Role of ductular reaction and ductular-canalicular junctions in identifying severe primary biliary cholangitis.
AE2, anion exchanger 2
ALP, alkaline phosphatase
ALPt0, ALP at diagnosis
ALPt12, ALP at 12 months after UDCA therapy
ALT, alanine aminotransferase
ALTt0, ALT at diagnosis
AMA, antimitochondrial antibody
ANA, antinuclear antibody
AST, aspartate aminotransferase
ASTt0, AST at diagnosis
BAC, bile acid control
BIL, bilirubin
BILt0, BIL at diagnosis
CA, cholangitis activity
CK19, cytokeratin 19
CK7, cytokeratin 7
Cholangiopathy
Cholestasis
DCJ, ductular–canalicular junction
DCJ/d, DCJ per ductule
DCJ/pt, DCJ per portal tract
DR, ductular reaction
EpCAM, epithelial cell adhesion molecule
GGT, gamma-glutamyl transferase
HA, hepatitis activity
HSC, hepatic stellate cell
Histology
IH, intermediate hepatocyte
Liver biopsy
MF, myofibroblast
Muc-1, mucin 1
PBC, primary biliary cholangitis
PCNA, proliferating cell nuclear antigen
RT-qPCR, real-time quantitative PCR
Regeneration
SCTR, secretin receptor
SQ, semiquantitative
UDCA, ursodeoxycholic acid
ULN, upper limit of normal
URS, UDCA response score
Ursodeoxycholic acid
WT, wild type
αSMA, α-smooth muscle actin
Journal
JHEP reports : innovation in hepatology
ISSN: 2589-5559
Titre abrégé: JHEP Rep
Pays: Netherlands
ID NLM: 101761237
Informations de publication
Date de publication:
Nov 2022
Nov 2022
Historique:
received:
17
02
2022
revised:
21
07
2022
accepted:
03
08
2022
entrez:
21
10
2022
pubmed:
22
10
2022
medline:
22
10
2022
Statut:
epublish
Résumé
Primary biliary cholangitis (PBC) is a chronic cholangiopathy characterised by immuno-mediated injury of interlobular bile ducts leading to intrahepatic cholestasis and progressive liver fibrosis. PBC histology is characterised by portal inflammation, progressive fibrosis, ductopenia, and the appearance of the so-called ductular reaction. The aim of the present study was to investigate the pathogenetic relevance of ductular reaction in PBC. Liver biopsies were collected from naïve people with PBC (N = 87). Clinical-serological parameters were obtained at diagnosis and after 1 year of ursodeoxycholic acid (UDCA) treatment. Histological staging was performed on all slides according to multiple scoring systems and criteria for PBC. Liver samples were obtained from Ductular reaction in people with PBC correlated with the disease stage and liver fibrosis, but not with disease activity; an extensive ductular reaction correlated with serum alkaline phosphatase levels at diagnosis, response to UDCA, and individuals' estimated survival, independently from other histological parameters, including disease stage. In people with PBC, reactive ductules were associated with the establishment of junctions with bile canaliculi and with fibrogenetic cell activation. Consistently, in a mouse model of intrahepatic cholestasis, UDCA treatment was effective in reducing ductular reaction and fibrosis and increasing ductular-canalicular junctions. Extensive ductular reaction outlines a severe histologic phenotype in PBC and is associated with an inadequate therapy response and a worse estimated prognosis. In people affected by primary biliary cholangitis (PBC), the histological appearance of extensive ductular reaction identifies individuals at risk of progressive fibrosis. Ductular reaction at diagnosis correlates with the lack of response to first-line therapy with ursodeoxycholic acid and serves to restore ductular-canalicular junctions in people with PBC. Assessing ductular reaction extension at diagnosis may add valuable information for clinicians.
Sections du résumé
Background & Aims
UNASSIGNED
Primary biliary cholangitis (PBC) is a chronic cholangiopathy characterised by immuno-mediated injury of interlobular bile ducts leading to intrahepatic cholestasis and progressive liver fibrosis. PBC histology is characterised by portal inflammation, progressive fibrosis, ductopenia, and the appearance of the so-called ductular reaction. The aim of the present study was to investigate the pathogenetic relevance of ductular reaction in PBC.
Methods
UNASSIGNED
Liver biopsies were collected from naïve people with PBC (N = 87). Clinical-serological parameters were obtained at diagnosis and after 1 year of ursodeoxycholic acid (UDCA) treatment. Histological staging was performed on all slides according to multiple scoring systems and criteria for PBC. Liver samples were obtained from
Results
UNASSIGNED
Ductular reaction in people with PBC correlated with the disease stage and liver fibrosis, but not with disease activity; an extensive ductular reaction correlated with serum alkaline phosphatase levels at diagnosis, response to UDCA, and individuals' estimated survival, independently from other histological parameters, including disease stage. In people with PBC, reactive ductules were associated with the establishment of junctions with bile canaliculi and with fibrogenetic cell activation. Consistently, in a mouse model of intrahepatic cholestasis, UDCA treatment was effective in reducing ductular reaction and fibrosis and increasing ductular-canalicular junctions.
Conclusions
UNASSIGNED
Extensive ductular reaction outlines a severe histologic phenotype in PBC and is associated with an inadequate therapy response and a worse estimated prognosis.
Lay summary
UNASSIGNED
In people affected by primary biliary cholangitis (PBC), the histological appearance of extensive ductular reaction identifies individuals at risk of progressive fibrosis. Ductular reaction at diagnosis correlates with the lack of response to first-line therapy with ursodeoxycholic acid and serves to restore ductular-canalicular junctions in people with PBC. Assessing ductular reaction extension at diagnosis may add valuable information for clinicians.
Identifiants
pubmed: 36267871
doi: 10.1016/j.jhepr.2022.100556
pii: S2589-5559(22)00128-8
pmc: PMC9576897
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100556Subventions
Organisme : BLRD VA
ID : I01 BX000574
Pays : United States
Organisme : BLRD VA
ID : IK6 BX004601
Pays : United States
Informations de copyright
© 2022 The Author(s).
Déclaration de conflit d'intérêts
The authors declare that there is no conflict of interest. Please refer to the accompanying ICMJE disclosure forms for further details.
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