Liver injury in COVID-19: two clinical cases

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COVID-19 (coronavirus disease 2019, a  disease caused by a  new coronavirus 2019) continues to threaten world public healthcare. Epidemiological data indicate that patients with metabolic disorders and chronic illnesses are most susceptible to SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). Potential factors for organ involvement include systemic hyperimmune-mediated inflammation due to the “cytokine storm”, cytopathic effects, hypoxia, drug toxicities, etc. In addition, SARS-CoV-2, by interaction with ACE2 (angiotensin-converting enzyme 2) receptors in the vasculature endothelium results in endothelial dysfunction, increased permeability, microcirculatory abnormalities, vascular thrombophilia and thrombus formation. The diagnosis of COVID-19 is confirmed by detection of SARS-CoV-2 RNA in biological samples and serum antibodies. The infection is associated with leukopenia and thrombocytopenia, increased С-reactive protein, ferritin, lactate dehydrogenase, and D-dimer. Abnormalities in functional liver tests seen in COVID-19 are associated with progression and severity of the infection. The mechanism of direct cytotoxicity due to active SARS-CoV-2 replication in hepatocytes are not fully understood and is likely to be related to potential proliferation of hepatocytes, liver injury in response to systemic inflammation, and development of drug hepatic toxicity. We present a  clinical case of drug-induced hepatitis in a  patient with COVID-19 treated with tocilizumab, an inhibitor of interleukin 6 receptors. Prolonged increase in blood enzymes after treatment cessation is likely related to a  longer half-elimination time of tocilizumab, which affects the oxidation-reduction system of liver cytochromes. Patients with chronic liver disorders are more vulnerable to clinical sequelae of СOVID-19, while the infection is frequently associated with hypoxia and hypoxemia due to severe pneumonia or the “cytokine storm”. In addition, patients who have been diagnosed with liver cirrhosis are at high risk of morbidity and mortality due to their higher proneness to infections, first of all, due to systemic immune deficiency that was demonstrated in the second clinical case. Decompensated liver cirrhosis is related not only to a higher risk of more severe COVID-19, but also to progression of chronic liver disease as such. To achieve effective results of causal and nosotropic therapy for COVID-19, it is highly significant to provide thorough clinical monitoring, tailored approach to the treatment of each patient with consideration of their comorbidities, immune status, and drug interactions.


About the authors

I. G. Nikitin

Pirogov Russian National Research Medical University (RNRMU);
Centre of Medical Rehabilitation

Author for correspondence.
ORCID iD: 0000-0003-1699-0881

Igor G. Nikitin – MD, PhD, Professor, Head of Chair of Hospital Therapy No. 2 Pirogov Russian National Research Medical University (RNRMU); Director Centre of Medical Rehabilitation

1 Ostrovityanova ul., Moscow, 117997; 
3 Ivan'kovskoe shosse, Moscow, 125367

Russian Federation

L. Yu. Ilchenko

Pirogov Russian National Research Medical University (RNRMU);
Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences;
I.I. Mechnikov Scientific Research Institute of Vaccines and Serums

ORCID iD: 0000-0001-6029-1864

Lyudmila Yu. Ilchenko – MD, PhD, Professor, Chair of Hospital Therapy No. 2 Pirogov Russian National Research Medical University (RNRMU); Leading Research Fellow, Laboratory for Modeling Immunobiological Processes Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences; Leading Research Fellow, Laboratory of Viral Hepatitis I.I. Mechnikov Scientific Research Institute of Vaccines and Serums

1 Ostrovityanova ul., Moscow, 117997; 
8–1 Instituta poliomielita poselok, Moskovskiy poselenie, Moscow, 108819; 
5A/1 Malyy Kazennyy pereulok, Moscow, 105064

Russian Federation

I. G. Fedorov

Pirogov Russian National Research Medical University (RNRMU);
Moscow City Clinical Hospital after V.M. Buyanov

ORCID iD: 0000-0003-1003-539X

Ilya G. Fedorov – MD, PhD, Associate Professor, Chair of Hospital Therapy No. 2 Pirogov Russian National Research Medical University (RNRMU); Head of the Gastroenterology Department Moscow City Clinical Hospital after V.M. Buyanov

 1 Ostrovityanova ul., Moscow, 117997; 

26 Bakinskaya ul., Moscow, 115516

Russian Federation

G. G. Totolyan

Pirogov Russian National Research Medical University (RNRMU)

ORCID iD: 0000-0002-9922-5845

Gayane G. Totolyan – MD, PhD, Associate Professor, Chair of Hospital Therapy No. 2 

1 Ostrovityanova ul., Moscow, 117997

Russian Federation


  1. Guarner J. Three emerging coronaviruses in two decades. Am J Clin Pathol. 2020;153(4): 420–1. doi: 10.1093/ajcp/aqaa029.
  2. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu N, Bi Y, Ma X, Zhan F, Wang L, Hu T, Zhou H, Hu Z, Zhou W, Zhao L, Chen J, Meng Y, Wang J, Lin Y, Yuan J, Xie Z, Ma J, Liu WJ, Wang D, Xu W, Holmes EC, Gao GF, Wu G, Chen W, Shi W, Tan W. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395(10224): 565–74. doi: 10.1016/S0140-6736(20)30251-8.
  3. Johns Hopkins University & Medicine. Coronavirus Resource Centre [Internet]. Available from:
  4. Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun. 2020;109:102433. doi: 10.1016/j.jaut.2020.102433.
  5. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, Liu S, Zhao P, Liu H, Zhu L, Tai Y, Bai C, Gao T, Song J, Xia P, Dong J, Zhao J, Wang FS. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420–2. doi: 10.1016/S2213-2600(20)30076-X.
  6. Tai W, He L, Zhang X, Pu J, Voronin D, Jiang S, Zhou Y, Du L. 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(6):613–20. doi: 10.1038/s41423-020-0400-4.
  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):1033–4. doi: 10.1016/S0140-6736(20)30628-0.
  8. Arachchillage DRJ, Laffan M. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18(5): 1233–4. doi: 10.1111/jth.14820.
  9. Centers for Disease Control and Prevention. Coronavirus (COVID-19) [Internet]. Available from:
  10. 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.
  11. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382(18):1708–20. doi: 10.1056/NEJMoa2002032.
  12. Ильченко ЛЮ, Никитин ИГ, Федоров ИГ. COVID-19 и поражение печени. Архивъ внутренней медицины. 2020;10(3):188–97. doi: 10.20514/2226-6704-2020-10-3-188-197.
  13. Young BE, Ong SWX, Kalimuddin S, Low JG, Tan SY, Loh J, Ng OT, Marimuthu K, Ang LW, Mak TM, Lau SK, Anderson DE, Chan KS, Tan TY, Ng TY, Cui L, Said Z, Kurupatham L, Chen MI, Chan M, Vasoo S, Wang LF, Tan BH, Lin RTP, Lee VJM, Leo YS, Lye DC; Singapore 2019 Novel Coronavirus Outbreak Research Team. Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore. JAMA. 2020;323(15):1488–94. doi: 10.1001/jama.2020.3204.
  14. Wander P, Epstein M, Bernstein D. COVID-19 Presenting as Acute Hepatitis. Am J Gastroenterol. 2020;115(6):941–2. doi: 10.14309/ajg.0000000000000660.
  15. Cholankeril G, Podboy A, Aivaliotis VI, Tarlow B, Pham EA, Spencer SP, Kim D, Hsing A, Ahmed A. High prevalence of concurrent gastrointestinal manifestations in patients with severe acute respiratory syndrome coronavirus 2: Early experience from California. Gastroenterology. 2020;159(2):775–7. doi: 10.1053/j.gastro.2020.04.008.
  16. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–13. doi: 10.1016/S0140-6736(20)30211-7.
  17. Hanley B, Lucas SB, Youd E, Swift B, Osborn M. Autopsy in suspected COVID-19 cases. J Clin Pathol. 2020;73(5):239–42. doi: 10.1136/jclinpath-2020-206522.
  18. Министерство здравоохранения Российской Федерации. Временные методические рекомендации: профилактика, диагностика и лечение новой коронавирусной инфекции (COVID-19) [Интернет]. Версия 8.1 (01.10.2020). Доступно на:
  19. Левитова ДГ, Грачева СА, Самойлов АС, Удалов ЮД, Праскурничий ЕА, Паринов ОВ. Вопросы безопасности лекарственной терапии COVID-19. Архивъ внутренней медицины. 2020;10(3):165–87. doi: 10.20514/2226-6704-2020-10-3-165-187.
  20. Flaig T, Douros A, Bronder E, Klimpel A, Kreutz R, Garbe E. Tocilizumab-induced pancreatitis: case report and review of data from the FDA Adverse Event Reporting System. J Clin Pharm Ther. 2016;41(6):718–21. doi: 10.1111/jcpt.12456.
  21. Gout T, Ostör AJ, Nisar MK. Lower gastrointestinal perforation in rheumatoid arthritis patients treated with conventional DMARDs or tocilizumab: a systematic literature review. Clin Rheumatol. 2011;30(11):1471–4. doi: 10.1007/s10067-011-1827-x.
  22. Xie F, Yun H, Bernatsky S, Curtis JR. Brief Report: Risk of Gastrointestinal Perforation Among Rheumatoid Arthritis Patients Receiving Tofacitinib, Tocilizumab, or Other Biologic Treatments. Arthritis Rheumatol. 2016;68(11): 2612–7. doi: 10.1002/art.39761.
  23. SIMIT – Italian Society of Infectious and Tropical Diseases. Handbook for the care of people with disease-COVID 19. Section of Regione Lombardia. Edition 2.0, March 13, 2020 [Internet]. Available from:
  24. Evaluating the drug-drug interaction risk of experimental COVID-19 therapies [Internet]. Available from:
  25. Ji D, Qin E, Xu J, Zhang D, Cheng G, Wang Y, Lau G. Non-alcoholic fatty liver diseases in patients with COVID-19: A retrospective study. J Hepatol. 2020;73(2):451–3. doi: 10.1016/j.jhep.2020.03.044.
  26. Boettler T, Newsome PN, Mondelli MU, Maticic M, Cordero E, Cornberg M, Berg T. Care of patients with liver disease during the COVID-19 pandemic: EASL-ESCMID position paper. JHEP Rep. 2020;2(3):100113. doi: 10.1016/j.jhepr.2020.100113.
  27. Lleo A, Invernizzi P, Lohse AW, Aghemo A, Carbone M. Management of patients with autoimmune liver disease during COVID-19 pandemic. J Hepatol. 2020;73(2):453–5. doi: 10.1016/j.jhep.2020.04.002.
  28. Tapper EB, Asrani SK. The COVID-19 pandemic will have a long-lasting impact on the quality of cirrhosis care. J Hepatol. 2020;73(2):441–5. doi: 10.1016/j.jhep.2020.04.005.
  29. Saigal S, Gupta S, Sudhindran S, Goyal N, Rastogi A, Jacob M, Raja K, Ramamurthy A, Asthana S, Dhiman RK, Singh B, Perumalla R, Malik A, Shanmugham N, Soin AS. Liver transplantation and COVID-19 (Coronavirus) infection: guidelines of the liver transplant Society of India (LTSI). Hepatol Int. 2020;14(4):429–31. doi: 10.1007/s12072-020-10041-1.
  30. Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. Evidence for Gastrointestinal Infection of SARSCoV-2. Gastroenterology. 2020;158(6):1831–3. e3. doi: 10.1053/j.gastro.2020.02.055.
  31. Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, Wang T, Zhang X, Chen H, Yu H, Zhang X, Zhang M, Wu S, Song J, Chen T, Han M, Li S, Luo X, Zhao J, Ning Q. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020;130(5): 2620–9. doi: 10.1172/JCI137244.
  32. Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, Xie C, Ma K, Shang K, Wang W, Tian DS. Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 2020;71(15):762–8. doi: 10.1093/cid/ciaa248.
  33. Xiao Y, Pan H, She Q, Wang F, Chen M. Prevention of SARS-CoV-2 infection in patients with decompensated cirrhosis. Lancet Gastroenterol Hepatol. 2020;5(6):528–9. doi: 10.1016/S2468-1253(20)30080-7.
  34. Данные о смертности от коронавируса [Интернет]. Доступно на:
  35. Sorbello M, El-Boghdadly K, Di Giacinto I, Cataldo R, Esposito C, Falcetta S, Merli G, Cortese G, Corso RM, Bressan F, Pintaudi S, Greif R, Donati A, Petrini F; Società Italiana di Anestesia Analgesia Rianimazione e Terapia Intensiva (SIAARTI) Airway Research Group, and The European Airway Management Society. The Italian coronavirus disease 2019 outbreak: recommendations from clinical practice. Anaesthesia. 2020;75(6):724–32. doi: 10.1111/anae.15049.
  36. Bhimraj A, Morgan RL, Shumaker AH, Lavergne V, Baden L, Cheng VC, Edwards KM, Gandhi R, Muller WJ, O'Horo JC, Shoham S, Murad MH, Mustafa RA, Sultan S, Falck-Ytter Y. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. Clin Infect Dis. 2020:ciaa478. doi: 10.1093/cid/ciaa478.
  37. Helms J, Kremer S, Merdji H, Clere-Jehl R, Schenck M, Kummerlen C, Collange O, Boulay C, Fafi-Kremer S, Ohana M, Anheim M, Meziani F. Neurologic Features in Severe SARSCoV-2 Infection. N Engl J Med. 2020;382(23): 2268–70. doi: 10.1056/NEJMc2008597.
  38. Cheema M, Aghazadeh H, Nazarali S, Ting A, Hodges J, McFarlane A, Kanji JN, Zelyas N, Damji KF, Solarte C. Keratoconjunctivitis as the initial medical presentation of the novel coronavirus disease 2019 (COVID-19). Can J Ophthalmol. 2020;55(4):e125–9. doi: 10.1016/j.jcjo.2020.03.003.
  39. Galván Casas C, Català A, Carretero Hernández G, Rodríguez-Jiménez P, Fernández-Nieto D, Rodríguez-Villa Lario A, Navarro Fernández I, Ruiz-Villaverde R, Falkenhain-López D, Llamas Velasco M, García-Gavín J, Baniandrés O, González-Cruz C, Morillas-Lahuerta V, Cubiró X, Figueras Nart I, Selda-Enriquez G, Romaní J, Fustà-Novell X, Melian-Olivera A, Roncero Riesco M, Burgos-Blasco P, Sola Ortigosa J, Feito Rodriguez M, García-Doval I. Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases. Br J Dermatol. 2020;183(1):71–7. doi: 10.1111/bjd.19163.
  40. Wang F, Wang H, Fan J, Zhang Y, Wang H, Zhao Q. Pancreatic injury patterns in patients with Coronavirus disease 19 pneumonia. Gastroenterology. 2020;159(1):367–70. doi: 10.1053/j.gastro.2020.03.055.
  41. Tapper EB, Asrani SK. The COVID-19 pandemic will have a long-lasting impact on the quality of cirrhosis care. J Hepatol. 2020;73(2):441–5. doi: 10.1016/j.jhep.2020.04.005.
  42. The COVID-Hep registry [Internet]. Available from:

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Copyright (c) 2020 Nikitin I.G., Ilchenko L.Y., Fedorov I.G., Totolyan G.G.

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