Case of severe liver damage in COVID-19
https://doi.org/10.21518/2079-701X-2021-5-84-91
Abstract
The 2019 outbreak of coronavirus disease (COVID-19) caused by severe acute coronavirus 2 respiratory syndrome (SARS-CoV-2) has been a global concern since December 2019. Although most patients with COVID-19 have mild clinical manifestations, in about 5% of these patients the disease eventually progresses to severe lung injury or even multiple organ dysfunction. This situation presents various problems for hepatology. In the context of liver damage in patients with COVID-19, several key problems need to be addressed. For example, it is important to determine whether a SARS-CoV-2 can directly enter the liver, especially when it appears that ACE2 is marginally expressed in hepatocytes. In addition, the mechanisms underlying liver dysfunction in patients with COVID-19 are multifactorial and are associated with hyperinflammation, dysregulated immune responses, abnormal coagulation, and drugs. The article describes the potential pathogenesis of liver damage associated with COVID-19. Histopathological evidence suggests a marked disruption of the intrahepatic network of blood vessels secondary to systemic changes caused by a virus that can trigger a coagulation cascade and damage the endothelial layer of blood vessels. There is also a clinical case of polyethylene damage to the liver in a young man who led to death. Against the background of infection COVID-19 he developed massive thrombosis of the liver vessels, followed by the development of necrosis — fibrosis — cirrhosis — acute liver failure, which caused death.
About the Authors
E. Yu. Plotnikova
Kemerovo State Medical University
Russian Federation
Russian Federation
Dr. Sci. (Med.), Professor of the Department of Polyclinic Therapy, Postgraduate training of doctors and nursing, Head of the Clinical Gastroenterology Course,
22a, Voroshilov St., Kemerovo, 650029
E. N. Baranova
Kemerovo State Medical University;
Podgorbunsky Kuzbass Clinical Hospital of Emergency Medical Care
Russian Federation
Russian Federation
Cand. Sci. (Med.), Associate Professor of Department of Hospital Therapy and Clinical Pharmacology, 22a, Voroshilov St., Kemerovo, 650029;
22, Bldg. 2, Nikolay Ostrovsky St., Kemerovo, 65000
M. S. Karyagina
Podgorbunsky Kuzbass Clinical Hospital of Emergency Medical Care
Russian Federation
Russian Federation
Gastroenterologist, Gastroenterological Department, Kuzbass Hepatology Center,
22, Bldg. 2, Nikolay Ostrovsky St., Kemerovo, 65000
O. A. Vorosova
Podgorbunsky Kuzbass Clinical Hospital of Emergency Medical Care
Russian Federation
Russian Federation
Gfstroenterologist, Gastroenterological Department, Kuzbass Hepatology Center,
22, Bldg. 2, Nikolay Ostrovsky St., Kemerovo, 65000
K. A. Krasnov
Kemerovo State Medical University;
Kuzbass Hepatology Center, Podgorbunsky Kuzbass Clinical Hospital of Emergency Medical Care
Russian Federation
Russian Federation
Cand. Sci. (Med.), Associate Professor of Department of Hospital Surgery, 22a, Voroshilov St., Kemerovo, 650029;
Director, 22, Bldg. 2, Nikolay Ostrovsky St., Kemerovo, 65000
References
1. Xie M., Chen Q. Insight into 2019 novel coronavirus – An updated interim review and lessons from SARS-CoV and MERS-CoV. Int J Infect Dis. 2020;94: 119–124. doi: 10.1016/j.ijid.2020.03.071.
2. Zhang C., Shi L., Wang F.S. Liver injury in COVID-19: management and challenges. Lancet Gastroenterol Hepatol. 2020;5(5):428–430. doi: 10.1016/S2468-1253(20)30057-1.
3. Xu L., Liu J., Lu M., Yang D., Zheng X. Liver injury during highly pathogenic human coronavirus infections. Liver Int. 2020;40(5):998–1004. doi: 10.1111/liv.14435.
4. Wiersinga W.J., Rhodes A., Cheng A.C., Peacock S.J., Prescott H.C. Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID- 19): A Review. JAMA. 2020;324(8):782–793. doi: 10.1001/jama.2020.12839.
5. Li H., Liu L., Zhang D., Xu J., Dai H., Tang N. et al. SARS-CoV-2 and viral sepsis: observations and hypotheses. Lancet. 2020;395(10235):1517–1520. doi: 10.1016/S0140-6736(20)30920-X.
6. Marra M.A., Jones S.J., Astell C.R., Holt R.A., Brooks-Wilson A., Butterfield Y.S. et al. The genome sequence of the SARS-associated coronavirus. Science. 2003;300(5624):1399–1404. doi: 10.1126/science.1085953.
7. Andersen K.G., Rambaut A., Lipkin W.I., Holmes E.C., Garry R.F. The proximal origin of SARS-CoV-2. Nat Med. 2020;26(4):450–452. doi: 10.1038/s41591-020-0820-9.
8. De Wit E., Van Doremalen N., Falzarano D., Munster V.J. SARS and MERS: Recent insights into emerging coronaviruses. Nat Rev Microbiol. 2016;14(8):523–534. doi: 10.1038/nrmicro.2016.81.
9. Hoffmann M., Kleine-Weber H., Schroeder S., Krüger N., Herrler T., Erichsen S. et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor Article SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181(2):271–280.e8. doi: 10.1016/j.cell.2020.02.052.
10. 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(7798):270–273. doi: 10.1038/s41586-020-2012-7.
11. 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(10223):497–506. doi: 10.1016/S0140-6736(20)30183-5.
12. Guan W., Ni Z.Y., Hu Y., Liang W.H., Ou C.Q., He J.X. et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382(18):1708–1720. doi: 10.1056/NEJMoa2002032.
13. Skok K., Stelzl E., Trauner M., Kessler H.H., Lax S.F. Post-mortem viral dynamics and tropism in COVID-19 patients in correlation with organ damage. Virchows Arch. 2020;478(2):343–353. doi: 10.1007/s00428-020-02903-8.
14. Li R., Qiao S., Zhang G. Analysis of angiotensin-converting enzyme 2 (ACE2) from different species sheds some light on cross-species receptor usage of a novel coronavirus 2019-nCoV. J Infect. 2020;80(4):469–496. doi: 10.1016/j.jinf.2020.02.013.
15. Xu H., Zhong L., Deng J., Peng J., Dan H., Zeng X. et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020;12(1):8. doi: 10.1038/s41368-020-0074-x.
16. Turner A.J., Hiscox J.A., Hooper N.M. ACE2: From vasopeptidase to SARS virus receptor. Trends Pharmacol Sci. 2004;25(6):291–294. doi: 10.1016/j.tips.2004.04.001.
17. Oyelade T., Alqahtani J., Canciani G. Prognosis of COVID-19 in Patients with Liver and Kidney Diseases: An Early Systematic Review and Meta-Analysis. Trop Med Infect Dis. 2020;5(2):80. doi: 10.3390/tropicalmed5020080.
18. Zhou F., Yu T., Du R., Fan G., Liu Y., Liu Z. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–1062. doi: 10.1016/S0140-6736(20)30566-3.
19. Wu C., Chen X., Cai Y., Xia J., Zhou X., Xu S. 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;180(7):934–943. doi: 10.1001/jamainternmed.2020.0994.
20. Bangash M.N., Patel J., Parekh D. COVID-19 and the liver: little cause for concern. Lancet Gastroenterol Hepatol. 2020;5(6):529–530. doi: 10.1016/S2468-1253(20)30084-4.
21. Boeckmans J., Rodrigues R.M., Demuyser T., Piérard D., Vanhaecke T., Rogiers V. COVID-19 and drug-induced liver injury: a problem of plenty or a petty point? Arch Toxicol. 2020;94(4):1367–1369. doi: 10.1007/s00204-020-02734-1.
22. Garrido I., Liberal R., Macedo G. Review article: COVID-19 and liver disease – what we know on 1st May 2020. Aliment Pharmacol Ther. 2020;52(2):267–275. doi: 10.1111/apt.15813.
23. Kulkarni A.V., Kumar P., Tevethia H.V., Premkumar M., Arab J.P., Candia R. et al. Systematic review with meta-analysis: liver manifestations and outcomes in COVID-19. Aliment Pharmacol Ther. 2020;52(4):548–599. doi: 10.1111/apt.15916.
24. Bertolini A., van de Peppel I.P., Bodewes F.A., Moshage H., Fantin A., Farinati F. et al. Abnormal liver function tests in COVID-19 patients: relevance and potential pathogenesis. Hepatology. 2020;72(5):1864–1872. doi: 10.1002/hep.31480.
25. Wu J., Song S., Cao H.C., Li L.J. Liver diseases in COVID-19: Etiology, treatment and prognosis. World J Gastroenterol. 2020;26(19):2286–2293. doi: 10.3748/wjg.v26.i19.2286.
26. Yadav D.K., Singh A., Zhang Q., Bai X., Zhang W., Yadav R.K. et al. Involvement of liver in COVID-19: systematic review and meta-analysis. Gut. 2021;70(4):807–809. doi: 10.1136/gutjnl-2020-322072.
27. Jothimani D., Venugopal R., Abedin M.F., Kaliamoorthy I., Rela M. COVID-19 and Liver. J Hepatol. 2020;73(5):1231–1240. doi: 10.1016/j.jhep.2020.06.006.
28. Wang Y., Liu S., Liu H., Li W., Lin F., Jiang L. et al. SARS-CoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19. J Hepatol. 2020;73(4):807–816. J Hepatol. 2020;73(4):807–816. doi: 10.1016/j.jhep.2020.05.002.
29. Wang Y., Lu F., Zhao J. Reply to: Correspondence relating to “SARS-CoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19”. J Hepatol. 2020;73(4):996–998. doi: 10.1016/j.jhep.2020.06.028.
30. Kucharski A.J., Russell T.W., Diamond C., Liu Y., Edmunds J., Funk S., Eggo R.M. Early dynamics of transmission and control of COVID-19: a mathematical modelling study. Lancet Infect Dis. 2020;20(5):553–558. doi: 10.1016/S1473-3099(20)30144-4.
31. Kumar M.P., Mishra S., Jha D.K., Shukla J., Choudhury A., Mohindra R. et al. Coronavirus disease (COVID-19) and the liver: a comprehensive systematic review and meta-analysis. Hepatol Int. 2020;14(5):711–722. doi: 10.1007/s12072-020-10071-9.
32. Paliogiannis P., Zinellu A. Bilirubin levels in patients with mild and severe Covid-19: A pooled analysis. Liver Int. 2020;40(7):1787–1788. doi: 10.1111/liv.14477.
33. Parasa S., Desai M., Thoguluva Chandrasekar V., Patel H.K., Kennedy K.F., Roesch T. et al. Prevalence of Gastrointestinal Symptoms and Fecal Viral Shedding in Patients With Coronavirus Disease 2019. JAMA Netw Open. 2020;3(6):e2011335. doi: 10.1001/jamanetworkopen.2020.11335.
34. Cai Q., Huang D., Yu H., Zhu Z., Xia Z., Su Y. et al. COVID-19: Abnormal liver function tests. J Hepatol. 2020;73(3):566–574. doi: 10.1016/j. jhep.2020.04.006.
35. Bernal-Monterde V., Casas-Deza D., Letona-Giménez L., de la Llama-Celis N., Calmarza P., Sierra-Gabarda O. et al. SARS-CoV-2 Infection Induces a Dual Response in Liver Function Tests: Association with Mortality during Hospitalization. Biomedicines. 2020;8(9):328. doi: 10.3390/biomedicines8090328.
36. Pascarella G., Strumia A., Piliego C., Bruno F., oDel Buono R., Costa F. et al. COVID-19 diagnosis and management: a comprehensive review. J Intern Med. 2020;288(2):192–206. doi: 10.1111/joim.13091.
37. Varga Z., Flammer A.J., Steiger P., Haberecker M., Andermatt R., Zinkernagel A.S. et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395(10234):1417–1418. doi: 10.1016/S0140-6736(20)30937-5.
38. Liu W., Tao Z.W., Wang L., Yuan M.L., Liu K., Zhou L. et al. Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease. Chin Med J (Engl). 2020;133(9):1032–1038. doi: 10.1097/CM9.0000000000000775.
39. Trevenzoli M., Guarnaccia A., Alberici I., Fassan M., Di Meco E., Farinati F., Cattelan A.M. SARS-CoV-2 and hepatitis. J Gastrointestin Liver Dis. 2020;29(3):473–475. doi: 10.15403/jgld-2747.
40. Gholizadeh P., Safari R., Marofi P., Zeinalzadeh E., Pagliano P., Ganbarov K. et al. Alteration of Liver Biomarkers in Patients with SARS-CoV-2 (COVID- 19). J Inflamm Res. 2020;13:285–292. doi: 10.2147/JIR.S257078.
41. Lax S.F., Skok K., Zechner P., Kessler H.H., Kaufmann N., Koelblinger C. et al. Pulmonary arterial thrombosis in covid-19 with fatal outcome: results from a prospective, single-center, clinicopathologic case series. Ann Intern Med. 2020;173(5):350–361. doi: 10.7326/M20-2566.
42. Ji D., Qin E., Xu J., Zhang D., Cheng G., Wang Y., Lau G. et al. Non-alcoholic fatty liver diseases in patients with COVID-19: A retrospective study. J Hepatol. 2020;73(2):451–453. doi: 10.1016/j.jhep.2020.03.044.
43. Sonzogni A., Previtali G., Seghezzi M., Grazia Alessio M., Gianatti A., Licini L. et al. Liver histopathology in severe COVID 19 respiratory failure is suggestive of vascular alterations. Liver Int. 2020;40(9):2110–2116. doi: 10.1111/liv.14601.
44. Merad M., Martin J.C. Pathological inflammation in patients with COVID- 19: a key role for monocytes and macrophages. Nat Rev Immunol. 2020;20(6):355–362. doi: 10.1038/s41577-020-0331-4.
45. Manne B.K., Denorme F., Middleton E.A., Portier I., Rowley J.W., Stubben C. et al. Platelet gene expression and function in patients with COVID-19. Blood. 2020;136(11):1317–1329. doi: 10.1182/blood.2020007214.
46. Tang N., Bai H., Chen X., Gong J., Li D., Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020;18(5):1094–1099. doi: 10.1111/jth.14817.
47. Vinken M. COVID-19 and the liver: an adverse outcome pathway perspective. Toxicology. 2021;455:152765. doi: 10.1016/j.tox.2021.152765.
48. Wang D., Hu B., Hu C., Zhu F., Liu X., Zhang J. et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan. China. JAMA. 2020;323(11):1061–1069. doi: 10.1001/jama.2020.1585.
49. Duarte-Neto A.N., Monteiro R.A.A., da Silva L.F.F., Malheiros D.M.A.C., de Oliveira E.P., Theodoro-Filho J. et al. Pulmonary and systemic involvement of COVID-19 assessed by ultrasound-guided minimally invasive autopsy. Histopathology. 2020;77(2):186–197. doi: 10.1111/his.14160.
50. Mancia G., Rea F., Ludergnani M., Apolone G., Corrao G. Renin-angiotensinaldosterone system blockers and the risk of COVID-19. N Engl J Med. 2020;382(25):2431–2440. doi: 10.1056/NEJMoa2006923.
51. Chen L., Li X.J., Chen M.Q., Feng Y., Xiong C.L. The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2. Cardiovasc Res. 2020;116(6):1097– 1100. doi: 10.1093/cvr/cvaa078.
52. van der Poll T., van de Veerdonk F.L., Scicluna B.P., Netea M.G. The immunopathology of sepsis and potential therapeutic targets. Nat Rev Immunol. 2017;17:407–420. doi: 10.1038/nri.2017.36.
53. von Bruhl M.L., Stark K., Steinhart A., Chandraratne S., Konrad I., Lorenz M. et al. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J Exp Med. 2012;209(4):819–835. doi: 10.1084/jem.20112322.
54. Zuo Y., Yalavarthi S., Shi H., Gockman K., Zuo M., Madison J.A. et al. Neutrophil extracellular traps in COVID-19. JCI Insight. 2020;5(11):e138999. doi: 10.1172/jci.insight.138999.
55. Barnes B.J., Adrover J.M., Baxter-Stoltzfus A., Borczuk A., Cools-Lartigue J., Crawford J.M. et al. Targeting potential drivers of COVID-19: neutrophil extracellular traps. J Exp Med. 2020;217(6):e20200652. doi: 10.1084/jem.20200652.
56. Yao X.H., Li T.Y., He Z.C., Ping Y.F., Liu H.W., Yu S.C. et al. A pathological report of three COVID‐19 cases by minimally invasive autopsies. Zhonghua Bing Li Xue Za Zhi. 2020;49(5):411–417. doi: 10.3760/cma.j.cn112151-20200312-00193.
57. Sun J., Aghemo A., Forner A., Valenti L. COVID‐19 and liver disease. Liver Int. 2020;40(6):1278–1281. doi: 10.1111/liv.14470.
58. Tang N., Li D., Wang X., Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18(4):844–847. doi: 10.1111/jth.14768.
59. Carsana L., Sonzogni A., Nasr A., Rossi R.S., Pellegrinelli A., Zerbi P. et al. Pulmonary post‐mortem findings in a large series of COVID‐19 cases from Northern Italy. Lancet Infect Dis, accepted for publication. Lancet Infect Dis. 2020;20(10):1135–1140. doi: 10.1016/S1473-3099(20)30434-5.
60. Saviano A., Wrensch F., Ghany M.G., Baumert T.F. Liver disease and COVID-19: from Pathogenesis to Clinical Care. Hepatology. 2020. doi: 10.1002/hep.31684. 61. Sempoux C., Bioulac‐Sage P. Vascular liver lesions: contemporary views on long‐recognized entities. Virchows Arch. 2018;473(1):1–2. doi: 10.1007/s00428-018-2328-y.
61. Guido M., Pizzi M., Sacerdoti D., Giacomelli L., Rugge M., Bolognesi M. Beyond scoring: a modern histological assessment of chronic hepatitis should include tissue angiogenesis. Gut. 2014;63(8):1366–1367. doi: 10.1136/gutjnl-2013-306658.
62. Zhou F., Yu T., Du R., Fan G., Liu Y., Liu Z. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–1062. doi: 10.1016/S0140-6736(20)30566-3.
Review
For citations:
Plotnikova EY, Baranova EN, Karyagina MS, Vorosova OA, Krasnov KA. Case of severe liver damage in COVID-19. Meditsinskiy sovet = Medical Council. 2021;(5):84-91. (In Russ.) https://doi.org/10.21518/2079-701X-2021-5-84-91
Views:
707
Email this article 