Direct or Collateral Liver Damage in SARS-CoV-2–Infected Patients

Maria J. Lizardo-Thiebaud; Eduardo Cervantes-Alvarez; Nathaly Limon-de la Rosa; Farid Tejeda-Dominguez; Mildred Palacios-Jimenez; Osvely Méndez-Guerrero; Marco Delaye-Martinez; Fatima Rodriguez-Alvarez; Beatriz Romero-Morales; Wei-Hui Liu; Christene A. Huang; David Kershenobich; Nalu Navarro-Alvarez

doi:10.1055/s-0040-1715108

Seminars in Liver Disease, Inhaltsverzeichnis

Semin Liver Dis 2020; 40(03): 321-330
DOI: 10.1055/s-0040-1715108

Review Article

Direct or Collateral Liver Damage in SARS-CoV-2–Infected Patients

Maria J. Lizardo-Thiebaud‡^*

¹Department of Molecular Biology, Universidad Panamericana, School of Medicine, Campus México, Mexico City

,

Eduardo Cervantes-Alvarez‡^*

²Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

³PECEM, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico

,

Nathaly Limon-de la Rosa

²Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

,

Farid Tejeda-Dominguez

¹Department of Molecular Biology, Universidad Panamericana, School of Medicine, Campus México, Mexico City

,

Mildred Palacios-Jimenez

²Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

⁴Department of Medicine, Universidad Veracruzana, Veracruz, Mexico

,

Osvely Méndez-Guerrero

²Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

,

Marco Delaye-Martinez

²Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

³PECEM, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico

,

Fatima Rodriguez-Alvarez

²Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

⁴Department of Medicine, Universidad Veracruzana, Veracruz, Mexico

,

Beatriz Romero-Morales

²Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

,

Wei-Hui Liu

⁵Department of Gastroenterology and Hepatology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan Province, China

,

Christene A. Huang

⁶Department of Surgery, University of Colorado Anschutz Medical Campus, Denver, Colorado

,

David Kershenobich

²Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

,

Nalu Navarro-Alvarez^*

¹Department of Molecular Biology, Universidad Panamericana, School of Medicine, Campus México, Mexico City

²Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

⁶Department of Surgery, University of Colorado Anschutz Medical Campus, Denver, Colorado

› Institutsangaben

Abstract

Liver injury can result from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with more than one-third of COVID-19 patients exhibiting elevated liver enzymes. Microvesicular steatosis, inflammation, vascular congestion, and thrombosis in the liver have been described in autopsy samples from COVID-19 patients. Several factors, including direct cytopathic effect of the virus, immune-mediated collateral damage, or an exacerbation of preexisting liver disease may contribute to liver pathology in COVID-19. Due to its immunological functions, the liver is an organ likely to participate in the viral response against SARS-CoV-2 and this may predispose it to injury. A better understanding of the mechanism contributing to liver injury is needed to develop and implement early measures to prevent serious liver damage in patients suffering from COVID-19. This review summarizes current reports of SARS-CoV-2 with an emphasis on how direct infection and subsequent severe inflammatory response may contribute to liver injury in patients with and without preexisting liver disease.

Keywords

liver - SARS-CoV-2 - COVID-19 - ACE2 - inflammasome

Volltext

Referenzen

References
1 ProMED. Undiagnosed pneumonia - China. Available at: https://promedmail.org/promed-post/?id=6864153 . Accessed May 1, 2020
2 World Health Organization. WHO Coronavirus Disease (COVID-19) Dashboard. Available at: https://covid19.who.int . Accessed July 12, 2020
3 Centers for Disease Control and Prevention. Coronavirus (COVID-19). Available at: https://www.cdc.gov/coronavirus/2019-ncov/index.html . Accessed May 1, 2020
4 Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA 2020; 323 (13) 1239-1242
5 McMichael TM, Currie DW, Clark S. , et al; Public Health–Seattle and King County, EvergreenHealth, and CDC COVID-19 Investigation Team. Epidemiology of COVID-19 in a long-term care facility in King County, Washington. N Engl J Med 2020; 382 (21) 2005-2011
6 Huang C, Wang Y, Li X. , et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395 (10223): 497-506
7 Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020; 395 (10229): 1033-1034
8 Siu KL, Yuen KS, Castaño-Rodriguez C. , et al. Severe acute respiratory syndrome coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of ASC. FASEB J 2019; 33 (08) 8865-8877
9 Chau TN, Lee KC, Yao H. , et al. SARS-associated viral hepatitis caused by a novel coronavirus: report of three cases. Hepatology 2004; 39 (02) 302-310
10 Ng DL, Al Hosani F, Keating MK. , et al. Clinicopathologic, immunohistochemical, and ultrastructural findings of a fatal case of Middle East respiratory syndrome coronavirus infection in the United Arab Emirates, April 2014. Am J Pathol 2016; 186 (03) 652-658
11 Amanat F, Krammer F. SARS-CoV-2 vaccines: status report. Immunity 2020; 52 (04) 583-589
12 Wang D, Hu B, Hu C. , et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020; 323 (11) 1061-1069
13 Zhang C, Shi L, Wang F-S. Liver injury in COVID-19: management and challenges. Lancet Gastroenterol Hepatol 2020; 5 (05) 428-430
14 Zhou P, Yang XL, Wang XG. , et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579 (7798): 270-273
15 Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science 2020; 367 (6485): 1444-1448
16 Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y, Zuo W. Single-cell RNA expression profiling of ACE2, the receptor of SARS-CoV-2. Am J Respir Crit Care Med 2020;
17 Kim D, Lee J-Y, Yang J-S, Kim JW, Kim VN, Chang H. The architecture of SARS-CoV-2 transcriptome. Cell 2020; 181 (04) 914-921.e10
18 Tai W, He L, Zhang X. , et al. Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine. Cell Mol Immunol 2020; 17 (06) 613-620
19 Ou X, Liu Y, Lei X. , et al. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun 2020; 11 (01) 1620
20 Hoffmann M, Kleine-Weber H, Schroeder S. , et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181 (02) 271-280.e8
21 Shang J, Wan Y, Luo C. , et al. Cell entry mechanisms of SARS-CoV-2. Proc Natl Acad Sci U S A 2020; 117 (21) 11727-11734
22 Wang Q, Zhang Y, Wu L. , et al. Structural and functional basis of SARS-CoV-2 entry by using human ACE2. Cell 2020; 181 (04) 894-904.e9
23 Shang J, Ye G, Shi K. , et al. Structural basis of receptor recognition by SARS-CoV-2. Nature 2020; 581 (7807): 221-224
24 Recalcati S. Cutaneous manifestations in COVID-19: a first perspective. J Eur Acad Dermatol Venereol 2020; 34 (05) e212-e213
25 Castaño-Rodriguez C, Honrubia JM, Gutiérrez-Álvarez J. , et al. Role of severe acute respiratory syndrome coronavirus viroporins E, 3a, and 8a in replication and pathogenesis. MBio 2018; 9 (03) e02325-e17
26 Yang X, Yu Y, Xu J. , et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med 2020; 8 (05) 475-481
27 Meduri GU, Kohler G, Headley S, Tolley E, Stentz F, Postlethwaite A. Inflammatory cytokines in the BAL of patients with ARDS. Persistent elevation over time predicts poor outcome. Chest 1995; 108 (05) 1303-1314
28 Dolinay T, Kim YS, Howrylak J. , et al. Inflammasome-regulated cytokines are critical mediators of acute lung injury. Am J Respir Crit Care Med 2012; 185 (11) 1225-1234
29 Chen IY, Moriyama M, Chang M-F, Ichinohe T. Severe acute respiratory syndrome coronavirus viroporin 3a activates the NLRP3 inflammasome. Front Microbiol 2019; 10: 50
30 Fung S-Y, Yuen K-S, Ye Z-W, Chan C-P, Jin D-Y. A tug-of-war between severe acute respiratory syndrome coronavirus 2 and host antiviral defence: lessons from other pathogenic viruses. Emerg Microbes Infect 2020; 9 (01) 558-570
31 Jose RJ, Manuel A. COVID-19 cytokine storm: the interplay between inflammation and coagulation. Lancet Respir Med 2020; 8 (06) e46-e47
32 Yang Z, Du J, Chen G. , et al. Coronavirus MHV-A59 infects the lung and causes severe pneumonia in C57BL/6 mice. Virol Sin 2014; 29 (06) 393-402
33 Zalinger ZB, Elliott R, Weiss SR. Role of the inflammasome-related cytokines IL-1 and IL-18 during infection with murine coronavirus. J Neurovirol 2017; 23 (06) 845-854
34 Lin SH, Fu J, Wang CJ. , et al. Inflammation elevated IL-33 originating from the lung mediates inflammation in acute lung injury. Clin Immunol 2016; 173: 32-43
35 Chakraborty D, Zenker S, Rossaint J. , et al. Alarmin S100A8 activates alveolar epithelial cells in the context of acute lung injury in a TLR4-dependent manner. Front Immunol 2017; 8: 1493
36 Sun S, Sursal T, Adibnia Y. , et al. Mitochondrial DAMPs increase endothelial permeability through neutrophil dependent and independent pathways. PLoS One 2013; 8 (03) e59989
37 Heymann F, Tacke F. Immunology in the liver--from homeostasis to disease. Nat Rev Gastroenterol Hepatol 2016; 13 (02) 88-110
38 Qi F, Qian S, Zhang S, Zhang Z. Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem Biophys Res Commun 2020; 526 (01) 135-140
39 Paizis G, Tikellis C, Cooper ME. , et al. Chronic liver injury in rats and humans upregulates the novel enzyme angiotensin converting enzyme 2. Gut 2005; 54 (12) 1790-1796
40 Chen N, Zhou M, Dong X. , et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020; 395 (10223): 507-513
41 Zippi M, Fiorino S, Occhigrossi G, Hong W. Hypertransaminasemia in the course of infection with SARS-CoV-2: incidence and pathogenetic hypothesis. World J Clin Cases 2020; 8 (08) 1385-1390
42 Barton LM, Duval EJ, Stroberg E, Ghosh S, Mukhopadhyay S. COVID-19 autopsies, Oklahoma, USA. Am J Clin Pathol 2020; 153 (06) 725-733
43 Tian S, Xiong Y, Liu H. , et al. Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies. Mod Pathol 2020; 33 (06) 1007-1014
44 Hanley B, Lucas SB, Youd E, Swift B, Osborn M. Autopsy in suspected COVID-19 cases. J Clin Pathol 2020; 73 (05) 239-242
45 Chai X, Hu L, Zhang Y. , et al. Specific ACE2 expression in cholangiocytes may cause liver damage after 2019-nCoV infection. bioRxiv 2020;
46 Zhao B, Ni C, Gao R. , et al. Recapitulation of SARS-CoV-2 infection and cholangiocyte damage with human liver ductal organoids. Protein Cell 2020; (Epub ahead of print)
47 Lax SF, Skok K, Zechner P. , et al. Pulmonary arterial thrombosis in COVID-19 with fatal outcome: results from a prospective, single-center, clinicopathologic case series. Ann Intern Med 2020; (Epub ahead of print)
48 Zhang Y, Zheng L, Liu L, Zhao M, Xiao J, Zhao Q. Liver impairment in COVID-19 patients: a retrospective analysis of 115 cases from a single centre in Wuhan city, China. Liver Int 2020; (Epub ahead of print)
49 Zhang W, Li C, Liu B. , et al. Pioglitazone upregulates hepatic angiotensin converting enzyme 2 expression in rats with steatohepatitis. Ann Hepatol 2013; 12 (06) 892-900
50 Ding Y, He L, Zhang Q. , et al. Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways. J Pathol 2004; 203 (02) 622-630
51 Wang Y, Liu S, Liu H. , et al. SARS-CoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19. J Hepatol 2020; S0168-8278 (20) 30294-4
52 Maini MK, Boni C, Lee CK. , et al. The role of virus-specific CD8(+) cells in liver damage and viral control during persistent hepatitis B virus infection. J Exp Med 2000; 191 (08) 1269-1280
53 Xu J, Zhao S, Teng T. , et al. Systematic comparison of two animal-to-human transmitted human coronaviruses: SARS-CoV-2 and SARS-CoV. Viruses 2020; 12 (02) 244
54 Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol 2017; 39 (05) 529-539
55 Chan HL, Kwan AC, To KF. , et al. Clinical significance of hepatic derangement in severe acute respiratory syndrome. World J Gastroenterol 2005; 11 (14) 2148-2153
56 Dizier S, Forel J-M, Ayzac L. , et al; ACURASYS Study Investigators, PROSEVA Study Group. Early hepatic dysfunction is associated with a worse outcome in patients presenting with acute respiratory distress syndrome: a post-hoc analysis of the ACURASYS and PROSEVA studies. PLoS One 2015; 10 (12) e0144278
57 Duan ZP, Chen Y, Zhang J. , et al. [Clinical characteristics and mechanism of liver injury in patients with severe acute respiratory syndrome]. Zhonghua Gan Zang Bing Za Zhi 2003; 11 (08) 493-496
58 Wu C, Chen X, Cai Y. , et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med 2020; (Epub ahead of print)
59 Tu W, Satoi S, Zhang Z. , et al. Hepatocellular dysfunction induced by nitric oxide production in hepatocytes isolated from rats with sepsis. Shock 2003; 19 (04) 373-377
60 Sproston NR, Ashworth JJ. Role of C-reactive protein at sites of inflammation and infection. Front Immunol 2018; 9: 754
61 Yang F, Shi S, Zhu J, Shi J, Dai K, Chen X. Analysis of 92 deceased patients with COVID-19. J Med Virol 2020; 15 (Apr):
62 Jin X, Lian JS, Hu JH. , et al. Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms. Gut 2020; 69 (06) 1002-1009
63 Wu J, Liu J, Zhao X. , et al. Clinical characteristics of imported cases of COVID-19 in Jiangsu Province: a multicenter descriptive study. Clin Infect Dis 2020; (Epub ahead of print)
64 Li X, Wang L, Yan S. , et al. Clinical characteristics of 25 death cases with COVID-19: A retrospective review of medical records in a single medical center, Wuhan, China. Int J Infect Dis 2020; 94: 128-132
65 Wang Y, Zhu F, Wang C. , et al. The risk of children hospitalized with severe COVID-19 in Wuhan. Pediatr Infect Dis J 2020; 39 (07) e91-e94
66 Xie H, Zhao J, Lian N, Lin S, Xie Q, Zhuo H. Clinical characteristics of non-ICU hospitalized patients with coronavirus disease 2019 and liver injury: a retrospective study. Liver Int 2020; 40 (06) 1321-1326
67 Lei F, Liu YM, Zhou F. , et al. Longitudinal association between markers of liver injury and mortality in COVID-19 in China. Hepatology 2020; (Epub ahead of print)
68 Fan Z, Chen L, Li J. , et al. Clinical features of COVID-19-related liver damage. Clin Gastroenterol Hepatol 2020; 18 (07) 1561-1566
69 Cai Q, Huang D, Yu H. , et al. COVID-19: abnormal liver function tests. J Hepatol 2020; S0168-8278(20)30218-X
70 Wang X, Fang X, Cai Z. , et al. Comorbid chronic diseases and acute organ injuries are strongly correlated with disease severity and mortality among COVID-19 patients: a systemic review and meta-analysis. Research (Wash D C) 2020; 2020: 2402961
71 Ji D, Qin E, Xu J. , et al. Non-alcoholic fatty liver diseases in patients with COVID-19: a retrospective study. J Hepatol 2020; S0168-8278(20)30206-3
72 Singh S, Khan A. Clinical characteristics and outcomes of COVID-19 among patients with pre-existing liver disease in United States: a multi-center research network study. Gastroenterology 2020; (Epub ahead of print)
73 Zhu L, She Z-G, Cheng X. , et al. Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing type 2 diabetes. Cell Metab 2020; 31 (06) 1068-1077.e3