Novel therapeutic targets in primary biliary cirrhosis

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Novel therapeutic targets in primary biliary cirrhosis. / Dyson, Jessica K; Hirschfield, Gideon M; Adams, David H; Beuers, Ulrich; Mann, Derek A; Lindor, Keith D; Jones, David E J.

In: Nature Reviews. Gastroenterology & Hepatology, Vol. 12, No. 3, 03.2015, p. 147-158.

Research output: Contribution to journalArticle

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Dyson, Jessica K ; Hirschfield, Gideon M ; Adams, David H ; Beuers, Ulrich ; Mann, Derek A ; Lindor, Keith D ; Jones, David E J. / Novel therapeutic targets in primary biliary cirrhosis. In: Nature Reviews. Gastroenterology & Hepatology. 2015 ; Vol. 12, No. 3. pp. 147-158.

Bibtex

@article{fcb3709fc98645b89cfa14975fdd03a9,
title = "Novel therapeutic targets in primary biliary cirrhosis",
abstract = "Primary biliary cirrhosis (PBC) is a chronic immune-mediated liver disease characterized by progressive cholestasis, biliary fibrosis and eventually cirrhosis. It results in characteristic symptoms with marked effects on life quality. The advent of large patient cohorts has challenged the view of PBC as a benign condition treated effectively by the single licensed therapy-ursodeoxycholic acid (UDCA). UDCA nonresponse or under-response has a major bearing on outcome, substantially increasing the likelihood that liver transplantation will be required or that patients will die of the disease. In patients with high-risk, treatment-unresponsive or highly symptomatic disease the need for new treatment approaches is clear. Evolution in our understanding of disease mechanisms is rapidly leading to the advent of new and re-purposed therapeutic agents targeting key processes. Notable opportunities are offered by targeting what could be considered as the 'upstream' immune response, 'midstream' biliary injury and 'downstream' fibrotic processes. Combination therapy targeting several pathways or the development of novel agents addressing multiple components of the disease pathway might be required. Ultimately, PBC therapeutics will require a stratified approach to be adopted in practice. This Review provides a current perspective on potential approaches to PBC treatment, and highlights the challenges faced in evaluating and implementing those treatments.",
keywords = "Cholagogues and Choleretics, Cholestasis, Humans, Liver Cirrhosis, Biliary, Molecular Targeted Therapy, Ursodeoxycholic Acid",
author = "Dyson, {Jessica K} and Hirschfield, {Gideon M} and Adams, {David H} and Ulrich Beuers and Mann, {Derek A} and Lindor, {Keith D} and Jones, {David E J}",
year = "2015",
month = mar,
doi = "10.1038/nrgastro.2015.12",
language = "English",
volume = "12",
pages = "147--158",
journal = "Nature Reviews. Gastroenterology & Hepatology",
issn = "1759-5045",
publisher = "Nature Publishing Group",
number = "3",

}

RIS

TY - JOUR

T1 - Novel therapeutic targets in primary biliary cirrhosis

AU - Dyson, Jessica K

AU - Hirschfield, Gideon M

AU - Adams, David H

AU - Beuers, Ulrich

AU - Mann, Derek A

AU - Lindor, Keith D

AU - Jones, David E J

PY - 2015/3

Y1 - 2015/3

N2 - Primary biliary cirrhosis (PBC) is a chronic immune-mediated liver disease characterized by progressive cholestasis, biliary fibrosis and eventually cirrhosis. It results in characteristic symptoms with marked effects on life quality. The advent of large patient cohorts has challenged the view of PBC as a benign condition treated effectively by the single licensed therapy-ursodeoxycholic acid (UDCA). UDCA nonresponse or under-response has a major bearing on outcome, substantially increasing the likelihood that liver transplantation will be required or that patients will die of the disease. In patients with high-risk, treatment-unresponsive or highly symptomatic disease the need for new treatment approaches is clear. Evolution in our understanding of disease mechanisms is rapidly leading to the advent of new and re-purposed therapeutic agents targeting key processes. Notable opportunities are offered by targeting what could be considered as the 'upstream' immune response, 'midstream' biliary injury and 'downstream' fibrotic processes. Combination therapy targeting several pathways or the development of novel agents addressing multiple components of the disease pathway might be required. Ultimately, PBC therapeutics will require a stratified approach to be adopted in practice. This Review provides a current perspective on potential approaches to PBC treatment, and highlights the challenges faced in evaluating and implementing those treatments.

AB - Primary biliary cirrhosis (PBC) is a chronic immune-mediated liver disease characterized by progressive cholestasis, biliary fibrosis and eventually cirrhosis. It results in characteristic symptoms with marked effects on life quality. The advent of large patient cohorts has challenged the view of PBC as a benign condition treated effectively by the single licensed therapy-ursodeoxycholic acid (UDCA). UDCA nonresponse or under-response has a major bearing on outcome, substantially increasing the likelihood that liver transplantation will be required or that patients will die of the disease. In patients with high-risk, treatment-unresponsive or highly symptomatic disease the need for new treatment approaches is clear. Evolution in our understanding of disease mechanisms is rapidly leading to the advent of new and re-purposed therapeutic agents targeting key processes. Notable opportunities are offered by targeting what could be considered as the 'upstream' immune response, 'midstream' biliary injury and 'downstream' fibrotic processes. Combination therapy targeting several pathways or the development of novel agents addressing multiple components of the disease pathway might be required. Ultimately, PBC therapeutics will require a stratified approach to be adopted in practice. This Review provides a current perspective on potential approaches to PBC treatment, and highlights the challenges faced in evaluating and implementing those treatments.

KW - Cholagogues and Choleretics

KW - Cholestasis

KW - Humans

KW - Liver Cirrhosis, Biliary

KW - Molecular Targeted Therapy

KW - Ursodeoxycholic Acid

U2 - 10.1038/nrgastro.2015.12

DO - 10.1038/nrgastro.2015.12

M3 - Article

C2 - 25645973

VL - 12

SP - 147

EP - 158

JO - Nature Reviews. Gastroenterology & Hepatology

JF - Nature Reviews. Gastroenterology & Hepatology

SN - 1759-5045

IS - 3

ER -