Inflammasome-Driven Fatal Acute-on-Chronic Liver Failure Triggered by Mild COVID-19.

Publication date: Oct 21, 2024

Inflammasome is linked to many inflammatory diseases, including COVID-19 and autoimmune liver diseases. While severe COVID-19 was reported to exacerbate liver failure, we report a fatal acute-on-chronic liver failure (ACLF) in a stable primary biliary cholangitis-autoimmune hepatitis overlap syndrome patient triggered by a mild COVID-19 infection. Postmortem liver biopsy showed sparse SARS-CoV-2-infected macrophages with extensive ASC (apoptosis-associated speck-like protein containing a CARD) speck-positive hepatocytes, correlating with elevated circulating ASC specks and inflammatory cytokines, and depleted blood monocyte subsets, indicating widespread liver inflammasome activation. This first report of a fatal inflammatory cascade in an autoimmune liver disease triggered by a mild remote viral infection hopes to elucidate a less-described pathophysiology of ACLF that could prompt consideration of new diagnostic and therapeutic options.

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Concepts Keywords
Cholangitis Acute-On-Chronic Liver Failure
Liver acute-on-chronic liver failure
Postmortem ASC
Therapeutic autoimmune hepatitis
Viral COVID-19
COVID-19
Cytokines
Cytokines
Fatal Outcome
Female
Hepatitis, Autoimmune
Humans
inflammasome
Inflammasomes
Inflammasomes
Liver
Macrophages
Male
Middle Aged
NLRP3
primary biliary cholangitis
SARS-CoV-2
SARS-CoV-2

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