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A Mouse Model of Chronic Liver Fibrosis for the Study of Biliary Atresia

A Mouse Model of Chronic Liver Fibrosis for the Study of Biliary Atresia

Published on: February 3, 2023

CD14 is associated with biliary stricture formation.

Kilian Friedrich¹, Mark Smit¹, Maik Brune²

¹Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg, Germany.

Hepatology (Baltimore, Md.)

|March 13, 2016

Summary

This summary is machine-generated.

The CD14 gene variant influences biliary stricture risk in primary sclerosing cholangitis (PSC) and liver transplant (LTx) patients. TT genotype offers protection against strictures and infection, impacting patient survival.

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Area of Science:

Immunology
Gastroenterology
Genetics

Background:

The exact causes of biliary stricture in primary sclerosing cholangitis (PSC) and post-liver transplantation (LTx) are unknown.
CD14 receptor signaling, part of the innate immune system, has a known genetic variant linked to alcoholic liver disease.

Purpose of the Study:

To investigate the association between the CD14 -260C>T genetic polymorphism and the development of biliary strictures in PSC and LTx patients.
To explore the role of CD14 signaling in innate immunity, bacterial infection, and clinical outcomes in these patient cohorts.

Main Methods:

Genotyping of the CD14 -260C>T (rs2569190) polymorphism in PSC, LTx, and primary biliary cirrhosis (PBC) patients.
Correlation of genotypes with clinical outcomes, including stricture formation and survival.
Screening of biliary tissue, bile, and blood for innate immune markers and bacterial infection markers.

Main Results:

The CD14 -260C>T genotype was linked to dominant bile duct stricture development in PSC patients (P = 0.02).
TT genotype carriers in the LTx cohort showed protection against nonanastomotic biliary strictures (4.1% vs. 12.6%, P = 0.01).
Upregulation of chemokine ligand 8 and receptor 6 in PSC patients with TT genotype; TT genotype protected PSC patients from Gram-negative bacterial infection (P = 0.02).
Serum-soluble CD14 levels correlated with genotype and served as an independent predictor of survival in PSC patients (HR, 0.40; P = 0.01).

Conclusions:

CD14-mediated innate immune responses are vital in biliary infection and stricture formation.
The CD14 -260C>T polymorphism influences susceptibility to biliary strictures and infections in PSC and LTx.
Targeting CD14 signaling pathways may offer therapeutic benefits and warrants further investigation.