Skip to main content
Top
Published in: Digestive Diseases and Sciences 6/2023

Open Access 03-02-2023 | Hepatitis B | Original Article

Tenofovir Disoproxil Fumarate Reduces the Severity of COVID-19 in Patients with Chronic Hepatitis B

Authors: Beatriz Mateos-Muñoz, María Buti, Inmaculada Fernández Vázquez, Marta Hernández Conde, Vanesa Bernal-Monterde, Fernando Díaz-Fontenla, Rosa María Morillas, Luisa García-Buey, Ester Badía, Mireia Miquel, Alberto Amador-Navarrete, Sergio Rodríguez-Tajes, Lucía Ramos-Merino, Antonio Madejón, Montserrat García-Retortillo, Juan Ignacio Arenas, Joaquín Cabezas, Jesús Manuel González Santiago, Conrado Fernández-Rodríguez, Patricia Cordero, Moisés Diago, Antonio Mancebo, Alberto Pardo, Manuel Rodríguez, Elena Hoyas, Jose Javier Moreno, Juan Turnes, Miguel Ángel Simón, Cristina Marcos-Fosch, Jose Luis Calleja, Rafael Bañares, Sabela Lens, Javier Garcia-Samaniego, Javier Crespo, Manuel Romero-Gomez, Francisco Gea, Enrique Rodríguez de Santiago, Santiago Moreno, Agustin Albillos

Published in: Digestive Diseases and Sciences | Issue 6/2023

Login to get access

Abstract

Background and Aims

HIV-positive patients on tenofovir hydroxyl fumarate (TDF)/emtricitabine have a lower risk of COVID-19 and hospitalization than those given other treatments. Our aim was to analyze the severity of COVID-19 in patients with chronic hepatitis B (CHB) on TDF or entecavir (ETV).

Methods

Spanish hospital databases (n = 28) including information regarding adult CHB patients on TDF or ETV for the period February 1st to November 30th 2020 were searched for COVID-19, defined as a positive SARS-CoV-2 polymerase chain reaction, and for severe COVID-19.

Results

Of 4736 patients, 117 had COVID-19 (2.5%), 67 on TDF and 50 on ETV. Compared to patients on TDF, those on ETV showed (p < 0.05) greater rates of obesity, diabetes, ischemic cardiopathy, and hypertension. COVID-19 incidence was similar in both groups (2.3 vs. 2.6%). Compared to TDF, patients on ETV more often (p < 0.01) had severe COVID-19 (36 vs. 6%), required intensive care unit (ICU) (10% vs. 0) or ventilatory support (20 vs. 3%), were hospitalized for longer (10.8 ± 19 vs. 3.1 ± 7 days) or died (10 vs. 1.5%, p = 0.08). In an IPTW propensity score analysis adjusted for age, sex, obesity, comorbidities, and fibrosis stage, TDF was associated with a sixfold reduction in severe COVID-19 risk (adjusted-IPTW-OR 0.17, 95%CI 0.04–0.67, p = 0.01).

Conclusion

Compared to ETV, TDF seems to play a protective role in CHB patients with SARS-CoV-2 whereby the risk of severe COVID-19 is lowered.
Appendix
Available only for authorised users
Literature
2.
go back to reference European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu, European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370–398. European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu, European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370–398.
3.
go back to reference Arribas JR, Polo R, García JG, Palacios R. Esteban Martínez (GeSIDA). 145. Arribas JR, Polo R, García JG, Palacios R. Esteban Martínez (GeSIDA). 145.
4.
go back to reference del Amo J, Polo R, Moreno S et al. Incidence and severity of COVID-19 in HIV-positive persons receiving antiretroviral therapy. Ann Intern Med. 2020;173:536–541.CrossRefPubMed del Amo J, Polo R, Moreno S et al. Incidence and severity of COVID-19 in HIV-positive persons receiving antiretroviral therapy. Ann Intern Med. 2020;173:536–541.CrossRefPubMed
5.
go back to reference Hoffmann C, Casado JL, Härter G et al. Immune deficiency is a risk factor for severe COVID-19 in people living with HIV. HIV Med. 2021;22:372–378.CrossRefPubMed Hoffmann C, Casado JL, Härter G et al. Immune deficiency is a risk factor for severe COVID-19 in people living with HIV. HIV Med. 2021;22:372–378.CrossRefPubMed
6.
go back to reference Berenguer J, Díez C, Martín-Vicente M et al. Prevalence and factors associated with SARS-CoV-2 seropositivity in the Spanish HIV Research Network Cohort. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2021;27:1678–1684. Berenguer J, Díez C, Martín-Vicente M et al. Prevalence and factors associated with SARS-CoV-2 seropositivity in the Spanish HIV Research Network Cohort. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2021;27:1678–1684.
7.
go back to reference Rial-Crestelo D, Bisbal O, Font R, et al. Incidence and severity of SARS-CoV-2 infection in HIV-infected individuals during the first year of the pandemic. J Acquir Immune Defic Syndr. 2021 Rial-Crestelo D, Bisbal O, Font R, et al. Incidence and severity of SARS-CoV-2 infection in HIV-infected individuals during the first year of the pandemic. J Acquir Immune Defic Syndr. 2021
8.
go back to reference Wu J, Yu J, Shi X et al. Epidemiological and clinical characteristics of 70 cases of coronavirus disease and concomitant hepatitis B virus infection: a multicentre descriptive study. J Viral Hepat. 2021;28:80–88.CrossRefPubMed Wu J, Yu J, Shi X et al. Epidemiological and clinical characteristics of 70 cases of coronavirus disease and concomitant hepatitis B virus infection: a multicentre descriptive study. J Viral Hepat. 2021;28:80–88.CrossRefPubMed
9.
go back to reference Lv X-H, Yang J-L, Deng K. COVID-19 patients with hepatitis B virus infection. Off J Am Coll Gastroenterol. 2021;116:1357–1358.CrossRef Lv X-H, Yang J-L, Deng K. COVID-19 patients with hepatitis B virus infection. Off J Am Coll Gastroenterol. 2021;116:1357–1358.CrossRef
10.
go back to reference Alqahtani SA, Buti M. COVID-19 and hepatitis B infection. Antivir Ther. 2021. Alqahtani SA, Buti M. COVID-19 and hepatitis B infection. Antivir Ther. 2021.
12.
go back to reference Ampuero J, Sánchez Y, García-Lozano MR et al. Impact of liver injury on the severity of COVID-19: a systematic review with meta-analysis. Rev Espanola Enfermedades Dig Organo Of Soc Espanola Patol Dig. 2021;113:125–135. Ampuero J, Sánchez Y, García-Lozano MR et al. Impact of liver injury on the severity of COVID-19: a systematic review with meta-analysis. Rev Espanola Enfermedades Dig Organo Of Soc Espanola Patol Dig. 2021;113:125–135.
13.
go back to reference Guerra Veloz MF, Cordero Ruiz P, Ríos-Villegas MJ et al. Liver manifestations in COVID-19 and the influence of pre-existing liver disease in the course of the infection. Rev Espanola Enfermedades Dig Organo Of Soc Espanola Patol Dig. 2021;113:103–109. Guerra Veloz MF, Cordero Ruiz P, Ríos-Villegas MJ et al. Liver manifestations in COVID-19 and the influence of pre-existing liver disease in the course of the infection. Rev Espanola Enfermedades Dig Organo Of Soc Espanola Patol Dig. 2021;113:103–109.
14.
go back to reference Liu J, Wang T, Cai Q, et al. Longitudinal changes of liver function and hepatitis B reactivation in COVID‐19 patients with pre‐existing chronic HBV infection. Hepatol Res. 2020 Liu J, Wang T, Cai Q, et al. Longitudinal changes of liver function and hepatitis B reactivation in COVID‐19 patients with pre‐existing chronic HBV infection. Hepatol Res. 2020
15.
go back to reference Rodríguez-Tajes S, Miralpeix A, Costa J et al. Low risk of hepatitis B reactivation in patients with severe COVID-19 who receive immunosuppressive therapy. J Viral Hepat. 2021;28:89–94.CrossRefPubMed Rodríguez-Tajes S, Miralpeix A, Costa J et al. Low risk of hepatitis B reactivation in patients with severe COVID-19 who receive immunosuppressive therapy. J Viral Hepat. 2021;28:89–94.CrossRefPubMed
17.
go back to reference Pirracchio R, Resche-Rigon M, Chevret S. Evaluation of the Propensity score methods for estimating marginal odds ratios in case of small sample size. BMC Med Res Methodol. 2012;12:70.CrossRefPubMedPubMedCentral Pirracchio R, Resche-Rigon M, Chevret S. Evaluation of the Propensity score methods for estimating marginal odds ratios in case of small sample size. BMC Med Res Methodol. 2012;12:70.CrossRefPubMedPubMedCentral
18.
go back to reference Birkus G, Hájek M, Kramata P, Votruba I, Holý A, Otová B. Tenofovir diphosphate is a poor substrate and a weak inhibitor of rat DNA polymerases alpha, delta, and epsilon*. Antimicrob Agents Chemother. 2002;46:1610–1613.CrossRefPubMedPubMedCentral Birkus G, Hájek M, Kramata P, Votruba I, Holý A, Otová B. Tenofovir diphosphate is a poor substrate and a weak inhibitor of rat DNA polymerases alpha, delta, and epsilon*. Antimicrob Agents Chemother. 2002;46:1610–1613.CrossRefPubMedPubMedCentral
19.
go back to reference Elfiky AA. Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study. Life Sci. 2020;15:117592.CrossRef Elfiky AA. Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study. Life Sci. 2020;15:117592.CrossRef
21.
go back to reference Jockusch S, Tao C, Li X et al. A library of nucleotide analogues terminate RNA synthesis catalyzed by polymerases of coronaviruses that cause SARS and COVID-19. Antiviral Res. 2020;180:104857.CrossRefPubMedPubMedCentral Jockusch S, Tao C, Li X et al. A library of nucleotide analogues terminate RNA synthesis catalyzed by polymerases of coronaviruses that cause SARS and COVID-19. Antiviral Res. 2020;180:104857.CrossRefPubMedPubMedCentral
22.
go back to reference Xie X, Muruato AE, Zhang X et al. A nanoluciferase SARS-CoV-2 for rapid neutralization testing and screening of anti-infective drugs for COVID-19. Nat Commun. 2020;11:5214.CrossRefPubMedPubMedCentral Xie X, Muruato AE, Zhang X et al. A nanoluciferase SARS-CoV-2 for rapid neutralization testing and screening of anti-infective drugs for COVID-19. Nat Commun. 2020;11:5214.CrossRefPubMedPubMedCentral
23.
go back to reference Melchjorsen J, Risør MW, Søgaard OS et al. Tenofovir selectively regulates production of inflammatory cytokines and shifts the IL-12/IL-10 balance in human primary cells. J Acquir Immune Defic Syndr. 2011;57:265–275.CrossRefPubMed Melchjorsen J, Risør MW, Søgaard OS et al. Tenofovir selectively regulates production of inflammatory cytokines and shifts the IL-12/IL-10 balance in human primary cells. J Acquir Immune Defic Syndr. 2011;57:265–275.CrossRefPubMed
Metadata
Title
Tenofovir Disoproxil Fumarate Reduces the Severity of COVID-19 in Patients with Chronic Hepatitis B
Authors
Beatriz Mateos-Muñoz
María Buti
Inmaculada Fernández Vázquez
Marta Hernández Conde
Vanesa Bernal-Monterde
Fernando Díaz-Fontenla
Rosa María Morillas
Luisa García-Buey
Ester Badía
Mireia Miquel
Alberto Amador-Navarrete
Sergio Rodríguez-Tajes
Lucía Ramos-Merino
Antonio Madejón
Montserrat García-Retortillo
Juan Ignacio Arenas
Joaquín Cabezas
Jesús Manuel González Santiago
Conrado Fernández-Rodríguez
Patricia Cordero
Moisés Diago
Antonio Mancebo
Alberto Pardo
Manuel Rodríguez
Elena Hoyas
Jose Javier Moreno
Juan Turnes
Miguel Ángel Simón
Cristina Marcos-Fosch
Jose Luis Calleja
Rafael Bañares
Sabela Lens
Javier Garcia-Samaniego
Javier Crespo
Manuel Romero-Gomez
Francisco Gea
Enrique Rodríguez de Santiago
Santiago Moreno
Agustin Albillos
Publication date
03-02-2023
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 6/2023
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-022-07817-w

Other articles of this Issue 6/2023

Digestive Diseases and Sciences 6/2023 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.