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

• Published in: Viruses Vol. 16; no. 10; p. 1646
• Main Authors: Chen, Vivian Chih-Wei, Joseph, Craig Ryan, Chan, Wharton O Y, Sia, Wan Rong, Su, Qi, Sam, Xin Xiu, Tamilarasan, Hemavathi, Mah, Yun Yan, Ng, Wei Lun, Yeong, Joe, Wang, Lin-Fa, Krishnamoorthy, Thinesh L, Leow, Wei-Qiang, Ahn, Matae, Chow, Wan Cheng
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.10.2024; MDPI
• Subjects: 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; 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; Singapore; United States > US; COVID-19; ASC; SARS-CoV-2; autoimmune hepatitis; inflammasome; NLRP3; primary biliary cholangitis; acute-on-chronic liver failure
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v16101646

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.