Inflammation: Cause or consequence of chronic cholestatic liver injury

Cholestasis is a result of obstruction of the biliary tracts. It is a common cause of liver pathology after exposure to toxic xenobiotics and during numerous other liver diseases. Accumulation of bile acids in the liver is thought to be a major driver of liver injury during cholestasis and can lead...

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Bibliographic Details
Published in:Food and chemical toxicology 2020-03, Vol.137, p.111133, Article 111133
Main Author: Woolbright, Benjamin L.
Format: Article
Language:English
Subjects:
Apoptosis
B-Cell
Bile acid
Biliary atresia
Neutrophil
Primary biliary cholangitis
Primary sclerosing cholangitis
T-cell
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Summary:Cholestasis is a result of obstruction of the biliary tracts. It is a common cause of liver pathology after exposure to toxic xenobiotics and during numerous other liver diseases. Accumulation of bile acids in the liver is thought to be a major driver of liver injury during cholestasis and can lead to eventual liver fibrosis and cirrhosis. As such, current therapy in the field of chronic liver diseases with prominent cholestasis relies heavily on increasing choleresis to limit accumulation of bile acids. Many of these same diseases also present with autoimmunity before the onset of cholestasis though, indicating the inflammation may be an initiating component of the pathology. Moreover, cytotoxic inflammatory mediators accumulate during cholestasis and can propagate liver injury. Anti-inflammatory biologics and small molecules have largely failed clinical trials in these diseases though and as such, targeting inflammation as a means to address cholestatic liver injury remains debatable. The purpose of this review is to understand the different roles that inflammation can play during cholestatic liver injury and attempt to define how new therapeutic targets that limit or control inflammation may be beneficial for patients with chronic cholestatic liver disease. •Pathological and xenobiotic induced cholestasis remain major problems.•Accumulation of bile acids provokes liver injury which enhances inflammation.•Autoimmune cholestasis is precipitated by biliary inflammation.•Inflammation remains a major drug target in cholestasis.•Novel studies are needed to identify critical inflammatory mediators in patients.
ISSN:0278-6915
1873-6351
DOI:10.1016/j.fct.2020.111133