Liver pathology in COVID-19

Close metadata

Recommended articles:

Pathogenesis of pulmonary fibrosis. Russian Journal of Archive of Pathology. 2024;(4):58-63

Results of detailed screening of patients who have undergone a novel coronavirus infection COVID-19. Russian Journal of Preventive Medicine. 2024;(7):16-22

A case of acute myocardial infarction of right ventricle with myomalacia and tamponade development after SARS-CoV-2 re-infection in the Loeys—Dietz syndrome patient. Russian Journal of Preventive Medicine. 2024;(7):73-76

Post-COVID syndrome in children: features of pathophysiology, diagnosis and therapy. Russian Journal of Preventive Medicine. 2024;(7):94-100

Cochleovestibular manifestations in coronavirus infection. Russian Bulletin of Otorhinolaryngology. 2024;(3):18-23

Pediatric sensorineural hearing loss related COVID-19. Clinical cases. Russian Bulletin of Otorhinolaryngology. 2024;(3):64-68

Thoracoscopic thymectomy for myasthenia gravis and non-invasive thymoma after COVID-19 pneumonia. Pirogov Russian Journal of Surgery. 2024;(8):26-33

Acute dissecting aortic aneurysm with rupture in a patient with Noonan syndrome following SARS-CoV-2 re-infection. Russian Journal of Preventive Medicine. 2024;(8):73-75

Risk Factors of Bleedings in Patients with COVID-19 Receiving Anticoagulants for Venous Thromboembolism Prevention. Journal of Venous Disorders. 2024;(3):222-231

Clinical effect of selective hemosorption of cytokines in patients with severe COVID-19: a systematic review. Russian Journal of Anesthesiology and Reanimatology. 2024;(5):103-111

The literature review presents an analysis of the pathogenesis and pathological anatomy of liver damage in COVID-19. Liver damage with the steatosis, vascular disorders, mild portal and lobular inflammatory infiltration, cholestasis and clinically — liver failure is observed in majority of the patients with COVID-19. Chronic liver diseases with infection SARS-CoV-2 tend to decompensate, which significantly worsens the prognosis of the disease. Pathogenesis of liver damage in COVID19 is unclear. There was no convincing evidence for the hypothesis of cytotoxicity for hepatocytes or cholangiocytes by SARS-CoV-2. Similar liver morphological changes described by different authors suggest their nonspecific nature and multifactorial pathogenesis related to hypoxia, cytokin storm, systemic inflammatory response syndrome, sepsis and shock, Covid-associated angio- and coagulopathy, as well as drug-induced hepatotoxicity. Further research is needed to clarify the pathogenesis and pathological anatomy of the liver pathology in COVID-19.

Keywords:

liver pathology

pathogenesis

pathological anatomy

COVID-19

Authors:

Krasnenkova S.F.

Russian University of Medicine;
Research Institute of Organization of Medicine and Medicine Management

ORCID: 0000-0002-4868-7804

Zayratyants O.V.

Russian University of Medicine;
Avtsyn Research Institute of Human Morphology of Petrovsky National Research Centre of Surgery

ORCID: 0000-0003-3606-3823

Midiber K.Yu.

Avtsyn Research Institute of Human Morphology of Petrovsky National Research Centre of Surgery;
Peoples’ Friendship University of Russia named after Patrice Lumumba

ORCID: 0000-0002-1426-968X

Mikhaleva L.M.

A.P. Avtsyn Research Institute of Human Morphology Petrovsky National Research Center of Surgery;
Russian Medical Academy of Continuous Professional Education

ORCID: 0000-0003-2052-914X

Received:

13.07.2024

Accepted:

30.10.2024

List of references:

Kukla M, Skonieczna-Zydecka K, Kotfis K, et al. COVID-19, MERS and SARS with concomitant liver injury — systematic review of the existing literature. J Clin Med. 2020;9(5):1420. https://doi.org/10.3390/jcm9051420
Zhang C, Shi L, Wang FS. Liver injury in COVID-19: management and challenges. Lancet Gastroenterol Hepatol. 2020;5(5):428-430. https://doi.org/10.1016/S2468-1253(20)30057-1
Yang C, Cai L, Xiao SY. Pathologic characteristics of digestive tract and liver in patients with coronavirus disease 2019. Gastroenterol Clin North Am. 2023;52(1):201-214. https://doi.org/10.1016/j.gtc.2022.09.003
Zanon M, Neri M, Pizzolitto S, Radaelli D, Concato M, Peruch M, D’Errico S. Liver pathology in COVID-19 related death and leading role of autopsy in the pandemic. World J Gastroenterol. 2023;29(1):200-220. https://doi.org/10.3748/wjg.v29.i1.200
Maev IV, Osadchuk MA. Liver disease during the pandemic of COVID-19 infection: prediction of the course and tactics of management. Terapevticheskii Arkhiv. 2022;94(11):1326-1332. (In Russ.). https://doi.org/10.26442/00403660.2022.11.201934
Giacomelli A, Righini E, Micheli V, et al. SARS-CoV-2 viremia and COVID-19 mortality: a prospective observational study. PLoS One. 2023;18(4):e0281052. https://doi.org/10.1371/journal.pone.0281052
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;73(4):807-816. https://doi.org/10.1016/j.jhep.2020.05.002
Chai X, Hu L, Zhang Y, et al. Specific ACE2 expression in cholangiocytes may cause liver damage after 2019-nCoV infection. bioRxiv. 2020. Published online Feb 4, 2020. (preprint). https://doi.org/10.1101/2020.02.03.931766
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;11(10):771-775. https://doi.org/10.1007/s13238-020-00718-6
Baldelli L, Marjot T, Barnes E, Barritt AS, Webb GJ, Moon AM. SARS-CoV-2 infection and liver disease: a review of pathogenesis and outcomes. Gut Liver. 2023;17(1):12-23. https://doi.org/10.5009/gnl220327
Gkogkou E, Barnasas G, Vougas K, Trougakos IP. Expression profiling meta-analysis of ACE2 and TMPRSS2, the putative anti-inflammatory receptor and priming protease of SARS-CoV-2 in human cells, and identification of putative modulators. Redox Biol. 2020;36:101615. https://doi.org/10.1016/j.redox.2020.101615
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(1):135-140. https://doi.org/10.1016/j.bbrc.2020.03.044
Cai Q, Huang D, Yu H, et al. COVID-19: abnormal liver function tests. J Hepatol. 2020;73(3):566-574. https://doi.org/10.1016/j.jhep.2020.04.006
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. https://doi.org/10.1136/gut.2004.062398
Suarez-Farinas M, Tokuyama M, Wei G, et al. Intestinal inflammation modulates the expression of ACE2 and TMPRSS2 and potentially overlaps with the pathogenesis of SARS-CoV-2-related disease. Gastroenterology. 2021;160(1):287-301.e20. https://doi.org/10.1053/j.gastro.2020.09.029
Lagana SM, Kudose S, Iuga AC, et al. Hepatic pathology in patients dying of COVID-19: a series of 40 cases including clinical, histologic, and virologic data. Mod Pathol. 2020;33(11):2147-2155. https://doi.org/10.1038/s41379-020-00649-x
Sonzogni A, Previtali G, Seghezzi M, et al. Liver histopathology in severe COVID 19 respiratory failure is suggestive of vascular alterations. Liver Int. 2020;40(9):2110-2116. https://doi.org/10.1111/liv.14601
Barnes E. Infection of liver hepatocytes with SARS-CoV-2. Nat Metab. 2022;4(3):301-302. https://doi.org/10.1038/s42255-022-00554-4
Hu WS, Jiang FY, Shu W, Zhao R, Cao JM, Wang DP. Liver injury in COVID-19: a minireview. World J Gastroenterol. 2022;28(47):6716-6731. https://doi.org/10.3748/wjg.v28.i47.6716
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. https://doi.org/10.1016/S0140-6736(20)30628-0
Sun J, Aghemo A, Forner A, Valenti L. COVID-19 and liver disease. Liver Int. 2020;40(6):1278-1281. https://doi.org/10.1111/Liv.14470
Zhu DD, Tan XM, Lu LQ, et al. Interplay between nuclear factor erythroid 2-related factor 2 and inflammatory mediators in COVID-19-related liver injury. World J Gastroenterol. 2021;27(22):2944-2962. https://doi.org/10.3748/wjg.v27.i22.2944
Coish JM, MacNeil AJ. Out of the frying pan and into the fire? Due diligence warranted for ADE in COVID-19. Microbes Infect. 2020;22(9):405-406. https://doi.org/10.1016/j.micinf.2020.06.006
Mohamed DZ, Ghoneim ME, Abu-Risha SE, Abdelsalam RA, Farag MA. Gastrointestinal and hepatic diseases during the COVID-19 pandemic: manifestations, mechanism and management. World J Gastroenterol. 2021;27(28):4504-4535. https://doi.org/10.3748/wjg.v27.i28.4504
Mishnev OD, Tumanova UN, Shchegolev AI. Liverpathology in sepsis. International Journal of Applied and Fundamental Research. 2017;8(part 2):267-271. (In Russ.). https://applied-research.ru/ru/article/view?id=11798
El-Ghiaty MA, Shoieb SM, El-Kadi AOS. Cytochrome P450-mediated drug interactions in COVID-19 patients: current findings and possible mechanisms. Med Hypotheses. 2020;144:110033. https://doi.org/10.1016/j.mehy.2020.110033
Karakike E, Giamarellos-Bourboulis EJ, Kyprianou M, Fleischmann-Struzek C, Pletz MW, Netea MG, Reinhart K, Kyriazopoulou E. Coronavirus disease 2019 as cause of viral sepsis: a systematic review and meta-analysis. Crit Care Med. 2021;49(12):2042-2057. https://doi.org/10.1097/CCM.0000000000005195
Cao X. COVID-19: immunopathology and its implications for therapy. Nat Rev Immunol. 2020;20(5):269-270. https://doi.org/10.1038/s41577-020-0308-3
Wichmann D, Sperhake JP, Litgehetmann M, et al. Autopsy findings and venous thromboembolism in patients with COVID-19: a prospective cohort study. Ann Intern Med. 2020;173(4):268-277. https://doi.org/10.7326/M20-2003
Li H, Liu L, Zhang D, Xu J, Dai H, Tang N, Su X, Cao B. SARS-CoV-2 and viral sepsis: observations and hypotheses. Lancet. 2020;395(10235):1517-1520. https://doi.org/10.1016/s0140-6736(20)30920-x
Fu Y, Cheng Y, Wu Y. Understanding SARS-CoV-2-mediated inflammatory responses: from mechanisms to potential therapeutic tools. Virol Sin. 2020;35(3):266-271. https://doi.org/10.1007/s12250-020-00207-4
Skvortsov VV, Gorbach AN. Sepsis-induced liver dysfunction: modern diagnosis and treatment strategies. Effective Pharmacotherapy. 2020;16(15):80-84. (In Russ.). https://doi.org/10.33978/2307-3586-2020-16-15-80-84
Roedl K, Jarczak D, Drolz A, et al. Severe liver dysfunction complicating course of COVID-19 in the critically ill: multifactorial cause or direct viral effect? Ann Intensive Care. 2021;11(1):44. https://doi.org/10.1186/s13613-021-00835-3
D’Ardes D, Boccatonda A, Cocco G, Fabiani S, Rossi I, Bucci M, Guagnano MT, Schiavone C, Cipollone F. Impaired coagulation, liver dysfunction and COVID-19: discovering an intriguing relationship. World J Gastroenterol. 2022;28(11):1102-1112. https://doi.org/10.3748/wjg.v28.i11.1102
Li D, Ding X, Xie M, Tian D, Xia L. COVID-19-associated liver injury: from bedside to bench. J Gastroenterol. 2021;56(3):218-230. https://doi.org/10.1007/s00535-021-01760-9
Gracia-Ramos AE, Jaquez-Quintana JO, Contreras-Omaña R, Auron M. Liver dysfunction and SARS-CoV-2 infection. World J Gastroenterol. 2021;27(26):3951-3970. https://doi.org/10.3748/wjg.v27.i26.3951
Idalsoaga F, Ayares G, Arab JP, Diaz AL. COVID-19 and indirect liver injury: a narrative synthesis of the evidence. J Clin Transl Hepatol. 2021;9(5):760-768. https://doi.org/10.14218/JCTH.2020.00140
Chen P, Zhou B. Clinical caracteristics of COVID-19 in patients with liver injury. Clin Gastroenterol Hepatol. 2020;18(12):2846-2847. https://doi.org/10.1016/j.cgh.2020.04.043
Cao J, Cai X, Chen M. Liver Injury in COVID-19: caution and management. Liver Cancer. 2020;9(5):625-626. https://doi.org/10.1159/000508696
Anirvan P, Bharali P, Gogoi M, Thuluvath PJ, Singh SP, Satapathy SK. Liver injury in COVID-19: the hepatic aspect of the respiratory syndrome — what we know so far. World J Hepatol. 2020;12(12):1182-1197. https://doi.org/10.4254/wjh.v12.i12.1182
Liu C, Jiang ZC, Shao CX, et al. Preliminary study of the relationship between novel coronavirus pneumonia and liver function damage: a multicenter study. Zhonghua Gan Zang Bing Za Zhi. 2020;28(2):107-111. (In Chinese). https://doi.org/10.3760/cma.j.issn.1007-3418.2020.02.003
Vyalov SS, Gilyuk AV. Liver and biliary tract damage induced by SARS-CoV coronavirus infection-2. Therapy. 2022;(6):140-150. (In Russ.). https://doi.org/10.18565/therapy.2022.6.140-150
Huang Q, Xie Q, Shi CC, Xiang XG, Lin LY, Gong BD, Zhao GD, Wang H, Jia NN. Expression of angiotensin-converting enzyme 2 in CCL4-induced rat liver fibrosis. Int J Mol Med. 2009;23(6): 717-723. https://doi.org/10.3892/ijmm_00000185
Hartl L, Haslinger K, Angerer M, et al. Progressive cholestasis and associated sclerosing cholangitis are frequent complications of COVID-19 in patients with chronic liver disease. Hepatology. 2022;76(6):1563-1575. https://doi.org/10.1002/hep.32582
Fassan M, Mescoli C, Sbaraglia M, et al. Liver histopathology in COVID-19 patients: a mono-institutional series of liver biopsies and autopsy specimens. Pathol Res Pract. 2021;221:153451. https://doi.org/10.1016/j.prp.2021.153451
Fiel MI, El Jamal SM, Paniz-Mondolfi A, et al. Findings of hepatic severe acute respiratory syndrome coronavirus-2 infection. Cell Mol Gastroenterol Hepatol. 2021;11(3):763-770. https://doi.org/10.1016/j.jcmgh.2020.09.015
Zairat’yants OV, ed. Pathological anatomy of COVID-19: atlas. Moscow: Research Institute for Healthcare and Medical Management of Moscow Healthcare Department; 2020;142. (In Russ.).
Zairat’yants OV, Samsonova MV, Chernyaev AL, Mishnev OD, Mikhaleva LM, Krupnov NM, Kalinin DV. COVID-19 pathology: experience of 2000 autopsies. Forensic Medicine. 2020;6(4):10-23. (In Russ.). https://doi.org/10.19048/fm340
Vishwajeet V, Purohit A, Kumar D, et al. Evaluation of liver histopathological findings of coronavirus disease 2019 by minimally invasive autopsies. J Clin Exp Hepatol. 2022;12(2): 390-397. https://doi.org/10.1016/j.jceh.2021.07.004
Pinchuk TV, Orlova NV, Suranova TG, Bonkalo TI. Mechanisms of liver damage in COVID-19. Medical Alphabet. 2020;(19):39-46. (In Russ.). https://doi.org/10.33667/2078-5631-2020-19-39-46
Chew M, Tang Z, Radcliffe C, Caruana D, Doilicho N, Ciarleglio MM, Deng Y, Garcia-Tsao G. Significant liver injury during hospitalization for COVID-19 is not associated with liver insufficiency or death. Clin Gastroenterol Hepatol. 2021;19(10):2182-2191.e7. https://doi.org/10.1016/j.cgh.2021.05.022
Campbell PT, Fix OK. Coronavirus disease-2019 and implications on the liver. Clin Liver Dis. 2023;27(1):27-45. https://doi.org/10.1016/j.cld.2022.08.003
Del Nonno F, Nardacci R, Colombo D, Visco-Comandini U, Cicalini S, Antinori A, Marchioni L, D’Offizi G, Piacentini M, Falasca L. Hepatic failure in COVID-19: is iron overload the dangerous trigger? Cells. 2021;10(5):1103. https://doi.org/10.3390/cells10051103

Close metadata