The role of viral hepatitis B and C in the development of adverse outcomes in patients after tuberculosis

Despite the study of the epidemiology of tuberculosis and its co-infection over the past decades, a number of questions remain, including those related to the impact of co-infection on survival depending on the chosen tuberculosis treatment regimen, the likelihood of adverse outcomes in the form of gastrointestinal bleeding and cirrhosis of the liver and their relationship with the therapy of the underlying disease. The purpose of the study: to evaluate the survival of patients with tuberculosis who have co-infection (viral hepatitis B and C) and receive multicomponent chemotherapy. Materials and Methods: The study included all patients who received treatment for active tuberculosis and had viral hepatitis B and/or C from 01/01/2004 to 12/31/2020. A total of 1687 patients were included. Twenty-two patients were lost to follow-up, and attempts to ascertain their clinical status were unsuccessful. Vital status was assessed in all patients. The mean duration of follow-up was 10.5±3.0 years. Median follow-up was 11.3 years (95% confidence interval (CI) 8.2-14.3). The average age of the cohort was 53.3±7.7 years. The study assessed survival and all-cause mortality annually. Results: The frequency of chronic hepatitis B in the group of patients with active tuberculosis was 3.8%, hepatitis C - 14.8%, hepatitis B and C - 0.5% of cases. Such an incidence of viral hepatitis is associated with a high frequency of illicit drug users (62.4%). It should be noted that the frequency of hepatitis treatment was low and amounted to 8.7%. When assessing the contribution of hepatitis B and C to the mortality of patients with active tuberculosis, it was found that hepatitis is not a predictor of death in patients. At the same time, patients who did not receive hepatitis therapy had a higher risk of death (unadjusted odds ratio (OR) - 1.28, 95% CI 1.04-1.65). The adjusted OR for hepatitis B was - 1.87 95% CI 0.67-1.52, C - 1.24 95% CI 0.90-2.18, B and C - 1.72 95% CI 0.99-2.02. Conclusion: The presence of chronic viral hepatitis B and/or C in patients with active tuberculosis did not affect mortality from all causes and regardless of the type of virus during a long period of observation. Patients who did not receive treatment for viral hepatitis and who had a history of tuberculosis had a higher risk of death from all causes (OR 1.28, 95% CI 1.04-1.65).

tuberculosis, viral hepatitis, survival, predictors of death from all causes, co-infections

1. GBD Tuberculosis Collaborators. The global burden of tuberculosis: results from the Global Burden of Disease Study 2015. Lancet Infect Dis. 2018 Mar;18(3):261-284. doi: 10.1016/S1473-3099(17)30703-X.

2. Feleke B.E., Feleke T. E., Adane W. G., Girma A. Impacts of hepatitis B and hepatitis C co-infection with tuberculosis, a prospective cohort study. Virol J. 2020 Jul 23;17(1):113. doi: 10.1186/s12985-020-01385-z.

3. Iglecias L.M., Puga M. A., Pompilio M. A., et al. Epidemiological study of hepatitis B virus among prisoners with active tuberculosis in Central Brazil.Int J Tuberc Lung Dis. 2016;20(11):1509-15.

4. Franco E., Bagnato B., Marino M. G., Meleleo C., Serino L., Zaratti L. Hepatitis B: Epidemiology and prevention in developing countries. World J Hepatol. 2012;4(3):74.

5. Mo P., Zhu Q., Teter C., Yang R., Deng L., Yan Y., et al. Prevalence, druginduced hepatotoxicity, and mortality among patients multi-infected with HIV, tuberculosis, and hepatitis virus.Int J Infect Dis. 2014;28:95-100.

6. Farhoudi B., SeyedAlinaghi S., Mohraz M., Hosseini M., Farnia M. Tuberculosis, hepatitis C and hepatitis B co-infections in patients with HIV in the great Tehran prison, Iran. Asian Pac J Trop Dis. 2016;6(1):82-3.

7. Morbidity of the population with socially significant diseases. Rosstat, 11/30/2021. Last update date: 02/10/2022; access via the link: https://rosstat.gov.ru/storage/mediabank/zdr2-2.xls.@@ Заболеваемость населения социально-значимыми болезнями. Росстат, 30.11.2021. Дата последнего обновления: 10.02.2022; доступ по ссылке: https://rosstat.gov.ru/storage/mediabank/zdr2-2.xls.

8. Nazarov V. Yu., Nechaev V. V., Ivanov A. K., Pozhidaeva L. N., Solomay T. V., Sakra A. Viral hepatitis as co-infection. Of the past to the present and future. Journal Infectology. 2013;5(2):90-95. (In Russ.) doi: 10.22625/2072-6732-2013-5-2-90-95.@@ Назаров В. Ю., Нечаев В. В., Иванов А. К., Пожидаева Л. Н., Соломай Т. В., Сакра А. Вирусные гепатиты и туберкулез как сочетанные инфекции. От прошлого к настоящему и будущему. Журнал инфектологии. 2013;5(2):90-95. doi: 10.22625/2072-6732-2013-5-2-90-95.

9. Chen L., Bao D., Gu L., Gu Y., Zhou L., Gao Z., et al. Co-infection with hepatitis B virus among tuberculosis patients is associated with poor outcomes during anti-tuberculosis treatment. BMC Infect Dis. 2018;18(1):295.

10. Pedrosa M., Nogales S., Vergara M., et al. Reactivation of peritoneal and pleural tuberculosis during hepatitis C treatment with direct-acting antivirals. Gastroenterol Hepatol. 2019;42(3):174-5.

11. Ladep N.G., Agbaji O. O., Agaba P. A., et al. Hepatitis B Co-Infection is Associated with Poorer Survival of HIV-Infected Patients on Highly Active Antiretroviral Therapy in West Africa. J AIDS Clin Res. 2013;2013(Suppl 3):1-7.

12. Kim W.S., Lee S. S., Lee C. M., et al. Hepatitis C and not hepatitis B virus is a risk factor for anti-tuberculosis drug induced liver injury. BMC Infect Dis. 2016;16:50.

13. Clinical guidelines “Chronic viral hepatitis C”, coding according to the International Statistical Classification of Diseases and Related Health Problems: B18.2; year of approval (revision frequency): 2021; age category: adults; end year: 2023; ID:516; available at: https://cr.minzdrav.gov.ru/schema/516_2; last update date: 24.02.2022@@ Клинические рекомендации «Хронический вирусный гепатит С», кодирование по Международной статистической классификации болезней и проблем, связанных со здоровьем: В18.2; год утверждения (частота пересмотра):2021; возрастная категория: взрослые; год окончания действия: 2023; ID:516; доступно по ссылке: https://cr.minzdrav.gov.ru/schema/516_2. дата последнего обновления: 24.02.2022.

14. Clinical guidelines: “Tuberculosis in adults”; coding according to the International Statistical Classification of Diseases and Related Health Problems: A15-A19; year of approval (revision frequency): 2020; age category: adults; end year: 2022; ID: 16; available at: https://cr.minzdrav.gov.ru/schema/16_1; last update date: 24.02.2022.@@ Клинические рекомендации: «Туберкулез у взрослых»; кодирование по Международной статистической классификации болезней и проблем, связанных со здоровьем: A15-A19; год утверждения (частота пересмотра): 2020; возрастная категория: взрослые; год окончания действия:2022; ID: 16; доступно по ссылке: https://cr.minzdrav.gov.ru/schema/16_1. дата последнего обновления: 24.02.2022).

15. Kempker R.R., Alghamdi W. A., Al-Shaer M.H., Burch G., Peloquin C. A. A pharmacology perspective on simultaneous tuberculosis and hepatitis C treatment. Antimicrob Agents Chemother. 2019;63: e01215-19. doi: 10.1128/AAC.01215-19.

16. Reis N.R., Lopes C. L., Teles S. A., et al. Hepatitis C virus infection in patients with tuberculosis in Central Brazil.Int J Tuber Lung Dis. 2011;15:1397-1402. doi: 10.5588/ijtld.10.0636.

17. Asratyan A. A., Solovyev D. V., Rusakova E. V. Tuberculosis and parenteral viral hepatitides: incidence of mixed forms. Tuberculosis and Lung Diseases. 2014;(11):54-57. (In Russ.) doi: 10.21292/2075-1230-2014-0-11-54-57.@@ Асратян А. А., Соловьев Д. В., Русакова Е. В. Туберкулез в сочетании с парентеральными вирусными гепатитами: заболеваемость сочетанными формами. Туберкулез и болезни легких. 2014;(11):54-57. doi: 10.21292/2075-1230-2014-0-11-54-57.

18. Nechaev V. V., Ivanov A. K., Sacra A. A., Romanova E. S., Lyalina L. V., Pozhidaeva L. N. Chronic viral hepatitis, tuberculosis, and HIV as comorbidity: from theory to practice. Journal Infectology. 2017;9(4):126-132. (In Russ.) doi: 10.22625/2072-6732-2017-9-4-126-132.@@ Нечаев В. В., Иванов А. К., Сакра А. А., Романова Е. С., Лялина Л. В., Пожидаева Л. Н. Хронические вирусные гепатиты, туберкулез и ВИЧ-инфекция как сочетанные заболевания: от теории к практике. Журнал инфектологии. 2017;9(4):126-132. doi: 10.22625/2072-6732-2017-9-4-126-132.