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

by Ng, Wei Lun , Ahn, Matae , Yeong, Joe , Leow, Wei-Qiang , Su, Qi , Krishnamoorthy, Thinesh L. , Joseph, Craig Ryan , Wang, Lin-Fa , Sam, Xin Xiu , Mah, Yun Yan , Tamilarasan, Hemavathi , Chow, Wan Cheng , Chen, Vivian Chih-Wei , Chan, Wharton O. Y. , Sia, Wan Rong

in Acute-On-Chronic Liver Failure - etiology / Acute-On-Chronic Liver Failure - virology / Antibodies / Apoptosis / ASC / Ascites / Biopsy / Case Report / Cell activation / Cholangitis / Chronic infection / COVID-19 / COVID-19 - complications / COVID-19 - immunology / COVID-19 - pathology / Cytokines / Cytokines - metabolism / Diagnosis / Diuretics / Fatal Outcome / Female / Hemorrhage / Hepatitis / Hepatitis, Autoimmune - pathology / Hepatocytes / Humans / Hypertension / Illnesses / Immunohistochemistry / inflammasome / Inflammasomes / Inflammasomes - metabolism / Inflammatory diseases / Liver - pathology / Liver - virology / Liver diseases / Liver failure / Macrophages / Macrophages - immunology / Male / Middle Aged / Monocytes / NLRP3 / Pathophysiology / Patient admissions / primary biliary cholangitis / Risk factors / SARS-CoV-2 / Severe acute respiratory syndrome coronavirus 2 / Software / Viral infections

2024

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2024

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2024

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Journal Article

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

Ng, Wei Lun,

Ahn, Matae,

Yeong, Joe,

Leow, Wei-Qiang,

Su, Qi,

Krishnamoorthy, Thinesh L.,

Joseph, Craig Ryan,

Wang, Lin-Fa,

Sam, Xin Xiu,

Mah, Yun Yan,

Tamilarasan, Hemavathi,

Chow, Wan Cheng,

Chen, Vivian Chih-Wei,

Chan, Wharton O. Y.,

Sia, Wan Rong

2024

Overview

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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Publisher

MDPI AG,MDPI

Subject

Acute-On-Chronic Liver Failure - etiology

/ Acute-On-Chronic Liver Failure - virology

/ Antibodies

/ Apoptosis

/ ASC

/ Ascites

/ Biopsy