Lviv clinical bulletin 2022, 1(37)-2(38): 67-74

https://doi.org/10.25040/lkv2022.01-02.067

Liver Injuries Associated with Coronavirus Disease 2019: View on the Problem

V. Prysyazhnyuk, T. Ilashchuk, L. Voloshyna, V. Vasjuk, I. Prysiazhniuk, K. Bobkovych

Bukovinian State Medical University

Introduction. Major cardiovascular and pulmonary comorbidities, as well as diabetes mellitus and certain cancers, are associated with worse clinical outcomes of coronavirus disease-2019 (COVID-19). Meanwhile, the impact of concomitant liver diseases on the COVID-19 natural course together with the influence of the COVID-19 on the hepatic tissues have been rarely investigated.

The aim of the study was to analyse the available data regarding impact of liver pathologies on COVID-19 natural course and outcome, and, reciprocally, hepatic injuries development induced by COVID-19.

Materials and methods. Content analysis, systematic and comparative analysis, bibliosemantic method of investigation of current scientific research results on liver damage associated with COVID-19 were used.

Results. The potential mechanism of liver injury in COVID-19 is complex and includes direct cytopathic viral injury, proinflammatory cytokine outbreak, hypoxia/reperfusion damage and potential drug induced liver injury. Among the medications used for the treatment of COVID-19 patients, there are certain that could potentially cause drug-induced liver injury. Treatment of liver transplant patients can be challenging taking into consideration the possible necessity of immunosuppressive therapy correction combined with the needs to find a balance between the risk of graft rejection and effective elimination of the virus.

Conclusions. Current review of the available database revealed that liver diseases are among substantive comorbidities in COVID-19 patients alongside with liver injuries which are rather frequent complications of COVID-19 treatment. Potential drug-induced liver injuries in patients subjected tocertain antiviral agents in combination with supportive therapy drugs should be taken into consideration. Special precautions are required to prevent potential drug-to-drug interactions in case of COVID-19 treatment in liver transplant patients.

References

  1. Alqahtani SA, Schattenberg JM. Liver injury in COVID-19: The current evidence. United European Gastroenterol J. 2020;8(5):509-519.
  2. Arora N, Goldhaber SZ. Anticoagulants and transaminase elevation. Circulation. 2006;113:e698-702.
  3. Bajgain KT, Badal S, Bajgain BB, Santana MJ. Prevalence of comorbidities among individuals with COVID-19: A rapid review of current literature. Am J Infect Control. 2020;20:30637-30640.
  4. Barnes GD, Burnett A, Allen A, Blumenstein M, Clark NP, Cuker A et al. Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the anticoagulation forum. J Thromb Thrombolysis. 2020;50:72-81.
  5. Becchetti C, Zambelli MF, Pasulo L, Donato MF, Invernizzi F, Detry O et al. COVID-19 in an international European liver transplant recipient cohort. Gut. 2020;69:1832-1840.
  6. Belli LS, Fondevila C, Cortesi PA, Conti S, Karam V, Adam R et al. Protective role of tacrolimus, deleterious role of age and comorbidities in liver transplant recipients with Covid-19: results from the ELITA/ELTR multi-center European study. Gastroenterology. 2021;160(4):1151-1163.e3.
  7. Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dreyfus I, Driggin E et al. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up: JACC state-of-the-art r J Am Coll Cardiol. 2020;75:2950-2973.
  8. Blasi A, Calvo A, Prado V, Reverter E, Reverter JC, Hernández-Tejero M et al. Coagulation failure in patients with acute-on-chronic liver failure and decompensated cirrhosis: beyond the international normalized r Hepatology. 2018;68:2325-2337.
  9. Boettler T, Newsome PN, Mondelli MU, Maticic M, Cordero E, Cornberg M et al. Care of patients with liver disease during the COVID-19 pandemic: EASL-ESCMID position paper. JHEP Rep. 2020;2(3):100113.
  10. Cai Q, Huang D, Yu H, Zhu Z, Xia Z, Su Y et al. COVID-19: Abnormal liver function tests. J Hepatol. 2020;73:566-574.
  11. Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G et al. A trial of Lopinavir-Ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020;382:1787-1799.
  12. Castera L, Friedrich-Rust M, Loomba R. Noninvasive assessment of liver disease in patients with nonalcoholic fatty liver d Gastroenterology. 2019;156:1264-1281.
  13. Chai X, Hu L, Zhang Y, Han W, Lu Z, Ke A et al. Specific ACE2 expression in cholangiocytes may cause liver damage after 2019-nCoV infection Rxiv.02.03. 931766.
  14. Chandok N, Watt KDS. Pain management in the cirrhotic patient: the clinical challenge. Mayo Clinic Proc. 2010;85:451-458.
  15. 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.
  16. Christiansen HM, Lassen MR, Borris LC, Sørensen JV, Rahr HB, Jørgensen LN et al. Biologic tolerance of two different low molecular weight heparins. Semin Thromb Hemost. 1991;17:450-454.
  17. Dajti E, Cristini F, Tamanini G, Cescon M, Bazzoli F, Tamè M. COVID-19 in a young liver transplant recipient: caution for drug-drug interactions. J Gastrointestin Liver Dis. 2020;29:470.
  18. Di Giambenedetto S, Ciccullo A, Borghetti A, Gambassi G, Landi F, Visconti E et al. Off-label use of Tocilizumab in patients with SARS-CoV-2 infection. J Med Virol. 2020;92:1787-1788.
  19. El Kassas M, Alboraie M, Al Balakosy A, Abdeen N, Afify S, Abdalgaber M et al. Liver transplantation in the era of COVID-19. Arab J Gastroenterol. 2020;21:69-75.
  20. Elens L, Langman LJ, Hesselink DA, Bergan S, Moes DJAR, Molinaro M et al. Pharmacologic treatment of transplant recipients infected with SARS-CoV-2: considerations regarding therapeutic drug monitoring and drug–drug interactions. Ther Drug Monit. 2020;42:360-368.
  21. Fan Z, Chen L, Li J, Cheng X, Yang J, Tian C et al. Clinical features of COVID-19-related liver functional a Clin Gastroenterol Hepatol. 2020;18:1561-1566.
  22. Flisiak R, Zarębska-Michaluk D, Berkan-Kawińska A, Tudrujek-Zdunek M, Rogalska M, Piekarska A et al. Remdesivir-based therapy improved recovery of patients with COVID-19 in the SARSTer multicentre, real-world study. Pol Arch Intern Med. 2021;131:103-110.
  23. Fong TL, Valinluck B, Govindarajan S, Charboneau F, Adkins RH, Redeker AG. Short-term prednisone therapy affects aminotransferase activity and hepatitis C virus RNA levels in chronic hepatitis C. Gastroenterology. 1994;107:196-199.
  24. Galvez-Romero JL, Palmeros-Rojas O, Real-Ramírez FA, Sánchez-Romero S, Tome-Maxil R, Ramírez-Sandoval MP et al. Cyclosporine A plus low-dose steroid treatment in COVID-19 improves clinical outcomes in patients with moderate to severe disease. A pilot study. J Intern Med. 2021;289(6):906-920.
  25. Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020;14:72-73.
  26. Gatti M, Fusaroli M, Caraceni P, Poluzzi E, De Ponti F, Raschi E. Serious adverse events with tocilizumab: pharmacovigilance as an aid to prioritize monitoring in COVID-19. Br J Clin Pharmacol. 2021;87(3):1533-1540.
  27. Gautret P, Lagier J-C, Parola P, Hoang VT, Meddeb L, Mailhe M et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020;56:105949.
  28. Gautret P, Million M, Jarrot PA, Camoin-Jau L, Colson P, Fenollar F et al. Natural history of COVID-19 and therapeutic options. Expert Rev Clin Immunol. 2020:16(12);1159-1184.
  29. Guan WJ, Liang WH, Zhao Y, Liang HR, Chen ZS, Li YM et al. Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis. Eur Respir J. 2020;55:2000547.
  30. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382:1708-1720.
  31. Guo YR, Cao QD, Hong ZS, Tan YY, Chen SD, Jin HJ et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak – an update on the status. Mil Med Res. 2020;7(1):11.
  32. Hahn KJ, Morales SJ, Lewis JH. Enoxaparin-induced liver injury: case report and review of the literature and FDA adverse event reporting system (FAERS). Drug Saf Case Rep. 2015;2(1):17.
  33. Hendra H, Vajgel G, Antonelou M, Neradova A, Manson B, Clark SG et al. Identifying prognostic risk factors for poor outcome following COVID-19 disease among in-centre haemodialysis patients: role of inflammation and frailty. J Nephrol. 2021;34(2):315-323.
  34. Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L et al. Dexamethasone in hospitalized patients with Covid-19 – preliminary r N Engl J Med. 2021;384(8):693-704.
  35. Ji Dong, Qin E, Xu J, Zhang D, Cheng G, Wang Y et al. Non-alcoholic fatty liver diseases in patients with COVID-19: A retrospective study. J Hepatol. 2020;73:451-453.
  36. Kneeman JM, Misdraji J, Corey KE. Secondary causes of nonalcoholic fatty liver disease. Therap Adv Gastroenterol. 2012;5:199-207.
  37. Kulkarni AV, Kumar P, Tevethia HV, Premkumar M, Arab JP, Candia R et al. Systematic review with meta-analysis: liver manifestations and outcomes in COVID-19. Aliment Pharmacol Ther. 2020;52:584-599.
  38. Le Bert N, Tan AT, Kunasegaran K, Tham CYL, Hafezi M, Chia A et al. SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature. 2020;584:457-462.
  39. Leo M, Ponziani FR, Nesci A, Santoliquido A, Vecchio FM, Francalanci P et al. Low molecular weight heparin as cause of liver injury: case report and literature review. Eur Rev Med Pharmacol Sci. 2019;23:7649-7654.
  40. Li Y, Meng Q, Rao X, Wang B, Zhang X, Dong F et al. Corticosteroid therapy in critically ill patients with COVID-19: a multicenter, retrospective study. Crit Care. 2020;24:698.
  41. LiverTox: Clinical and research information on drug-induced liver injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012. Tocilizumab. [Updated 2020 Apr 18]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548243/
  42. Martinelli I, Ciavarella A, Abbattista M, Aliberti S, De Zan V, Folli C et al. Increasing dosages of low-molecular-weight heparin in hospitalized patients with Covid-19. Intern Emerg Med. 2021;16(5):1223-1229.
  43. Mehershahi S, Mantri N, Kumar A, Danial S, Harish P. Enoxaparin-induced liver i Case Rep Gastroenterol. 2020;14:315-319.
  44. Michaut A, Moreau C, Robin M-A, Fromenty B. Acetaminophen-induced liver injury in obesity and nonalcoholic fatty liver disease. Liver Int. 2014;34:e171-e179.
  45. Mirjalili M, Shafiekhani M, Vazin A. Coronavirus disease 2019 (COVID-19) and transplantation: pharmacotherapeutic management of immunosuppression r Ther Clin Risk Manag. 2020;16:617-629.
  46. Monedero P, Gea A, Castro P, Candela-Toha AM, Hernández-Sanz ML, Arruti E et al. Early corticosteroids are associated with lower mortality in critically ill patients with COVID-19: a cohort study. Crit Care. 2021;25(1):2.
  47. Moores LK, Tritschler T, Brosnahan S, Carrier M, Collen JF, Doerschug K et al. Prevention, diagnosis, and treatment of VTE in patients with coronavirus disease 2019: CHEST guideline and expert panel r Chest. 2020;158:1143-1163.
  48. Nguyen LS, Vautier M, Allenbach Y, Zahr N, Benveniste O, Funck-Brentano C et al. Sirolimus and mTOR inhibitors: a review of side effects and specific management in solid organ transplantation. Drug Safety. 2019;42:813-825.
  49. Primeggia J, Timpone JG, Kumar PN. Pharmacologic issues of antiretroviral agents and immunosuppressive regimens in HIV-infected solid organ transplant recipients. Infect Dis Clin. 2013;27:473-486.
  50. Prysyazhnyuk V, Voloshyn O, Prysiazhniuk I, Ilashchuk T, Sydorchuk L, Prysyazhnyuk P. Glutathione S-transferase T1 and M1 null genotype distribution among non-alcoholic fatty liver disease patients and its association with cytokine and adipokine profiles. Clin Exp Hepatol. 2020;6:142-149.
  51. RECOVERY Collaborative Group, Horby P, Mafham M, Linsell L, Bell JL, Staplin N, Emberson JR et al. Effect of hydroxychloroquine in hospitalized patients with Covid-19. N Engl J Med. 2020;383:2030-2040.
  52. Rentsch CT, Beckman JA, Tomlinson L, Gellad WF, Alcorn C, Kidwai-Khan F et al. Early initiation of prophylactic anticoagulation for prevention of COVID-19 mortality: a nationwide cohort study of hospitalized patients in the United States. medRxiv [Preprint]. 2020:20246579.
  53. Sarzi-Puttini P, D’Ingianna E, Fumagalli M, Scarpellini M, Fiorini T, Chérié-Lignière EL et al. An open, randomized comparison study of cyclosporine A, cyclosporine A+ methotrexate and cyclosporine A+ hydroxychloroquine in the treatment of early severe rheumatoid arthritis. Rheumatol Int. 2005;25:15-22.
  54. Satapathy SK, Kuwajima V, Nadelson J, Atiq O, Sanyal AJ. Drug-induced fatty liver disease: An overview of pathogenesis and management. Ann Hepatol. 2015;14:789-806.
  55. Serviddio G, Villani R, Stallone G, Scioscia G, Foschino-Barbaro MP, Lacedonia D. Tocilizumab and liver injury in patients with COVID-19. Therap Adv Gastroenterol. 2020;13:1-7.
  56. Tortorici MA, Veesler D. Structural insights into coronavirus entry. Adv Virus Res. 2019;105:93-116.
  57. Tur-Kaspa R, Shaul Y, Moore DD, Burk RD, Okret S, Poellinger L et al. The glucocorticoid receptor recognizes a specific nucleotide sequence in hepatitis B virus DNA causing increased activity of the HBV enhancer. Virology. 1988;167:630-633.
  58. Vu CA, DeRonde KJ, Vega AD, Maxam M, Holt G, Natori Y et al. Effects of Tocilizumab in COVID-19 patients: a cohort study. BMC Infect Dis. 2020;20:964.
  59. Wang B, Mufti G, Agarwal K. Reactivation of hepatitis B virus infection in patients with hematologic disorders. Haematologica. 2019;104:435-443.
  60. WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Sterne JAC, Murthy S, Diaz JV, Slutsky AS, Villar J, Angus DC et al. Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis. JAMA. 2020;324:1330-1341.
  61. Clinical management of COVID-19. Available from: https://www.who.int/publications/i/item/clinical-management-of-covid-19.
  62. Corticosteroids for COVID-19. Available from: https://www.who.int/publications/i/item/WHO-2019-nCoV-Corticosteroids-2020.
  63. Yang L, Liu S, Liu J, Zhang Z, Wan X, Huang B et al. COVID-19: immunopathogenesis and immunotherapeutics. Sig Transduct Target Ther. 2020;5:128.
  64. Zhang C, Shi L, Wang FS. Liver injury in COVID-19: management and challenges. Lancet Gastroenterol Hepatol. 2020;5:428-430.