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SARS-CoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19
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Jnl of Hepatology March 13 2020 - Yijin Wang, Shuhong Liu, Hongyang Liu, Wei Li, Fang Lin, Lina Jiang, Xi Li, Pengfei Xu, Lixin Zhang, Lihua Zhao, Yun Cao, Jiarui Kang, Jianfa Yang, Ling Li, Xiaoyan Liu, Yan Li, Ruifang Nie, Jinsong Mu, Fengmin Lu, Shousong Zhao, Jiangyang Lu, Jingmin Zhao
• Liver enzyme abnormality in COVID-19 patients is associated with disease severity.
• COVID-19 patients with liver enzyme abnormality have higher A-aDO2, higher GGT, lower albumin and decreased circulating CD4+ T cells and B lymphocytes.
• SARS-CoV-2 is able to infect liver and cause conspicuous hepatic cytopathy.
• Massive apoptosis and binuclear hepatocytes were the predominant histological features of SARS-CoV-2 infected liver.

Liver enzyme abnormality is common in patients with coronavirus disease 2019 (COVID-19). Whether or not SARS-CoV-2 infection can lead to liver damage per se remains unknown. Here we reported the clinical characteristics and liver pathological manifestations of COVID-19 patients with liver enzyme abnormality.
We received 156 patients diagnosed of COVID-19 from two designated centers in China, and compared clinical features between patients with elevated aminotransferase or not. Postmortem liver biopsies were obtained from two cases who had elevated aminotransferase. We investigated the patterns of liver impairment by electron microscopy, immunohistochemistry, TUNEL assay, and pathological studies.
64 of 156 (41.0%) COVID-19 patients had elevated aminotransferase. The median levels of ALT were 50 U/L vs. 19 U/L, respectively, AST were 45.5 U/L vs. 24 U/L, respectively in abnormal and normal aminotransferase groups.
The liver enzyme abnormality was associated with disease severity, as well as a series of laboratory tests including higher A-aDO2, higher GGT, lower albumin, decreased CD4+ T cells and B lymphocytes. Ultrastructural examination identified typical coronavirus particles characterized by spike structure in cytoplasm of hepatocytes in two COVID-19 cases. SARS-CoV-2 infected hepatocytes displayed conspicuous mitochondrial swelling, endoplasmic reticulum dilatation, and glycogen granule decrease. Histologically, massive hepatic apoptosis and a certain binuclear hepatocytes were observed. Taken together, both ultrastructural and histological evidence indicated a typical lesion of viral infection. Immunohistochemical results showed scanty CD4+ and CD8+ lymphocytes. No obvious eosinophil infiltration, cholestasis, fibrin deposition, granuloma, massive central necrosis, or interface hepatitis were observed.
SARS-CoV-2 infection in liver is a crucial cause of hepatic impairment in COVID-19 patients. Hence, a surveillance of viral clearance in liver and long outcome of COVID-19 is required.

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