SARS-CoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19


      • Liver enzyme abnormalities in patients with COVID-19 are associated with disease severity.
      • Patients with liver enzyme abnormalities have higher A-aDO2 and GGT, lower albumin and decreased circulating CD4+ T cells and B lymphocytes.
      • SARS-CoV-2 is able to infect the liver and cause conspicuous hepatic cytopathy.
      • Massive apoptosis and binuclear hepatocytes were the predominant histological features of SARS-CoV-2-infected liver.

      Background & Aims

      Liver enzyme abnormalities are common in patients with coronavirus disease 2019 (COVID-19). Whether or not severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to liver damage per se remains unknown. Herein, we reported the clinical characteristics and liver pathological manifestations of COVID-19 patients with liver enzyme abnormalities.


      We analyzed 156 patients diagnosed with COVID-19 from 2 designated centers in China and compared clinical features between patients with or without elevated aminotransferases. Postmortem liver biopsies were obtained from 2 cases who had elevated aminotransferases. We investigated the patterns of liver impairment by electron microscopy, immunohistochemistry, TUNEL assay and pathological studies.


      Sixty-four out of 156 (41.0%) patients with COVID-19 had elevated aminotransferases. The median levels of alanine aminotransferase were 50 U/L vs. 19 U/L, respectively, aspartate aminotransferase were 45.5 U/L vs. 24 U/L, respectively in abnormal and normal aminotransferase groups. Liver enzyme abnormalities were associated with disease severity, as well as a series of laboratory tests including higher alveolar-arterial oxygen partial pressure difference, higher gamma-glutamyltransferase, lower albumin, decreased CD4+ T cells and B lymphocytes. Ultrastructural examination identified typical coronavirus particles, characterized by spike structures, in the cytoplasm of hepatocytes in 2 COVID-19 cases. SARS-CoV-2-infected hepatocytes displayed conspicuous mitochondrial swelling, endoplasmic reticulum dilatation and glycogen granule decrease. Histologically, massive hepatic apoptosis and some binuclear hepatocytes were observed. Taken together, both ultrastructural and histological evidence indicated a typical lesion of viral infection. Immunohistochemical results showed scarce 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 the liver directly contributes to hepatic impairment in patients with COVID-19. Hence, a surveillance of viral clearance in liver and long-term outcome of COVID-19 is required.

      Lay summary

      Liver enzyme abnormalities are common in patients with coronavirus disease 2019 (COVID-19). We reported the clinical characteristics and liver pathological manifestations of COVID-19 patients with elevated liver enzymes. Our findings suggested that SARS-CoV-2 infection of the liver is a crucial factor contributing to hepatic impairment in patients with COVID-19.

      Graphical abstract


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        • Zhu N.
        • Zhang D.
        • Wang W.
        • Li X.
        • Yang B.
        • Song J.
        • et al.
        A novel coronavirus from patients with pneumonia in China, 2019.
        N Engl J Med. 2020; 382: 727-733
        • Zhou P.
        • Yang X.L.
        • Wang X.G.
        • Hu B.
        • Zhang L.
        • Zhang W.
        • et al.
        A pneumonia outbreak associated with a new coronavirus of probable bat origin.
        Nature. 2020; 579: 270-273
        • Xu X.W.
        • Wu X.X.
        • Jiang X.G.
        • Xu K.J.
        • Ying L.J.
        • Ma C.L.
        • et al.
        Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series.
        BMJ. 2020; 368: m606
        • Huang C.
        • Wang Y.
        • Li X.
        • Ren L.
        • Zhao J.
        • Hu Y.
        • et al.
        Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.
        Lancet. 2020; 395: 497-506
        • Chen N.
        • Zhou M.
        • Dong X.
        • Qu J.
        • Gong F.
        • Han Y.
        • et al.
        Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.
        Lancet. 2020; 395: 507-513
      1. The New Coronavirus Pneumonia Prevention and Control Program. National Health Commission of China. 5th ed. National Health Commission of China, China2020
        • Lee N.
        • Hui D.
        • Wu A.
        • Chan P.
        • Cameron P.
        • Joynt G.M.
        • et al.
        A major outbreak of severe acute respiratory syndrome in Hong Kong.
        N Engl J Med. 2003; 348: 1986-1994
        • Tsang K.W.
        • Ho P.L.
        • Ooi G.C.
        • Yee W.K.
        • Wang T.
        • Chan-Yeung M.
        • et al.
        A cluster of cases of severe acute respiratory syndrome in Hong Kong.
        N Engl J Med. 2003; 348: 1977-1985
        • Chau T.N.
        • Lee K.C.
        • Yao H.
        • Tsang T.Y.
        • Chow T.C.
        • Yeung Y.C.
        • et al.
        SARS-associated viral hepatitis caused by a novel coronavirus: report of three cases.
        Hepatology. 2004; 39: 302-310
        • Poutanen S.M.
        • Low D.E.
        • Henry B.
        • Finkelstein S.
        • Rose D.
        • Green K.
        • et al.
        Identification of severe acute respiratory syndrome in Canada.
        N Engl J Med. 2003; 348: 1995-2005
        • Li W.
        • Moore M.J.
        • Vasilieva N.
        • Sui J.
        • Wong S.K.
        • Berne M.A.
        • et al.
        Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus.
        Nature. 2003; 426: 450-454
        • Hamming I.
        • Timens W.
        • Bulthuis M.L.
        • Lely A.T.
        • Navis G.
        • van Goor H.
        Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis.
        J Pathol. 2004; 203: 631-637
        • Cheung O.Y.
        • Chan J.W.
        • Ng C.K.
        • Koo C.K.
        The spectrum of pathological changes in severe acute respiratory syndrome (SARS).
        Histopathology. 2004; 45: 119-124
        • Chen J.
        • Subbarao K.
        The immunobiology of SARS∗.
        Annu Rev Immunol. 2007; 25: 443-472
        • Chen G.
        • Wu D.
        • Guo W.
        • Cao Y.
        • Huang D.
        • Wang H.
        • et al.
        Clinical and immunologic features in severe and moderate coronavirus disease 2019.
        J Clin Invest. 2020; 130: 2620-2629
        • Henrion J.
        • Schapira M.
        • Luwaert R.
        • Colin L.
        • Delannoy A.
        • Heller F.R.
        Hypoxic hepatitis: clinical and hemodynamic study in 142 consecutive cases.
        Medicine (Baltimore). 2003; 82: 392-406
        • Seeto R.K.
        • Fenn B.
        • Rockey D.C.
        Ischemic hepatitis: clinical presentation and pathogenesis.
        Am J Med. 2000; 109: 109-113
        • Bessone F.
        • Dirchwolf M.
        • Rodil M.A.
        • Razori M.V.
        • Roma M.G.
        Review article: drug-induced liver injury in the context of nonalcoholic fatty liver disease - a physiopathological and clinical integrated view.
        Aliment Pharmacol Ther. 2018; 48: 892-913
        • Gordon A.
        • McLean C.A.
        • Pedersen J.S.
        • Bailey M.J.
        • Roberts S.K.
        Hepatic steatosis in chronic hepatitis B and C: predictors, distribution and effect on fibrosis.
        J Hepatol. 2005; 43: 38-44
        • Nishida N.
        • Chiba T.
        • Ohtani M.
        • Yoshioka N.
        Sudden unexpected death of a 17-year-old male infected with the influenza virus.
        Leg Med (Tokyo). 2005; 7: 51-57

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