Histopathological characteristics in livers of deceased patients with COVID-19

Licet González Fabián; González Teresita Teresita de Jesús González; José Hurtado de Mendoza Amat; Virginia Capó de Paz; Laura López Marín; Marlén Ivón Castellanos Fernández; Enrique Galban García; Enrique Arús Soler; Bienvenido Gra Oramas; Enver Pavel Cayetano Maldonado; Antonio Díaz Machado; Linda Henry; Zobair M. Younossi

doi:10.20517/mtod.2025.87

Metabolism and Target Organ Damage ›› 2025, Vol. 5 ›› Issue (4) :53 DOI: 10.20517/mtod.2025.87

Original Article

Histopathological characteristics in livers of deceased patients with COVID-19

Licet González Fabián ¹
, González Teresita Teresita de Jesús González ²
, José Hurtado de Mendoza Amat ²
, Virginia Capó de Paz ³
, Laura López Marín ⁴
, Marlén Ivón Castellanos Fernández ⁵
, Enrique Galban García ⁵
, Enrique Arús Soler ⁶
, Bienvenido Gra Oramas ⁷^,^†
, Enver Pavel Cayetano Maldonado ⁸
, Antonio Díaz Machado ⁹
, Linda Henry ¹⁰^,¹¹
, Zobair M. Younossi ¹⁰

Author information +

¹Pathological Anatomy Department, Institute of Gastroenterology, Havana 10400, Cuba.

²Pathological Anatomy Department, Dr. Luis Díaz Soto” Clinical Surgical Hospital, Havana 12500, Cuba.

³Pathological Anatomy Department, “Pedro Kourí” Institute of Tropical Medicine, Havana 11300, Cuba.

⁴Pathological Anatomy Department, Abelardo Buch López Nephrology Institute, Havana 10400, Cuba.

⁵Research Department, Institute of Gastroenterology, Havana 10400, Cuba.

⁶Hepatology Department, Hermanos Ameijeiras Hospital, Havana 10200, Cuba.

⁷Pathological Anatomy Department, Institute of Gastroenterology, Havana 10400, Cuba. †Deceased

⁸Education Department, Institute of Gastroenterology, Havana 10400, Cuba.

⁹Research Department, Hermanos Ameijeiras Hospital, Havana 10200, Cuba.

¹⁰The Global NASH/MASH Council, Washington DC 20037, USA.

¹¹The Center for Outcomes Research in Liver Disease, Washington DC 20037, USA.

^†Deceased.

Correspondence to: Dr. Licet González Fabian, Pathological Anatomy Department, Institute of Gastroenterology, Havana 10400, Cuba. E-mail: licetgm1972@gmail.com; Dr. Marlén Ivón Castellanos Fernández, Research Department, Institute of Gastroenterology, Havana 10400, Cuba. mcastellfdez@gmail.com

Show less

History +

PDF

Abstract

Aim: The research aims to describe histopathological characteristics in the livers of deceased patients with COVID-19 and to identify possible associations with clinical and epidemiological variables.

Methods: An observational, descriptive, cross-sectional study was conducted with 559 deceased individuals over 19 years of age who underwent minimally invasive autopsies in various Cuban hospitals between October 2021 and December 2022. Epidemiological and liver histopathological data were analyzed. A logistic regression model was used to evaluate the variables that influence the likelihood of hepatocellular necrosis.

Results: The deceased were predominantly male (n = 323, 58.0%), with a mean age of 69.4 ± 15.6 years. An acute necroinflammatory pattern was predominant, with hepatocellular necrosis observed in 486 cases (87.0%), particularly confluent necrosis in 285 cases (51.0%). Necrosis was associated with multimorbidity odds ratio (OR): 1,986 (1,055-3,737), microvacuolar steatosis (> 5%) OR = 3,348 (1,188-9,439) and steatotic liver disease OR = 8,625 (3,093-24,050). Multivariate analysis confirmed steatotic liver disease adjusted OR = 4.657; (95% confidence interval [CI]: 1.872-14.985) and cirrhosis adjusted OR = 8.294; (95% CI: 3.18-18.762) as significant predictors.

Conclusion: Hepatocellular necrosis, particularly confluent necrosis, was the predominant histopathological lesion in COVID-19 deaths in Cuba and was associated with steatotic liver disease and cirrhosis. These findings highlight the importance of monitoring liver function in patients with pre-existing liver conditions during and after SARS-CoV-2 infection.

Keywords

COVID-19 / liver damage / SARS-CoV-2

Cite this article

Download citation ▾

Licet González Fabián, González Teresita Teresita de Jesús González, José Hurtado de Mendoza Amat, Virginia Capó de Paz, Laura López Marín, Marlén Ivón Castellanos Fernández, Enrique Galban García, Enrique Arús Soler, Bienvenido Gra Oramas, Enver Pavel Cayetano Maldonado, Antonio Díaz Machado, Linda Henry, Zobair M. Younossi. Histopathological characteristics in livers of deceased patients with COVID-19. Metabolism and Target Organ Damage, 2025, 5(4): 53 DOI:10.20517/mtod.2025.87

登录浏览全文

4963

注册一个新账户忘记密码

References

Publishing order | Descend order by publishing year | Descend order by cited within

[1]	Rothan HA.The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak.J Autoimmun2020;109:102433 PMCID:PMC7127067

[2]	Righi FA,Graham RP.A case-control autopsy series of liver pathology associated with novel coronavirus disease (COVID-19).Ann Diagn Pathol2024;68:152240

[3]

Sarin SK,Lau GK.APASL COVID Task ForceAPASL COVID Liver Injury Spectrum Study (APCOLIS Study-NCT 04345640)Pre-existing liver disease is associated with poor outcome in patients with SARS CoV2 infection; The APCOLIS Study (APASL COVID-19 Liver Injury Spectrum Study).Hepatol Int2020;14:690-700 PMCID:PMC7334898

[4]	Sonzogni A,Seghezzi M,Gianatti A.Liver histopathology in severe COVID-19 respiratory failure is suggestive of vascular alterations.Liver Int2020;40:2110-6

[5]	Chornenkyy Y,Bruca M,Dittmann D.Liver pathology and SARS-CoV-2 detection in formalin-fixed tissue of patients with COVID-19.Am J Clin Pathol2021;155:802-14

[6]	Farrokhpour M,Moradi N.Infliximab and intravenous gammaglobulin in hospitalized severe COVID-19 Patients in intensive care unit.Arch Iran Med2021;24:139-43

[7]	Sekhawat V,Mahadeva U.COVID-19 autopsies: conclusions from international studies.Diagn Histopathol2021;27:103-7 PMCID:PMC7719010

[8]	Ministerio de Salud Pública de Cuba. Anuario Estadístico de Salud. Available from: https://temas.sld.cu/estadisticassalud/publicaciones-2/anuario-estadistico-de-salud/ [accessed 27 October 2025]

[9]	Mejías Sánchez Y, Morales Suárez I, Arteaga García A, Alfonso Sánchez I. Estructuración del Protocolo Cubano de Actuación para la Atención de Casos COVID-19. Rev Cub Salud Publica. 2021;47(3). Available from: https://revsaludpublica.sld.cu/index.php/spu/article/view/2922 [accessed 27 October 2025]

[10]	Bruguera M. El examen metódico de la biopsia hepática. In: Bosch J, Rodés J, editors. Enfermedades del hígado. 3rd ed. Barcelona: Elsevier; 2006. p. 1-15. Available from: https://www.elsevier.es/libros/enfermedades-del-higado/9788445815770

[11]	Skou ST,Fortin M.Multimorbidity.Nat Rev Dis Primers2022;8:48 PMCID:PMC7613517

[12]	Barreto IDJ, Múnera Contreras MN, Suárez Causado A. Relación entre el factor de crecimiento hepático y el estadio de la cirrosis.Rev Colomb Gastroenterol2017;32:24. (in Spanish)

[13]	Bursac Z,Williams DK.Purposeful selection of variables in logistic regression.Source Code Biol Med2008;3:17 PMCID:PMC2633005

[14]	Barnes GD.Predicting the quality of warfarin therapy: reframing the question.Thromb Haemost2019;119:509-11

[15]	Heinze G,Dunkler D.Variable selection - a review and recommendations for the practicing statistician.Biom J2018;60:431-49 PMCID:PMC5969114

[16]	Yoneda M,Honda Y.Combination of tofogliflozin and pioglitazone for NAFLD: Extension to the ToPiND randomized controlled trial.Hepatol Commun2022;6:2273-85 PMCID:PMC9426404

[17]	Oyelade T,Canciani G.Prognosis of COVID-19 in patients with liver and kidney diseases: an early systematic review and meta-analysis.Trop Med Infect Dis2020;5:80

[18]	Nardo AD,Bakail M,Lax SF.Pathophysiological mechanisms of liver injury in COVID-19.Liver Int2021;41:20-32 PMCID:PMC7753756

[19]	Xu Z,Wang Y.Pathological findings of COVID-19 associated with acute respiratory distress syndrome.Lancet Respir Med2020;8:420-2

[20]	Liu Q,Qu GQ.Gross examination report of a COVID-19 death autopsy.J Forensic Med2020;36:21-3

[21]	Marjot T,Barritt AS.COVID-19 and liver disease: mechanistic and clinical perspectives.Nat Rev Gastroenterol Hepatol2021;18:348-64 PMCID:PMC7945972

[22]	Singh S.Clinical characteristics and outcomes of coronavirus disease 2019 among patients with preexisting liver disease in the United States: a multicenter research network study.Gastroenterology2020;159:768-771.e3 PMCID:PMC7196546

[23]	Moreira JLS,Vieira JG,Gonçalves Júnior J.Liver histopathological changes and COVID-19: what does literature have to tell us?.Dig Liver Dis2022;54:296-8 PMCID:PMC8752316

[24]	Ji D,Xu J.Non-alcoholic fatty liver diseases in patients with COVID-19: A retrospective study.J Hepatol2020;73:451-3 PMCID:PMC7141624

[25]	Abenavoli L,Sacco MA.Liver damage and impaired coagulation in COVID-19 patients: a case series.Diseases2023;11:141 PMCID:PMC10594514

[26]	Mao R,Shen J.Liver injury in COVID-19: mechanisms and potential therapeutic targets.Lancet Gastroenterol Hepatol2020;5:683-690

[27]	Wang H,Liu J,Zhao Q.The liver injury and gastrointestinal symptoms in patients with Coronavirus Disease 19: A systematic review and meta-analysis.Clin Res Hepatol Gastroenterol2020;44:653-61 PMCID:PMC7214284

[28]	Tazarghi A,Taziki Balajelini MH,Hosseini SM.Liver injury in COVID-19: an insight into pathobiology and roles of risk factors.Virol J2024;21:65. PMCID:PMC10943793

[29]	Cai Y,Song YQ.Liver injury in COVID-19: detection, pathogenesis, and treatment.World J Gastroenterol2021;27:3022-36 PMCID:PMC8192279

[30]	Shi Y,Wu L,Liao Z.COVID-19 associated liver injury: An updated review on the mechanisms and management of risk groups.Liver Res2023;7:207-15 PMCID:PMC11792068