Semin Liver Dis 2023; 43(03): 351-366
DOI: 10.1055/a-2157-3318
Review Article

COVID-19 and Liver Disease: An Evolving Landscape

Kai Zhu
1   Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
,
Olivia Tsai
1   Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
,
Daljeet Chahal
2   Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia, Canada
3   BC Liver Transplant Program, Vancouver, British Columbia, Canada
,
Trana Hussaini
3   BC Liver Transplant Program, Vancouver, British Columbia, Canada
4   Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada
,
Eric M. Yoshida
2   Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia, Canada
3   BC Liver Transplant Program, Vancouver, British Columbia, Canada
› Author Affiliations
Funding None.


Abstract

The COVID-19 pandemic has resulted in significant worldwide morbidity and mortality. In this review, we examine the intricate relationships between COVID-19 and liver diseases. While respiratory manifestations of COVID-19 are well known, its impact and consequences in patients with liver diseases remain an area of ongoing investigation. COVID-19 can induce liver injury through various mechanisms and is associated with higher mortality in individuals with preexisting chronic liver disease. Mortality increases with the severity of chronic liver disease and the level of care required. The outcomes in patients with autoimmune hepatitis remain unclear, whereas liver transplant recipients are more likely to experience symptomatic COVID-19 but have comparable outcomes to the general population. Despite suboptimal immunological response, COVID-19 vaccinations are safe and effective in liver disease, although cases of autoimmune hepatitis-like syndrome have been reported. In conclusion, COVID-19 has significant implications in liver diseases; early recognition and treatments are important for improving patient outcomes.



Publication History

Accepted Manuscript online:
21 August 2023

Article published online:
29 September 2023

© 2023. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 
  • References

  • 1 Guan WJ, Ni ZY, Hu Y. et al; China Medical Treatment Expert Group for COVID-19. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020; 382 (18) 1708-1720
  • 2 Sultan S, Altayar O, Siddique SM. et al; AGA Institute. Electronic address: ewilson@gastro.org. AGA Institute Rapid Review of the gastrointestinal and liver manifestations of COVID-19, meta-analysis of international data, and recommendations for the consultative management of patients with COVID-19. Gastroenterology 2020; 159 (01) 320-334.e27
  • 3 Richardson S, Hirsch JS, Narasimhan M. et al; The Northwell COVID-19 Research Consortium. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area. JAMA 2020; 323 (20) 2052-2059
  • 4 Goyal P, Choi JJ, Pinheiro LC. et al. Clinical characteristics of COVID-19 in New York City. N Engl J Med 2020; 382 (24) 2372-2374
  • 5 Hundt MA, Deng Y, Ciarleglio MM, Nathanson MH, Lim JK. Abnormal liver tests in COVID-19: a retrospective observational cohort study of 1,827 patients in a major U.S. hospital network. Hepatology 2020; 72 (04) 1169-1176
  • 6 Fu Y, Zhu R, Bai T. et al. Clinical features of patients infected with coronavirus disease 2019 with elevated liver biochemistries: a multicenter, retrospective study. Hepatology 2021; 73 (04) 1509-1520
  • 7 Phipps MM, Barraza LH, LaSota ED. et al. Acute liver injury in COVID-19: prevalence and association with clinical outcomes in a large U.S. cohort. Hepatology 2020; 72 (03) 807-817
  • 8 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
  • 9 Giacomelli A, Ridolfo AL, Milazzo L. et al. 30-day mortality in patients hospitalized with COVID-19 during the first wave of the Italian epidemic: a prospective cohort study. Pharmacol Res 2020; 158: 104931
  • 10 Bzeizi K, Abdulla M, Mohammed N, Alqamish J, Jamshidi N, Broering D. Effect of COVID-19 on liver abnormalities: a systematic review and meta-analysis. Sci Rep 2021; 11 (01) 10599
  • 11 Huang J, Cheng A, Kumar R. et al. Hypoalbuminemia predicts the outcome of COVID-19 independent of age and co-morbidity. J Med Virol 2020; 92 (10) 2152-2158
  • 12 Aziz M, Fatima R, Lee-Smith W, Assaly R. The association of low serum albumin level with severe COVID-19: a systematic review and meta-analysis. Crit Care 2020; 24 (01) 255
  • 13 Arroyo V, García-Martinez R, Salvatella X. Human serum albumin, systemic inflammation, and cirrhosis. J Hepatol 2014; 61 (02) 396-407
  • 14 Wu MA, Fossali T, Pandolfi L. et al. Hypoalbuminemia in COVID-19: assessing the hypothesis for underlying pulmonary capillary leakage. J Intern Med 2021; 289 (06) 861-872
  • 15 Fleck A, Raines G, Hawker F. et al. Increased vascular permeability: a major cause of hypoalbuminaemia in disease and injury. Lancet 1985; 1 (8432) 781-784
  • 16 Altomare A, Baron G, Brioschi M. et al. N-Acetyl-cysteine regenerates albumin Cys34 by a thiol-disulfide breaking mechanism: an explanation of its extracellular antioxidant activity. Antioxidants 2020; 9 (05) 367
  • 17 Violi F, Ceccarelli G, Loffredo L. et al. Albumin supplementation dampens hypercoagulability in COVID-19: a preliminary report. Thromb Haemost 2021; 121 (01) 102-105
  • 18 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
  • 19 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 (04) 807-816
  • 20 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 (09) 2110-2116
  • 21 Massoth LR, Desai N, Szabolcs A. et al. Comparison of RNA in situ hybridization and immunohistochemistry techniques for the detection and localization of SARS-CoV-2 in human tissues. Am J Surg Pathol 2021; 45 (01) 14-24
  • 22 Pirola CJ, Sookoian S. SARS-CoV-2 virus and liver expression of host receptors: putative mechanisms of liver involvement in COVID-19. Liver Int 2020; 40 (08) 2038-2040
  • 23 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
  • 24 Chai X, Hu L, Zhang Y. et al. Specific ACE2 expression in cholangiocytes may cause liver damage after 2019-nCoV infection. bioRxiv DOI: 10.1101/2020.02.03.931766.
  • 25 Chen J, Subbarao K. The immunobiology of SARS*. Annu Rev Immunol 2007; 25: 443-472
  • 26 Fan Z, Chen L, Li J. et al. Clinical features of COVID-19-related liver functional abnormality. Clin Gastroenterol Hepatol 2020; 18 (07) 1561-1566
  • 27 Ji D, Qin E, Xu J. et al. Non-alcoholic fatty liver diseases in patients with COVID-19: a retrospective study. J Hepatol 2020; 73 (02) 451-453
  • 28 Effenberger M, Grander C, Grabherr F. et al. Systemic inflammation as fuel for acute liver injury in COVID-19. Dig Liver Dis 2021; 53 (02) 158-165
  • 29 McConnell MJ, Kawaguchi N, Kondo R. et al. Liver injury in COVID-19 and IL-6 trans-signaling-induced endotheliopathy. J Hepatol 2021; 75 (03) 647-658
  • 30 Zhu J, Pang J, Ji P. et al. Elevated interleukin-6 is associated with severity of COVID-19: a meta-analysis. J Med Virol 2021; 93 (01) 35-37
  • 31 Wichmann D, Sperhake JP, Lütgehetmann M. et al. Autopsy findings and venous thromboembolism in patients with COVID-19: a prospective cohort study. Ann Intern Med 2020; 173 (04) 268-277
  • 32 Rapkiewicz AV, Mai X, Carsons SE. et al. Megakaryocytes and platelet-fibrin thrombi characterize multi-organ thrombosis at autopsy in COVID-19: a case series. EClinicalMedicine 2020; 24: 100434
  • 33 Wang XX, Shao C, Huang XJ. et al. Histopathological features of multiorgan percutaneous tissue core biopsy in patients with COVID-19. J Clin Pathol 2021; 74 (08) 522-527
  • 34 Zampino R, Mele F, Florio LL. et al. Liver injury in remdesivir-treated COVID-19 patients. Hepatol Int 2020; 14 (05) 881-883
  • 35 Muhović D, Bojović J, Bulatović A. et al. First case of drug-induced liver injury associated with the use of tocilizumab in a patient with COVID-19. Liver Int 2020; 40 (08) 1901-1905
  • 36 Marjot T, Webb GJ, Barritt IV AS. et al. COVID-19 and liver disease: mechanistic and clinical perspectives. Nat Rev Gastroenterol Hepatol 2021; 18 (05) 348-364
  • 37 Soriano JB, Murthy S, Marshall JC, Relan P, Diaz JV. WHO Clinical Case Definition Working Group on Post-COVID-19 Condition. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis 2022; 22 (04) e102-e107
  • 38 O'Mahoney LL, Routen A, Gillies C. et al. The prevalence and long-term health effects of long COVID among hospitalised and non-hospitalised populations: a systematic review and meta-analysis. EClinicalMedicine 2022; 55: 101762
  • 39 de Lima IC, de Menezes DC, Uesugi JHE. et al. Liver function in patients with long-term coronavirus disease 2019 of up to 20 months: a cross-sectional study. Int J Environ Res Public Health 2023; 20 (07) 5281
  • 40 Bende F, Tudoran C, Sporea I. et al. A multidisciplinary approach to evaluate the presence of hepatic and cardiac abnormalities in patients with post-acute COVID-19 syndrome - a pilot study. J Clin Med 2021; 10 (11) 2507
  • 41 Milic J, Barbieri S, Gozzi L. et al. Metabolic-associated fatty liver disease is highly prevalent in the postacute COVID syndrome. Open Forum Infect Dis 2022; 9 (03) ofac003
  • 42 Phetsouphanh C, Darley DR, Wilson DB. et al. Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection. Nat Immunol 2022; 23 (02) 210-216
  • 43 Huby T, Gautier EL. Immune cell-mediated features of non-alcoholic steatohepatitis. Nat Rev Immunol 2022; 22 (07) 429-443
  • 44 Xu Z, Shi L, Wang Y. et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020; 8 (04) 420-422
  • 45 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
  • 46 Williamson EJ, Walker AJ, Bhaskaran K. et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature 2020; 584 (7821) 430-436
  • 47 Zhang B, Huang W, Zhang S. Clinical features and outcomes of coronavirus disease 2019 (COVID-19) patients with chronic hepatitis B virus infection. Clin Gastroenterol Hepatol 2020; 18 (11) 2633-2637
  • 48 Li Y, Li C, Wang J. et al. A case series of COVID-19 patients with chronic hepatitis B virus infection. J Med Virol 2020; 92 (11) 2785-2791
  • 49 Mangia A, Cenderello G, Verucchi G. et al. Is positivity for hepatitis C virus antibody predictive of lower risk of death in COVID-19 patients with cirrhosis?. World J Clin Cases 2020; 8 (22) 5831-5834
  • 50 Weinreich DM, Sivapalasingam S, Norton T. et al; Trial Investigators. REGEN-COV antibody combination and outcomes in outpatients with COVID-19. N Engl J Med 2021; 385 (23) e81
  • 51 Bajaj JS, Garcia-Tsao G, Biggins SW. et al. Comparison of mortality risk in patients with cirrhosis and COVID-19 compared with patients with cirrhosis alone and COVID-19 alone: multicentre matched cohort. Gut 2021; 70 (03) 531-536
  • 52 Singh S, Khan A. Clinical characteristics and outcomes of coronavirus disease 2019 among patients with preexisting liver disease in the United States: a multicenter research network study. Gastroenterology 2020; 159 (02) 768-771.e3
  • 53 Huang R, Zhu L, Wang J. et al. Clinical features of patients with COVID-19 with nonalcoholic fatty liver disease. Hepatol Commun 2020; 4 (12) 1758-1768
  • 54 Sharma P, Kumar A. Metabolic dysfunction associated fatty liver disease increases risk of severe COVID-19. Diabetes Metab Syndr 2020; 14 (05) 825-827
  • 55 Dongiovanni P, Meroni M, Longo M, Fracanzani AL. MAFLD in COVID-19 patients: an insidious enemy. Expert Rev Gastroenterol Hepatol 2020; 14 (10) 867-872
  • 56 Kazankov K, Jørgensen SMD, Thomsen KL. et al. The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Nat Rev Gastroenterol Hepatol 2019; 16 (03) 145-159
  • 57 Denson JL, Gillet AS, Zu Y. et al; Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group. Metabolic syndrome and acute respiratory distress syndrome in hospitalized patients with COVID-19. JAMA Netw Open 2021; 4 (12) e2140568-e2140568
  • 58 Marjot T, Moon AM, Cook JA. et al. Outcomes following SARS-CoV-2 infection in patients with chronic liver disease: an international registry study. J Hepatol 2021; 74 (03) 567-577
  • 59 Toussirot E, Roudier J. Epstein-Barr virus in autoimmune diseases. Best Pract Res Clin Rheumatol 2008; 22 (05) 883-896
  • 60 Zandman-Goddard G, Shoenfeld Y. HIV and autoimmunity. Autoimmun Rev 2002; 1 (06) 329-337
  • 61 Halenius A, Hengel H. Human cytomegalovirus and autoimmune disease. BioMed Res Int 2014; 472978
  • 62 Novelli L, Motta F, De Santis M, Ansari AA, Gershwin ME, Selmi C. The JANUS of chronic inflammatory and autoimmune diseases onset during COVID-19 - a systematic review of the literature. J Autoimmun 2021; 117: 102592
  • 63 Chang R, Yen-Ting Chen T, Wang S-I, Hung Y-M, Chen H-Y, Wei CJ. Risk of autoimmune diseases in patients with COVID-19: a retrospective cohort study. EClinicalMedicine 2023; 56: 101783
  • 64 Smatti MK, Cyprian FS, Nasrallah GK, Al Thani AA, Almishal RO, Yassine HM. Viruses and autoimmunity: a review on the potential interaction and molecular mechanisms. Viruses 2019; 11 (08) 762
  • 65 Dotan A, Muller S, Kanduc D, David P, Halpert G, Shoenfeld Y. The SARS-CoV-2 as an instrumental trigger of autoimmunity. Autoimmun Rev 2021; 20 (04) 102792
  • 66 Wang J, Jiang M, Chen X, Montaner LJ. Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts. J Leukoc Biol 2020; 108 (01) 17-41
  • 67 Qin C, Zhou L, Hu Z. et al. Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis 2020; 71 (15) 762-768
  • 68 Narasaraju T, Tang BM, Herrmann M, Muller S, Chow VTK, Radic M. Neutrophilia and NETopathy as key pathologic drivers of progressive lung impairment in patients with COVID-19. Front Pharmacol 2020; 11: 870
  • 69 Tomar B, Anders HJ, Desai J, Mulay SR. Neutrophils and neutrophil extracellular traps drive necroinflammation in COVID-19. Cells 2020; 9 (06) 1383
  • 70 Kanduc D, Shoenfeld Y. Molecular mimicry between SARS-CoV-2 spike glycoprotein and mammalian proteomes: implications for the vaccine. Immunol Res 2020; 68 (05) 310-313
  • 71 Hong J, Chopra S, Kahn J. et al. Autoimmune hepatitis triggered by COVID-19. Intern Med J 2021; 51 (07) 1182-1183
  • 72 Kulkarni AV, Vasireddy S, Sharma M, Reddy ND, Padaki NR. COVID-19 masquerading as autoimmune hepatitis (AIH) flare - the first report. J Clin Exp Hepatol 2022; 12 (01) 241-243
  • 73 Kabaçam G, Wahlin S, Efe C. Autoimmune hepatitis triggered by COVID-19: a report of two cases. Liver Int 2021; 41 (10) 2527-2528
  • 74 Grainger R, Kim AHJ, Conway R, Yazdany J, Robinson PC. COVID-19 in people with rheumatic diseases: risks, outcomes, treatment considerations. Nat Rev Rheumatol 2022; 18 (04) 191-204
  • 75 Lin S, Lau LHS, Chanchlani N, Kennedy NA, Ng SC. Recent advances in clinical practice: management of inflammatory bowel disease during the COVID-19 pandemic. Gut 2022; 71 (07) 1426-1439
  • 76 Webb GJ, Marjot T, Cook JA. et al. Outcomes following SARS-CoV-2 infection in liver transplant recipients: an international registry study. Lancet Gastroenterol Hepatol 2020; 5 (11) 1008-1016
  • 77 Ravanan R, Callaghan CJ, Mumford L. et al. SARS-CoV-2 infection and early mortality of waitlisted and solid organ transplant recipients in England: a national cohort study. Am J Transplant 2020; 20 (11) 3008-3018
  • 78 Gerussi A, Rigamonti C, Elia C. et al. Coronavirus disease 2019 in autoimmune hepatitis: a lesson from immunosuppressed patients. Hepatol Commun 2020; 4 (09) 1257-1262
  • 79 Marjot T, Buescher G, Sebode M. et al; Contributing Members and Collaborators of ERN RARE-LIVER/COVID-Hep/SECURE-Cirrhosis. SARS-CoV-2 infection in patients with autoimmune hepatitis. J Hepatol 2021; 74 (06) 1335-1343
  • 80 Efe C, Dhanasekaran R, Lammert C. et al. Outcome of COVID-19 in patients with autoimmune hepatitis: an international multicenter study. Hepatology 2021; 73 (06) 2099-2109
  • 81 Efe C, Lammert C, Taşçılar K. et al. Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis. Liver Int 2022; 42 (03) 607-614
  • 82 Fix O, Hameed B, Fontana R. et al. Clinical best practice advice for hepatology and liver transplant providers during the COVID-19 pandemic: AASLD expert panel consensus statement. Hepatology 2020; 72 (01) 287-304
  • 83 Trapani S, Masiero L, Puoti F. et al; Italian Network of Regional Transplant Coordinating Centers Collaborating group, Italian Surveillance System of COVID-19, Italian Society for Organ Transplantation (SITO), The Italian Board of Experts in Liver Transplantation (I-BELT) Study Group, Italian Association for the Study of the Liver (AISF), Italian Society of Nephrology (SIN), SIN-SITO Study Group. Incidence and outcome of SARS-CoV-2 infection on solid organ transplantation recipients: a nationwide population-based study. Am J Transplant 2021; 21 (07) 2509-2521
  • 84 Pereira MR, Mohan S, Cohen DJ. et al. COVID-19 in solid organ transplant recipients: initial report from the US epicenter. Am J Transplant 2020; 20 (07) 1800-1808
  • 85 Fernández-Ruiz M, Andrés A, Loinaz C. et al. COVID-19 in solid organ transplant recipients: a single-center case series from Spain. Am J Transplant 2020; 20 (07) 1849-1858
  • 86 Colmenero J, Rodríguez-Perálvarez M, Salcedo M. et al. Epidemiological pattern, incidence, and outcomes of COVID-19 in liver transplant patients. J Hepatol 2021; 74 (01) 148-155
  • 87 Guarino M, Cossiga V, Loperto I. et al. COVID-19 in liver transplant recipients: incidence, hospitalization and outcome in an Italian prospective double-centre study. Sci Rep 2022; 12 (01) 4831
  • 88 Verma A, Khorsandi SE, Dolcet A. et al. Low prevalence and disease severity of COVID-19 in post-liver transplant recipients - a single centre experience. Liver Int 2020; 40 (08) 1972-1976
  • 89 Akdur A, Karakaya E, Ayvazoglu Soy EH. et al. Coronavirus disease (COVID-19) in kidney and liver transplant patients: a single-center experience. Exp Clin Transplant 2020; 18 (03) 270-274
  • 90 Romagnoli R, Gruttadauria S, Tisone G. et al. Liver transplantation from active COVID-19 donors: a lifesaving opportunity worth grasping?. Am J Transplant 2021; 21 (12) 3919-3925
  • 91 Kidson KM, Park J, Charles MK. et al. Successful liver transplantation in a patient with acute COVID-19 infection and acute liver failure: a case report. Transplant Direct 2021; 7 (10) e747
  • 92 Yohanathan L, Campioli CC, Mousa OY. et al. Liver transplantation for acute liver failure in a SARS-CoV-2 PCR-positive patient. Am J Transplant 2021; 21 (08) 2890-2894
  • 93 Kulkarni AV, Tevethia HV, Premkumar M. et al. Impact of COVID-19 on liver transplant recipients - a systematic review and meta-analysis. EClinicalMedicine 2021; 38: 101025
  • 94 COVID-19 Map - Johns Hopkins Coronavirus Resource Center. Accessed May 23, 2023, at: https://coronavirus.jhu.edu/map.html
  • 95 Smith MK, Chow J, Huang R. et al. COVID-19 infection in liver transplant recipients: clinical features and outcomes from a Canadian multicentre cohort. Can Liver J 2022; 5 (04) 507-512
  • 96 Abani O, Abbas A, Abbas F. et al; RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 2021; 397 (10285): 1637-1645
  • 97 Horby P, Lim WS, Emberson JR. et al; RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with COVID-19. N Engl J Med 2021; 384 (08) 693-704
  • 98 Belli LS, Fondevila C, Cortesi PA. et al; ELITA-ELTR COVID-19 Registry. 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 (04) 1151-1163.e3
  • 99 Yadav DK, Adhikari VP, Ling Q, Liang T. Immunosuppressants in liver transplant recipients with coronavirus disease 2019: capability or catastrophe?—a systematic review and meta-analysis. Front Med 2021; 8: 756922
  • 100 Albillos A, Lario M, Álvarez-Mon M. Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance. J Hepatol 2014; 61 (06) 1385-1396
  • 101 Leise MD, Talwalkar JA. Immunizations in chronic liver disease: what should be done and what is the evidence. Curr Gastroenterol Rep 2013; 15 (01) 300
  • 102 Schinas G, Polyzou E, Mitropetrou F. et al. COVID-19 vaccination in patients with chronic liver disease. Viruses 2022; 14 (12) 2778
  • 103 Ai J, Wang J, Liu D. et al. Safety and immunogenicity of SARS-CoV-2 vaccines in patients with chronic liver diseases (CHESS-NMCID 2101): a multicenter study. Clin Gastroenterol Hepatol 2022; 20 (07) 1516-1524.e2
  • 104 Wang J, Zhang Q, Ai J. et al. Safety and immunogenicity of SARS-CoV-2 vaccines in Chinese patients with cirrhosis: a prospective multicenter study. Hepatol Int 2022; 16 (03) 691-701
  • 105 Ruether DF, Schaub GM, Duengelhoef PM. et al. SARS-CoV2-specific humoral and T-cell immune response after second vaccination in liver cirrhosis and transplant patients. Clin Gastroenterol Hepatol 2022; 20 (01) 162-172.e9
  • 106 Thuluvath PJ, Robarts P, Chauhan M. Analysis of antibody responses after COVID-19 vaccination in liver transplant recipients and those with chronic liver diseases. J Hepatol 2021; 75 (06) 1434-1439
  • 107 Giambra V, Piazzolla AV, Cocomazzi G. et al. Effectiveness of booster dose of anti SARS-CoV-2 BNT162b2 in cirrhosis: longitudinal evaluation of humoral and cellular response. Vaccines (Basel) 2022; 10 (08) 1281
  • 108 Bakasis AD, Bitzogli K, Mouziouras D. et al. Antibody responses after SARS-CoV-2 vaccination in patients with liver diseases. Viruses 2022; 14 (02) 207
  • 109 Willuweit K, Frey A, Passenberg M. et al. Patients with liver cirrhosis show high immunogenicity upon COVID-19 vaccination but develop premature deterioration of antibody titers. Vaccines (Basel) 2022; 10 (03) 377
  • 110 Simão AL, Palma CS, Izquierdo-Sanchez L. et al. Cirrhosis is associated with lower serological responses to COVID-19 vaccines in patients with chronic liver disease. JHEP Rep Innov Hepatol 2023; 5 (05) 100697
  • 111 John BV, Ferreira RD, Doshi A. et al. Third dose of COVID-19 mRNA vaccine appears to overcome vaccine hyporesponsiveness in patients with cirrhosis. J Hepatol 2022; 77 (05) 1349-1358
  • 112 Wang J, Hou Z, Liu J. et al. Safety and immunogenicity of COVID-19 vaccination in patients with non-alcoholic fatty liver disease (CHESS2101): a multicenter study. J Hepatol 2021; 75 (02) 439-441
  • 113 He T, Zhou Y, Xu P. et al. Safety and antibody response to inactivated COVID-19 vaccine in patients with chronic hepatitis B virus infection. Liver Int 2022; 42 (06) 1287-1296
  • 114 Xiang T, Liang B, Wang H. et al. Safety and immunogenicity of a SARS-CoV-2 inactivated vaccine in patients with chronic hepatitis B virus infection. Cell Mol Immunol 2021; 18 (12) 2679-2681
  • 115 Efe C, Kulkarni AV, Terziroli Beretta-Piccoli B. et al. Liver injury after SARS-CoV-2 vaccination: features of immune-mediated hepatitis, role of corticosteroid therapy and outcome. Hepatology 2022; 76 (06) 1576-1586
  • 116 Albillos A, Martin-Mateos R, Van der Merwe S, Wiest R, Jalan R, Álvarez-Mon M. Cirrhosis-associated immune dysfunction. Nat Rev Gastroenterol Hepatol 2022; 19 (02) 112-134
  • 117 Guarino M, Esposito I, Portella G. et al; UniNa Collaborating Group. Humoral response to 2-dose BNT162b2 mRNA COVID-19 vaccination in liver transplant recipients. Clin Gastroenterol Hepatol 2022; 20 (07) 1534-1541.e4
  • 118 Toniutto P, Falleti E, Cmet S. et al. Past COVID-19 and immunosuppressive regimens affect the long-term response to anti-SARS-CoV-2 vaccination in liver transplant recipients. J Hepatol 2022; 77 (01) 152-162
  • 119 Timmermann L, Globke B, Lurje G. et al. Humoral immune response following SARS-CoV-2 vaccination in liver transplant recipients. Vaccines (Basel) 2021; 9 (12) 1422
  • 120 Rashidi-Alavijeh J, Frey A, Passenberg M. et al. Humoral response to SARS-CoV-2 vaccination in liver transplant recipients - a single-center experience. Vaccines (Basel) 2021; 9 (07) 738
  • 121 Rabinowich L, Grupper A, Baruch R. et al. Low immunogenicity to SARS-CoV-2 vaccination among liver transplant recipients. J Hepatol 2021; 75 (02) 435-438
  • 122 Benotmane I, Gautier G, Perrin P. et al. Antibody response after a third dose of the mRNA-1273 SARS-CoV-2 vaccine in kidney transplant recipients with minimal serologic response to 2 doses. JAMA 2021; 326 (11) 1063-1065
  • 123 Narasimhan M, Mahimainathan L, Clark AE. et al. Serological response in lung transplant recipients after two doses of SARS-CoV-2 mRNA vaccines. Vaccines (Basel) 2021; 9 (07) 708
  • 124 Redjoul R, Le Bouter A, Beckerich F, Fourati S, Maury S. Antibody response after second BNT162b2 dose in allogeneic HSCT recipients. Lancet 2021; 398 (10297): 298-299
  • 125 Danziger-Isakov L, Kumar D. AST ID Community of Practice. Vaccination of solid organ transplant candidates and recipients: guidelines from the American society of transplantation infectious diseases community of practice. Clin Transplant 2019; 33 (09) e13563
  • 126 John BV, Deng Y, Scheinberg A. et al. Association of BNT162b2 mRNA and mRNA-1273 vaccines with COVID-19 infection and hospitalization among patients with cirrhosis. JAMA Intern Med 2021; 181 (10) 1306-1314
  • 127 Ge J, Digitale JC, Pletcher MJ, Lai JC. N3C Consortium. Breakthrough SARS-CoV-2 infection outcomes in vaccinated patients with chronic liver disease and cirrhosis: a national COVID cohort collaborative study. Hepatology 2023; 77 (03) 834-850
  • 128 Aslam S, Adler E, Mekeel K, Little SJ. Clinical effectiveness of COVID-19 vaccination in solid organ transplant recipients. Transpl Infect Dis 2021; 23 (05) e13705
  • 129 Moon AM, Webb GJ, García-Juárez I. et al. SARS-CoV-2 infections among patients with liver disease and liver transplantation who received COVID-19 vaccination. Hepatol Commun 2022; 6 (04) 889-897
  • 130 Selected Adverse Events Reported after COVID-19 Vaccination | CDC. Accessed May 22, 2023, at: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/adverse-events.html
  • 131 Cheung KS, Mok CH, Mao X. et al. COVID-19 vaccine immunogenicity among chronic liver disease patients and liver transplant recipients: a meta-analysis. Clin Mol Hepatol 2022; 28 (04) 890-911
  • 132 Wong CKH, Mak LY, Au ICH. et al. Risk of acute liver injury following the mRNA (BNT162b2) and inactivated (CoronaVac) COVID-19 vaccines. J Hepatol 2022; 77 (05) 1339-1348
  • 133 Vojdani A, Kharrazian D. Potential antigenic cross-reactivity between SARS-CoV-2 and human tissue with a possible link to an increase in autoimmune diseases. Clin Immunol 2020; 217: 108480
  • 134 Schinas G, Polyzou E, Dimakopoulou V, Tsoupra S, Gogos C, Akinosoglou K. Immune-mediated liver injury following COVID-19 vaccination. World J Virol 2023; 12 (02) 100-108
  • 135 Kumar D, Tandon RK. Use of ursodeoxycholic acid in liver diseases. J Gastroenterol Hepatol 2001; 16 (01) 3-14
  • 136 Rudic JS, Poropat G, Krstic MN, Bjelakovic G, Gluud C. Ursodeoxycholic acid for primary biliary cirrhosis. Cochrane Database Syst Rev 2012; 12 (12) CD000551
  • 137 Lazaridis KN, Gores GJ, Lindor KD. Ursodeoxycholic acid ‘mechanisms of action and clinical use in hepatobiliary disorders’. J Hepatol 2001; 35 (01) 134-146
  • 138 Poupon R, Poupon RE. Ursodeoxycholic acid therapy of chronic cholestatic conditions in adults and children. Pharmacol Ther 1995; 66 (01) 1-15
  • 139 Paumgartner G, Beuers U. Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited. Hepatology 2002; 36 (03) 525-531
  • 140 Abdulrab S, Al-Maweri S, Halboub E. Ursodeoxycholic acid as a candidate therapeutic to alleviate and/or prevent COVID-19-associated cytokine storm. Med Hypotheses 2020; 143: 109897
  • 141 Subramanian S, Iles T, Ikramuddin S, Steer CJ. Merit of an ursodeoxycholic acid clinical trial in COVID-19 patients. Vaccines (Basel) 2020; 8 (02) 320
  • 142 Carino A, Moraca F, Fiorillo B. et al. Hijacking SARS-CoV-2/ACE2 receptor interaction by natural and semi-synthetic steroidal agents acting on functional pockets on the receptor binding domain. Front Chem 2020; 8: 572885
  • 143 Rodal Canales FJ, Pérez-Campos Mayoral L, Hernández-Huerta MT. et al. Interaction of Spike protein and lipid membrane of SARS-CoV-2 with Ursodeoxycholic acid, an in-silico analysis. Sci Rep 2021; 11 (01) 22288
  • 144 Fiorillo B, Marchianò S, Moraca F. et al. Discovery of bile acid derivatives as potent ACE2 activators by virtual screening and essential dynamics. J Chem Inf Model 2022; 62 (01) 196-209
  • 145 Thuy PX, Bao TDD, Moon EY. Ursodeoxycholic acid ameliorates cell migration retarded by the SARS-CoV-2 spike protein in BEAS-2B human bronchial epithelial cells. Biomed Pharmacother 2022; 150: 113021
  • 146 Brevini T, Maes M, Webb GJ. et al; UK-PBC Consortium. FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2. Nature 2023; 615 (7950) 134-142
  • 147 John BV, Bastaich D, Webb G. et al. Ursodeoxycholic acid is associated with a reduction in SARS-CoV-2 infection and reduced severity of COVID-19 in patients with cirrhosis. J Intern Med 2023; 293 (05) 636-647
  • 148 Yu D, Song Z-Y, Liu Y. et al. Oral Ursodeoxycholic acid therapy failed to mitigate SARS-CoV-2 omicron variants BA.5.2 infection. Research Square 2023; DOI: 10.21203/RS.3.RS-2717720/V1.
  • 149 The Application of Ursodeoxycholic Acid for the Prevention of SARS-CoV-2 Infection (COVID-19) - Full Text View - ClinicalTrials.gov. Accessed May 23, 2023, at: https://clinicaltrials.gov/ct2/show/NCT05659654
  • 150 UDCA in the Treatment of COVID-19 Infection and Its Clinical Prognosis in Patients With Autoimmune Liver Disease - Full Text View - ClinicalTrials.gov. Accessed May 23, 2023, at: https://clinicaltrials.gov/ct2/show/NCT05812612
  • 151 Effect of Ursodeoxycholic Acid on Preventing COVID-19 Infection in Patients with Organ Transplantation - Full Text View - ClinicalTrials.gov. Accessed May 23, 2023, at: https://clinicaltrials.gov/ct2/show/NCT05685888
  • 152 Schneider L, Schubert L, Winkler F, Munda P, Winkler S, Tobudic S. SARS-CoV-2 vaccine response in patients with autoimmune hepatitis. Clin Gastroenterol Hepatol 2022; 20 (09) 2145-2147.e2