geschultes medizinisches Personal erfolgen. Ein frühes Erkennen von extraintestinalen Manifestationen ermöglicht eine gezielte Therapie und verringert die Gesamtmorbidität der betroffenen Patienten. Insbesondere kann eine effektive Erhaltungstherapie das Auftreten von Manifestationen, die eng mit der Krankheitsaktivität der zugrunde liegenden CED verknüpft sind, vermeiden helfen. Neben spezifischen Interventionen, die nicht mit der Krankheitsaktivität der CED verknüpft sind, spielt eine antiinflammatorische oder immunmodulatorische Therapie eine entscheidende Rolle. Zudem gewinnt die Verwendung einer TNF-Hemmer-Therapie in der Behandlung von verschiedenen extraintestinalen Manifestationen zunehmend an Bedeutung.

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Primary Sclerosing Cholangitis: Is Any Treatment Worthwhile?

Cited by 16 publications

References 56 publications

Genetic Risk and the Development of Autoimmune Liver Disease

Genetic Risk and the Development of Autoimmune Liver Disease

Therapy of Primary Sclerosing Cholangitis - Today and Tomorrow

Therapie der extraintestinalen CED-Manifestationen

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