gastro-jРоссийский журнал гастроэнтерологии, гепатологии, колопроктологииRussian Journal of Gastroenterology, Hepatology, Coloproctology1382-43762658-6673«Gastro» LLC10.22416/1382-4376-2023-33-6-65-80gastro-j-731Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL ARTICLESВлияние новой коронавирусной инфекции на течение и прогноз цирроза печениImpact of Novel Coronavirus Infection on the Course and Prognosis of Cirrhosishttps://orcid.org/0000-0001-6835-4882ИсмаиловаА. Г.IsmailovaA. G.

Исмаилова Альбина Геннадьевна* — ординатор кафедры пропедевтики внутренних болезней лечебного факультета гастроэнтерологии и гепатологии

119435, г. Москва, ул. Погодинская, 1, стр. 1

Albina G. Ismailova — Resident Physician, Department of Internal Disease, Gastroenterology and Hepatology, Faculty of Medicine

19435, Moscow, Pogodinskaya str., 1, build. 1

exalay@mail.ruhttps://orcid.org/0000-0001-7513-1636МасленниковР. В.MaslennikovR. V.

Масленников Роман Вячеславович — кандидат медицинских наук, ассистент кафедры пропедевтики внутренних болезней лечебного факультета гастроэнтерологии и гепатологии

119435, г. Москва, ул. Погодинская, 1

Roman V. Maslennikov — Cand. Sci. (Med.), Teaching Assistant of the Department of Internal Disease, Gastroenterology and Hepatology, Faculty of Medicine

19435, Moscow, Pogodinskaya str., 1, build. 1

https://orcid.org/0000-0001-5939-1032ЖарковаМ. С.ZharkovaM. S.

Жаркова Мария Сергеевна — кандидат медицинских наук, заведующая отделением гепатологии Клиники пропедевтики внутренних болезней, гастроэнтерологии, гепатологии им. В.Х. Василенко

119435, г. Москва, ул. Погодинская, 1, стр. 1

Maria S. Zharkova — Cand. Sci. (Med.), Head of the Department of Hepatology, Clinic of Internal Disease, Gastroenterology and Hepatology named after V.Kh. Vasilenko

19435, Moscow, Pogodinskaya str., 1, build. 1

https://orcid.org/0000-0002-6815-6015ИвашкинВ. Т.IvashkinV. T.

Ивашкин Владимир Трофимович — доктор медицинских наук, профессор, академик РАН, заведующий кафедрой пропедевтики внутренних болезней, гастроэнтерологии и гепатологии

119435, г. Москва, ул. Погодинская, 1, стр. 1

Vladimir T. Ivashkin — Dr. Sci. (Med.), Professor, Full Member of the Russian Academy of Sciences, Head of the Department of Internal Disease, Gastroenterology and Hepatology

19435, Moscow, Pogodinskaya str., 1, build. 1

ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Министерства здравоохранения Российской Федерации (Сеченовский Университет)РоссияI.M. Sechenov First Moscow State Medical University (Sechenov University)Russian Federation2023040120243366580Copyright © Исмаилова А.Г., Масленников Р.В., Жаркова М.С., Ивашкин В.Т., 20242024Исмаилова А.Г., Масленников Р.В., Жаркова М.С., Ивашкин В.Т.Ismailova A.G., Maslennikov R.V., Zharkova M.S., Ivashkin V.T.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.gastro-j.ru/jour/article/view/731

Цель исследования: изучение влияния COVID-19 на течение и прогноз цирроза печени.Материалы и методы. В данное когортное исследование были включены пациенты с циррозом печени, проходившие медицинское обследование в период с сентября 2019 по март 2020 г. Было определено, кто из этих пациентов был инфицирован COVID-19, умер от COVID-19 или осложнений цирроза печени в течение периода наблюдения (с апреля 2020 по сентябрь 2021 г.). Далее в сентябре — декабре 2021 г. было проведено повторное медицинское обследование включенных выживших пациентов.Результаты. Среди 226 включенных пациентов у 57 был выявлен COVID-19, в том числе 19 пациентов умерли от этой болезни. Острая на фоне хронической печеночная недостаточность (ОХПН) развилась у 16 (28,1 %) пациентов с циррозом печени и COVID-19, 13 (81,3 %) из которых умерли. Один из выживших после COVID-19 пациентов в итоге умер от декомпенсации функции печени. Двадцать пациентов, у которых не было COVID-19, умерли от осложнений цирроза печени (ОХПН) в течение периода наблюдения. Уровень смертности у пациентов, инфицированных COVID-19, был выше, чем у не перенесших это заболевание (35,1 % vs. 14,2 %; р = 0,001). COVID-19 был независимым фактором риска смерти у пациентов с циррозом печени. Специфических для поражения печени факторов, предрасполагающих к заражению COVID-19, выявлено не было. Более значительные нарушения функции печени при медицинском обследовании перед пандемией были фактором риска смерти пациентов, переболевших COVID-19. Пациенты, умершие от COVID-19, имели состояние функции печени при медицинском обследовании перед пандемией лучше, чем пациенты, которые умерли от осложнений цирроза печени в течение периода наблюдения. Смертность из-за декомпенсации функции печени, частота декомпенсации печени и кровотечений из варикозно расширенных вен пищевода в течение периода наблюдения существенно не отличались между пациентами, выздоровевшими от COVID-19, и пациентами с циррозом печени, у которые не переносили эту инфекцию. Среди выживших не выявлено значимой разницы в значении основных показателей функции печени между пациентами, перенесшими и не перенесшими COVID-19, за исключением протромбинового индекса, который был выше у пациентов после COVID-19. Заключение. COVID-19 ухудшает прогноз пациентов с циррозом печени, но не оказывает существенного влияния на течение цирроза печени после выздоровления от этой инфекции. 

Аim

Аim: to investigate the impact of COVID-19 on the course and prognosis of cirrhosis.

Materials and methods

Materials and methods. This was a cohort study in patients with cirrhosis. We included patients with cirrhosis who underwent a medical examination at our center between September 2019 and March 2020. We determined which of these patients were infected with COVID-19, died of COVID-19, or died of cirrhosis complications within the follow-up period from April 2020 to September 2021. Thereafter, we conducted a second medical examination of these surviving patients with cirrhosis in September to December 2021.

Results

Results. Among the 226 patients included in the study, 57 had COVID-19, among which 19 patients who died of the disease. Acute-on-chronic liver failure (ACLF) developed in 16 (28.1 %) patients with cirrhosis and COVID-19, 13 (81.3 %) of whom died. One of the COVID-19 survivors eventually died of liver decompensation. Twenty patients who did not have COVID-19 died of complications of cirrhosis (ACLF) during the follow-up period. The mortality rate in patients who were infected with COVID-19 was higher than that in patients who were not infected (35.1 % vs. 14.2 %; p = 0.001). COVID-19 was an independent risk factor for death in patients with cirrhosis. No liver-specific factors predisposing to COVID-19 infection were identified. A more impaired liver function in the pre-pandemic medical examination was a predisposing factor for death in patients who had COVID-19. Patients who died of COVID-19 had better liver function in the pre-pandemic medical examination than patients without COVID-19 who died of complications of cirrhosis during the follow-up period. The liver-related mortality rate and the incidence of liver decompensation or bleeding from esophageal varices during the follow-up period were not significantly different between patients who recovered from COVID-19 and patients with cirrhosis who did not have COVID-19. Among the analyzed survivors, no significant changes were found in the main indicators of liver function after the follow-up period between patients with and without COVID-19, except for the prothrombin index, which was higher in patients after COVID-19.

Conclusion

Conclusion. COVID-19 worsens the prognosis of patients with cirrhosis but does not substantially affect the course of cirrhosis after the recovery from this infection.

COVID-19SARS-CoV-2коронавируспеченьцирроз печенипрогнозCOVID-19SARS-CoV-2CoronavirusLiverCirrhosisPrognosisReferencesSimon T.G., Hagström H., Sharma R., Söderling J., Roelstraete B., Larsson E., et al. Risk of severe COVID-19 and mortality in patients with established chronic liver disease: A nationwide matched cohort study. BMC Gastroenterol. 2021;21(1):439. DOI: 10.1186/s12876-021-02017-8Simon T.G., Hagström H., Sharma R., Söderling J., Roelstraete B., Larsson E., et al. Risk of severe COVID-19 and mortality in patients with established chronic liver disease: A nationwide matched cohort study. BMC Gastroenterol. 2021;21(1):439. DOI: 10.1186/s12876-021-02017-8Elhence A., Vaishnav M., Biswas S., Anand A., Gunjan D., Kedia S., et al. Predictors of in-hospital outcomes in patients with cirrhosis and Coronavirus disease-2019. J Clin Exp Hepatol. 2021;12(3):876–86. DOI: 10.1016/j. jceh.2021.10.014Elhence A., Vaishnav M., Biswas S., Anand A., Gunjan D., Kedia S., et al. Predictors of in-hospital outcomes in patients with cirrhosis and Coronavirus disease-2019. J Clin Exp Hepatol. 2021;12(3):876–86. DOI: 10.1016/j. jceh.2021.10.014Middleton P., Hsu C., Lythgoe M.P. Clinical outcomes in COVID-19 and cirrhosis: A systematic review and meta-analysis of observational studies. BMJ Open Gastroenterol. 2021;8(1):e000739. DOI: 10.1136/bmjgast-2021-000739Middleton P., Hsu C., Lythgoe M.P. Clinical outcomes in COVID-19 and cirrhosis: A systematic review and meta-analysis of observational studies. BMJ Open Gastroenterol. 2021;8(1):e000739. DOI: 10.1136/bmjgast-2021-000739Ge J., Pletcher M.J., Lai J.C.; N3C Consortium. Outcomes of SARS-CoV-2 infection in patients with chronic liver disease and cirrhosis: A National COVID Cohort Collaborative study. Gastroenterology. 2021;161(5):1487–501. DOI: 10.1053/j.gastro.2021.07.010Ge J., Pletcher M.J., Lai J.C.; N3C Consortium. Outcomes of SARS-CoV-2 infection in patients with chronic liver disease and cirrhosis: A National COVID Cohort Collaborative study. Gastroenterology. 2021;161(5):1487–501. DOI: 10.1053/j.gastro.2021.07.010Xiao Y., Wu D., Shi X., Liu S., Hu X., Zhou C., et al. High Child – Pugh and CRUB65 scores predict mortality of decompensated cirrhosis patients with COVID-19: A 23-center, retrospective study. Virulence. 2021;12(1):1199–208. DOI: 10.1080/21505594.2021.1909894Xiao Y., Wu D., Shi X., Liu S., Hu X., Zhou C., et al. High Child – Pugh and CRUB65 scores predict mortality of decompensated cirrhosis patients with COVID-19: A 23-center, retrospective study. Virulence. 2021;12(1):1199–208. DOI: 10.1080/21505594.2021.1909894Bajaj J.S., Garcia-Tsao G., Wong F., Biggins S.W., Kamath P.S., McGeorge S., et al. Cirrhosis is associated with high mortality and readmissions over 90 days regardless of COVID-19: A multicenter cohort. Liver Transpl. 2021;27(9):1343–7. DOI: 10.1002/lt.25981Bajaj J.S., Garcia-Tsao G., Wong F., Biggins S.W., Kamath P.S., McGeorge S., et al. Cirrhosis is associated with high mortality and readmissions over 90 days regardless of COVID-19: A multicenter cohort. Liver Transpl. 2021;27(9):1343–7. DOI: 10.1002/lt.25981Gaspar R., Castelo Branco C., Macedo G. Liver and COVID-19: From care of patients with liver diseases to liver injury. World J Hepatol. 2021;13(10):1367–77. DOI: 10.4254/wjh.v13.i10.1367Gaspar R., Castelo Branco C., Macedo G. Liver and COVID-19: From care of patients with liver diseases to liver injury. World J Hepatol. 2021;13(10):1367–77. DOI: 10.4254/wjh.v13.i10.1367Vairappan B., Wright G., Corrigal D., Ts R. Liver injury in COVID-19: A direct hit or collateral damage? Infect Disord Drug Targets. 2022;22(1):e130921196417. DOI: 10.2 174/1871526521666210913110500Vairappan B., Wright G., Corrigal D., Ts R. Liver injury in COVID-19: A direct hit or collateral damage? Infect Disord Drug Targets. 2022;22(1):e130921196417. DOI: 10.2 174/1871526521666210913110500Su Y.J., Chang C.W., Chen M.J., Lai Y.C. Impact of COVID-19 on liver. World J Clin Cases. 2021;9(27):7998– 8007. DOI: 10.12998/wjcc.v9.i27.7998Su Y.J., Chang C.W., Chen M.J., Lai Y.C. Impact of COVID-19 on liver. World J Clin Cases. 2021;9(27):7998– 8007. DOI: 10.12998/wjcc.v9.i27.7998Mikolasevic I., Bozic D., Pavić T., Ruzic A., Hauser G., Radic M., et al. Liver disease in the era of COVID-19: Is the worst yet to come? World J Gastroenterol. 2021;27(36):6039–52. DOI: 10.3748/wjg.v27.i36.6039Mikolasevic I., Bozic D., Pavić T., Ruzic A., Hauser G., Radic M., et al. Liver disease in the era of COVID-19: Is the worst yet to come? World J Gastroenterol. 2021;27(36):6039–52. DOI: 10.3748/wjg.v27.i36.6039Gracia-Ramos A.E., Jaquez-Quintana J.O., Contreras-Omaña R., Auron M. Liver dysfunction and SARS-CoV-2 infection. World J Gastroenterol. 2021;27(26):3951–70. DOI: 10.3748/wjg.v27.i26.3951Gracia-Ramos A.E., Jaquez-Quintana J.O., Contreras-Omaña R., Auron M. Liver dysfunction and SARS-CoV-2 infection. World J Gastroenterol. 2021;27(26):3951–70. DOI: 10.3748/wjg.v27.i26.3951Del Zompo F., De Siena M., Ianiro G., Gasbarrini A., Pompili M., Ponziani F.R. Prevalence of liver injury and correlation with clinical outcomes in patients with COVID-19: Systematic review with meta-analysis. Eur Rev Med Pharmacol Sci. 2020;24(24):13072–88. DOI: 10.26355/eurrev_202012_24215Del Zompo F., De Siena M., Ianiro G., Gasbarrini A., Pompili M., Ponziani F.R. Prevalence of liver injury and correlation with clinical outcomes in patients with COVID-19: Systematic review with meta-analysis. Eur Rev Med Pharmacol Sci. 2020;24(24):13072–88. DOI: 10.26355/eurrev_202012_24215Limon-De La Rosa N., Cervantes-Alvarez E., Navarro-Alvarez N. Increased hepatic expression of SARS-CoV-2 entry points and proinflammatory cytokines in cirrhosis. Clin Gastroenterol Hepatol. 2022;20(1):239–41.e3. DOI: 10.1016/j.cgh.2021.08.053Limon-De La Rosa N., Cervantes-Alvarez E., Navarro-Alvarez N. Increased hepatic expression of SARS-CoV-2 entry points and proinflammatory cytokines in cirrhosis. Clin Gastroenterol Hepatol. 2022;20(1):239–41.e3. DOI: 10.1016/j.cgh.2021.08.053Seow J.J.W., Pai R., Mishra A., Shepherdson E., Lim T.K.H., Goh B.K.P. Single-cell RNA-seq reveals angiotensin-converting enzyme 2 and transmembrane serine protease 2 expression in TROP2+ liver progenitor cells: Implications in Coronavirus Disease 2019-associated liver dysfunction. Front Med (Lausanne). 2021;8:603374. DOI: 10.3389/fmed.2021.603374Seow J.J.W., Pai R., Mishra A., Shepherdson E., Lim T.K.H., Goh B.K.P. Single-cell RNA-seq reveals angiotensin-converting enzyme 2 and transmembrane serine protease 2 expression in TROP2+ liver progenitor cells: Implications in Coronavirus Disease 2019-associated liver dysfunction. Front Med (Lausanne). 2021;8:603374. DOI: 10.3389/fmed.2021.603374Kim D., Bonham C.A., Konyn P., Cholankeril G., Ahmed A. Mortality trends in chronic liver disease and cirrhosis in the United States, before and during COVID-19 pandemic. Clin Gastroenterol Hepatol. 2021;19(12):2664– 6. DOI: 10.1016/j.cgh.2021.07.009Kim D., Bonham C.A., Konyn P., Cholankeril G., Ahmed A. Mortality trends in chronic liver disease and cirrhosis in the United States, before and during COVID-19 pandemic. Clin Gastroenterol Hepatol. 2021;19(12):2664– 6. DOI: 10.1016/j.cgh.2021.07.009Bajaj J.S., Garcia-Tsao G., Biggins S.W., Kamath P.S., Wong F., McGeorge S., 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(3):531–6. DOI: 10.1136/gutjnl-2020-322118Bajaj J.S., Garcia-Tsao G., Biggins S.W., Kamath P.S., Wong F., McGeorge S., 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(3):531–6. DOI: 10.1136/gutjnl-2020-322118Ioannou G.N., Liang P.S., Locke E., Green P., Berry K., O'Hare A.M., et al. Cirrhosis and severe acute respiratory syndrome coronavirus 2 infection in US veterans: Risk of infection, hospitalization, ventilation, and mortality. Hepatology. 2021;74(1):322–35. DOI: 10.1002/hep.31649Ioannou G.N., Liang P.S., Locke E., Green P., Berry K., O'Hare A.M., et al. Cirrhosis and severe acute respiratory syndrome coronavirus 2 infection in US veterans: Risk of infection, hospitalization, ventilation, and mortality. Hepatology. 2021;74(1):322–35. DOI: 10.1002/hep.31649European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69(2):406–60. DOI: 10.1016/j.jhep.2018.03.024European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69(2):406–60. DOI: 10.1016/j.jhep.2018.03.024Yoshiji H., Nagoshi S., Akahane T., Asaoka Y., Ueno Y., Ogawa K., et al. Evidence-based clinical practice guidelines for Liver Cirrhosis 2020. J Gastroenterol. 2021;56(7):593– 619. DOI: 10.1007/s00535-021-01788-xYoshiji H., Nagoshi S., Akahane T., Asaoka Y., Ueno Y., Ogawa K., et al. Evidence-based clinical practice guidelines for Liver Cirrhosis 2020. J Gastroenterol. 2021;56(7):593– 619. DOI: 10.1007/s00535-021-01788-xZekri-Nechar K., Zamorano-León J.J., Segura-Fragoso A., Alcaide J.R., Reche C., Andrés-Castillo A., et al. Albumin binds COVID-19 spike 1 subunit and predicts in-hospital survival of infected patients-possible alteration by glucose. J Clin Med. 2022;11(3):587. DOI: 10.3390/ jcm11030587Zekri-Nechar K., Zamorano-León J.J., Segura-Fragoso A., Alcaide J.R., Reche C., Andrés-Castillo A., et al. Albumin binds COVID-19 spike 1 subunit and predicts in-hospital survival of infected patients-possible alteration by glucose. J Clin Med. 2022;11(3):587. DOI: 10.3390/ jcm11030587Rabbani G., Ahn S.N. Review: Roles of human serum albumin in prediction, diagnoses and treatment of COVID-19. Int J Biol Macromol. 2021;193 (Pt A):948–55. DOI: 10.1016/j.ijbiomac.2021.10.095Rabbani G., Ahn S.N. Review: Roles of human serum albumin in prediction, diagnoses and treatment of COVID-19. Int J Biol Macromol. 2021;193 (Pt A):948–55. DOI: 10.1016/j.ijbiomac.2021.10.095Hadid T., Kafri Z., Al-Katib A. Coagulation and anticoagulation in COVID-19. Blood Rev. 2021;47:100761. DOI: 10.1016/j.blre.2020.100761Hadid T., Kafri Z., Al-Katib A. Coagulation and anticoagulation in COVID-19. Blood Rev. 2021;47:100761. DOI: 10.1016/j.blre.2020.100761Visco V., Vitale C., Rispoli A., Izzo C., Virtuoso N., Ferruzzi G.J., et al. Post-COVID-19 syndrome: Involvement and interactions between respiratory, cardiovascular and nervous systems. J Clin Med. 2022;11(3):524. DOI: 10.3390/jcm11030524Visco V., Vitale C., Rispoli A., Izzo C., Virtuoso N., Ferruzzi G.J., et al. Post-COVID-19 syndrome: Involvement and interactions between respiratory, cardiovascular and nervous systems. J Clin Med. 2022;11(3):524. DOI: 10.3390/jcm11030524

The authors declare that there are no conflicts of interest present.