Prevalence and molecular genetic characteristics of parenteral hepatitis B, C and D viruses in HIV positive persons in the Novosibirsk region

Cover Image

Cite item

Full Text

Abstract

Introduction. Parenteral viral hepatitis (B, C, D) and HIV share modes of transmission and risk groups, in which the probability of infection with two or more of these viruses simultaneously is increased. Mutual worsening of the course of viral infections is important issue that occurs when HIV positive patients are coinfected with parenteral viral hepatitis.

The aim of the study was to determine the prevalence of HCV, HBV and HDV in HIV positive patients in the Novosibirsk region and to give molecular genetic characteristics of their isolates.

Materials and methods. Total 185 blood samples were tested for the presence of total antibodies to HCV, HCV RNA, HBV DNA and HDV RNA. The identified isolates were genotyped by amplification of the NS5B gene fragment for HCV, the polymerase gene for HBV and whole genome for HDV.

Results. The total antibodies to HCV were detected in 51.9% (95% CI: 44.7–58.9), HCV RNA was detected in 32.9% (95% CI: 26.6–39.5) of 185 studied samples. The distribution of HCV RNA positive cases completely repeated the distribution of HCV serological markers in different sex and age groups. The number of HCV infected among HIV positive patients increases with age. HCV subgenotypes distribution was as follows: 1b (52.5%), 3а (34.5%), 1а (11.5%), 2а (1.5%). 84.3% of detected HCV 1b isolates had C316N mutation associated with resistance to sofosbuvir and dasabuvir. The prevalence of HBV DNA in the studied samples was 15.2% (95% CI: 10.7–21.0). M204I mutation associated with resistance to lamivudine and telbivudine was identified in one HBV isolate. Two HDV isolates that belonged to genotype 1 were detected in HIV/HBV coinfected patients.

Conclusion. The data obtained confirm the higher prevalence of infection with parenteral viral hepatitis among people living with HIV in the Novosibirsk region compared to the general population of that region. The genetic diversity of these viruses among HIV infected individuals is similar to that observed in the general population.

About the authors

Mikhail Yu. Kartashov

State Scientific Center of Virology and Biotechnology “Vector” of the Federal Service for Surveillance of Consumer Rights Protection and Human Welfare (Rospotrebnadzor); Novosibirsk National Research State University

Author for correspondence.
Email: mikkartash@yandex.ru
ORCID iD: 0000-0002-7857-6822

PhD, MD (Biology), Senior Researcher, Department of Flavivirus Infections

Russian Federation, 630559, Novosibirsk Region, Koltsovo; 630090, Novosibirsk

Kirill A. Svirin

State Scientific Center of Virology and Biotechnology “Vector” of the Federal Service for Surveillance of Consumer Rights Protection and Human Welfare (Rospotrebnadzor)

Email: svirin_ka@vector.nsc.ru
ORCID iD: 0000-0001-9083-1649

Junior Researcher, Department of Flavivirus Infections

Russian Federation, 630559, Novosibirsk Region, Koltsovo

Ekaterina I. Krivosheina

State Scientific Center of Virology and Biotechnology “Vector” of the Federal Service for Surveillance of Consumer Rights Protection and Human Welfare (Rospotrebnadzor)

Email: katr962@mail.ru
ORCID iD: 0000-0001-5181-0415

Junior Researcher, Department of Flavivirus Infections

Russian Federation, 630559, Novosibirsk Region, Koltsovo

Elena V. Chub

State Scientific Center of Virology and Biotechnology “Vector” of the Federal Service for Surveillance of Consumer Rights Protection and Human Welfare (Rospotrebnadzor)

Email: chub_ev@vector.nsc.ru
ORCID iD: 0000-0003-1521-897X

PhD, MD (Biology), Biology, head of department

Russian Federation, 630559, Novosibirsk Region, Koltsovo

Vladimir A. Ternovoi

State Scientific Center of Virology and Biotechnology “Vector” of the Federal Service for Surveillance of Consumer Rights Protection and Human Welfare (Rospotrebnadzor)

Email: tern@vector.nsc.ru
ORCID iD: 0000-0003-1275-171X

PhD, MD (Biology), head of the laboratory Department of Flavivirus Infections

Russian Federation, 630559, Novosibirsk Region, Koltsovo

Galina V. Kochneva

State Scientific Center of Virology and Biotechnology “Vector” of the Federal Service for Surveillance of Consumer Rights Protection and Human Welfare (Rospotrebnadzor)

Email: kochneva@vector.nsc.ru
ORCID iD: 0000-0002-2420-0483

Doctor of Biology, head of the laboratory Department of Flavivirus Infections

Russian Federation, 630559, Novosibirsk Region, Koltsovo

References

  1. Gonzalez V.D., Falconer K., Blom K.G., Reichard O., Mørn B., Laursen A.L., et al. High levels of chronic immune activation in the T-cell compartments of patients coinfected with hepatitis C virus and human immunodeficiency virus type 1 and on highly active antiretroviral therapy are reverted by alpha interferon and ribavirin treatment. J. Virol. 2009; 83(21): 11407–11. https://doi.org/10.1128/JVI.01211-09
  2. Kovacs A., Karim R., Mack W.J., Xu J., Chen Z., Operskalski E., et al. Activation of CD8 T cells predicts progression of HIV infection in women coinfected with hepatitis C virus. J. Infect. Dis. 2010; 201(6): 823–34. https://doi.org/10.1086/650997
  3. Rauch A., James I., Pfafferott K., Nolan D., Klenerman P., Cheng W., et al. Divergent adaptation of hepatitis C virus genotypes 1 and 3 to human leukocyte antigen-restricted immune pressure. Hepatology. 2009; 50(4): 1017–29. https://doi.org/10.1002/hep.23101
  4. Tengan F.M., Ibrahim K.Y., Dantas B.P., Manchiero C., Magri M.C, Bernando W.M. Seroprevalence of hepatitis C virus among people living with HIV/AIDS in Latin America and the Caribbean: a systematic review. BMC Infect. Dis. 2016; 16(1): 663. https://doi.org/10.1186/s12879-016-1988-y
  5. Zuckerman A.D., Douglas A., Whelchel K., Choi L., DeClercq J., Chastain C.A., et al. Pharmacologic management of HCV treatment in patients with HCV monoinfection vs. HIV/HCV coinfection: Does coinfection really matter? PLoS One. 2019; 14(11): e0225434. https://doi.org/10.1371/journal.pone.0225434
  6. Cheng Z., Lin P., Cheng N. HBV/HIV coinfection: impact on the development and clinical treatment of liver diseases. Front. Med. (Lausanne). 2021; 8: 713981. https://doi.org/10.3389/fmed.2021.713981
  7. Babu C.K., Suwansrinon K., Bren G.D., Badley A.D., Rizza S.A. HIV induces TRAIL sensitivity in hepatocytes. PLoS One. 2009; 4(2): e4623. https://doi.org/10.1371/journal.pone.0004623
  8. Herbeuval J.P., Boasso A., Grivel J.C., Hardy A.W., Anderson S.A., Dolan M.J., et al. TNF-related apoptosis-inducing ligand (TRAIL) in HIV-1-infected patients and its in vitro production by antigen-presenting cells. Blood. 2005; 105(6): 2458–64. https://doi.org/10.1182/blood-2004-08-3058
  9. Yu Y., Gong R., Mu Y., Chen Y., Zhu C., Sun Z., et al. Hepatitis B virus induces a novel inflammation network involving three inflammatory factors, IL-29, IL-8, and cyclooxygenase-2. J. Immunol. 2011; 187(9): 4844–60. https://doi.org/10.4049/jimmunol.1100998
  10. Lara-Pezzi E., Gómez-Gaviro M.V., Gálvez B.G., Mira E., Iñiguez M.A., Fresno M., et al. The hepatitis B virus X protein promotes tumor cell invasion by inducing membrane-type matrix metalloproteinase-1 and cyclooxygenase2 expression. J. Clin. Investig. 2002; 110(12): 1831–8. https://doi.org/10.1172/JCI15887
  11. Mohammed N.A., Abd El-Aleem S.A., El-Hafiz H.A., McMahon R.F. Distribution of constitutive (COX-1) and inducible (COX-2) cyclooxygenase in postviral human liver cirrhosis: a possible role for COX-2 in the pathogenesis of liver cirrhosis. J. Clin. Pathol. 2004; 57(4): 350–4. https://doi.org/10.1136/jcp.2003.012120
  12. Singh K.P., Crane M., Audsley J., Avihingsanon A., Sasadeusz J., Lewin S.R. HIV-hepatitis B virus coinfection: epidemiology, pathogenesis, and treatment. AIDS. 2017; 31(15): 2035–52. https://doi.org/10.1097/QAD.0000000000001574
  13. Brenchley J.M., Price D.A., Schacker T.W., Asher T.E., Silvestri G., Rao S., et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat. Med. 2006; 12(12): 1365–71. https://doi.org/10.1038/nm1511
  14. Qadir M.I. Hepatitis in AIDS patients. Rev. Med. Virol. 2018; 28(1). https://doi.org/10.1002/rmv.1956
  15. Sulkowski M.S. Viral hepatitis and HIV coinfection. J. Hepatol. 2008; 48(2): 353–67. https://doi.org/10.1016/j.jhep.2007.11.009
  16. Kumar S., Stecher G., Li M., Knyaz C., Tamura K. MEGA X: Molecular Evolutionary Genetics Analysis across computing platforms. Mol. Biol. Evol. 2018; 35(6): 1547–9. https://doi.org/10.1093/molbev/msy096
  17. Titarenko R.V. Features of the drug situation and the problems of drug abuse prevention among Russian teenagers. Gumanitarnye, sotsial’no-ekonomicheskie i obshchestvennye nauki. 2015; (11-1): 191–4. (in Russian)
  18. Soboleva N.V., Karlsen A.A., Kozhanova T.V., Kichatova V.S., Klushkina V.V., Isaeva O.V., et al. The prevalence of the hepatitis C virus among the conditionally healthy population of the Russian Federation. Zhurnal infektologii. 2017; 9(2): 56–64. https://doi.org/10.22625/2072-6732-2017-9-2-56-64 (in Russian)
  19. Guntipalli P., Pakala R., Kumari Gara S., Ahmed F., Bhatnagar A., Endaya Coronel M.K., et al. Worldwide prevalence, genotype distribution and management of hepatitis C. Acta Gastroenterol. Belg. 2021; 84(4): 637–56. https://doi.org/10.51821/84.4.015.
  20. Olinger C.M., Lazouskaya N.V., Eremin V.F., Muller C.P. Multiple genotypes and subtypes of hepatitis B and C viruses in Belarus: similarities with Russia and western European influences. Clin. Microbiol. Infect. 2008; 14(6): 575–81. https://doi.org/10.1111/j.1469-0691.2008.01988.x
  21. Isakov V., Tsyrkunov V., Nikityuk D. Is elimination of hepatitis C virus realistic by 2030: Eastern Europe. Liver Int. 2021; 41(Suppl. 1): 50–5. https://doi.org/10.1111/liv.14836
  22. Rhodes T., Platt L., Maximova S., Koshkina E., Latishevskaya N., Hickman M., et al. Prevalence of HIV, hepatitis C and syphilis among injecting drug users in Russia: a multi-city study. Addiction. 2006; 101(2): 252–66. https://doi.org/10.1111/j.1360-0443.2006.01317.x
  23. Tsui J.I., Ko S.C., Krupitsky E., Lioznov D., Chaisson C.E., Gnatienko N., et al. Insights on the Russian HCV care cascade: minimal HCV treatment for HIV/HCV co-infected PWID in St. Petersburg. Hepatol. Med. Policy. 2016; 1: 13. https://doi.org/10.1186/s41124-016-0020-x
  24. Rhodes T., Platt L., Judd A., Mikhailova L.A., Sarang A., Wallis N., et al. Hepatitis C virus infection, HIV co-infection, and associated risk among injecting drug users in Togliatti, Russia. Int. J. STD AIDS. 2005; 16(11): 749–54. https://doi.org/10.1258/095646205774763180
  25. Bobkova M.R., Samokhvalov E.I., Buravtsova E.V., Detkova N.V., Kravchenko A.V., Salamov G.G., et al. Hepatitis C among HIV-infected intravenous drug users in Russia. Mir virusnykh gepatitov. 2002; (6): 6–9. (in Russian)
  26. Aceijas C., Rhodes T. Global estimates of prevalence of HCV infection among injecting drug users. Int. J. Drug Policy. 2007; 18(5): 352–8. https://doi.org/10.1016/j.drugpo.2007.04.004
  27. Munir S., Saleem S., Idrees M., Tariq A., Butt S., Rauff B., et al. Hepatitis C treatment: current and future perspectives. Virol. J. 2010; 7: 296. https://doi.org/10.1186/1743-422X-7-296
  28. Zein N.N. Clinical significance of hepatitis C virus genotypes. Clin. Microbiol. Rev. 2000; 13(2): 223–35. https://doi.org/10.1128/CMR.13.2.223
  29. Probst A., Dang T., Bochud M., Egger M., Negro F., Bochud P.Y. Role of hepatitis C virus genotype 3 in liver fibrosis progression--a systematic review and meta-analysis. J. Viral. Hepat. 2011; 18(11): 745–59. https://doi.org/10.1111/j.1365-2893.2011.01481.x
  30. Ramalho F. Hepatitis C virus infection and liver steatosis. Antiviral Res. 2003; 60(2): 125–7. https://doi.org/10.1016/j.antiviral.2003.08.007
  31. Esteban J.I., Sauleda S., Quer J. The changing epidemiology of hepatitis C virus infection in Europe. J. Hepatol. 2008; 48(1): 148–62. https://doi.org/10.1016/j.jhep.2007.07.033
  32. Shustov A.V., Kochneva G.V., Sivolobova G.F., Grazhdantseva A.A., Gavrilova I.V., Akinfeeva L.A. The occurrence of markers, the distribution of genotypes and risk factors for viral hepatitis C among some groups of the population of the Novosibirsk region. Zhurnal mikrobiologii, epidemiologii i immunobiologii. 2004; 71(5): 20–5. (in Russian)
  33. Schinazi R., Halfon P., Marcellin P., Asselah T. HCV direct-acting antiviral agents: the best interferon-free combinations. Liver Int. 2014; 34(Suppl. 1): 69–78. https://doi.org/10.1111/liv.12423
  34. D’Ambrosio R., Degasperi E., Colombo M., Aghemo A. Direct-acting antivirals: the endgame for hepatitis C? Curr. Opin. Virol. 2017; 24: 31–7. https://doi.org/10.1016/j.coviro.2017.03.017
  35. Feld J.J. Direct-acting antivirals for Hepatitis C Virus (HCV): The progress continues. Curr. Drug Targets. 2017; 18(7): 851–62. https://doi.org/10.2174/1389450116666150825111314
  36. Zhang Y., Cao Y., Zhang R., Zhang X., Lu H., Wu C., et al. Pre-existing HCV variants resistant to DAAs and their sensitivity to PegIFN/RBV in Chinese HCV genotype 1b patients. PLoS One. 2016; 11(11): e0165658. https://doi.org/10.1371/journal.pone.0165658
  37. Palanisamy N., Kalaghatgi P., Akaberi D., Lundkvist Å., Chen Z.W., Hu P., et al. Worldwide prevalence of baseline resistance-associated polymorphisms and resistance mutations in HCV against current direct-acting antivirals. Antivir. Ther. 2018; 23(6): 485–93. https://doi.org/10.3851/IMP3237
  38. Ikeda H., Watanabe T., Shimizu H., Hiraishi T., Kaneko R., Baba T., et al. Efficacy of ledipasvir/sofosbuvir with or without ribavirin for 12 weeks in genotype 1b HCV patients previously treated with a nonstructural protein 5A inhibitor-containing regimen. Hepatol. Res. 2018; 48(10): 802–9. https://doi.org/10.1111/hepr.13074
  39. Wang G.P., Terrault N., Reeves J.D., Liu L., Li E., Zhao L., et al. Prevalence and impact of baseline resistance-associated substitutions on the efficacy of ledipasvir/sofosbuvir or simeprevir/sofosbuvir against GT1 HCV infection. Sci. Rep. 2018; 8(1): 3199. https://doi.org/10.1038/s41598-018-21303-2
  40. Kati W., Koev G., Irvin M., Beyer J., Liu Y., Krishnan P., et al. In vitro activity and resistance profile of dasabuvir, a nonnucleoside hepatitis C virus polymerase inhibitor. Antimicrob. Agents Chemother. 2015; 59(3): 1505–11. https://doi.org/10.1128/AAC.04619-14
  41. Di Maio V.C., Cento V., Lenci I., Aragri M., Rossi P., Barbaliscia S., et al. Multiclass HCV resistance to direct-acting antiviral failure in real-life patients advocates for tailored second-line therapies. Liver Int. 2017; 37(4): 514–28. https://doi.org/10.1111/liv.13327
  42. European Association for the Study of the Liver. EASL Recommendations on Treatment of Hepatitis C 2018. J. Hepatol. 2018; 69(2): 461–511. https://doi.org/10.1016/j.jhep.2018.03.026
  43. Popping S., Cento V., Seguin-Devaux C., Boucher C.A.B., de Salazar A., Heger E., et al. The European prevalence of resistance associated substitutions among direct acting antiviral failures. Viruses. 2022; 14(1): 16. https://doi.org/10.3390/v14010016
  44. Barth R.E., Huijgen Q., Tempelman H.A., Mudrikova T., Wensing A.M., Hoepelman A.I. Presence of occult HBV, but near absence of active HBV and HCV infections in people infected with HIV in rural South Africa. J. Med. Virol. 2011; 83(6): 929–34. https://doi.org/10.1002/jmv.22026
  45. Tramuto F., Maida C.M., Colomba G.M., Di Carlo P., Vitale F. Prevalence of occult hepatitis B virus infection in a cohort of HIV-positive patients resident in Sicily, Italy. Biomed. Res. Int. 2013; 2013: 859583. https://doi.org/10.1155/2013/859583
  46. Laguno M., Larrousse M., Blanco J.L., Leon A., Milinkovic A., Martínez-Rebozler M., et al. Prevalence and clinical relevance of occult hepatitis B in the fibrosis progression and antiviral response to INF therapy in HIV-HCV-coinfected patients. AIDS Res. Hum. Retroviruses. 2008; 24(4): 547–53. https://doi.org/10.1089/aid.2007.9994
  47. Panigrahi R., Majumder S., Gooptu M., Biswas A., Datta S., Chandra P.K., et al. Occult HBV infection among anti-HBc positive HIV-infected patients in apex referral centre, Eastern India. Ann. Hepatol. 2012; 11(6): 870–5.
  48. Hann HW., Gregory V.L., Dixon J.S., Barker R.F. A review of the one-year incidence of resistance to lamivudine in the treatment of chronic hepatitis B. Hepatol. Int. 2008; 2(4): 440–56. https://doi.org/10.1007/s12072-008-9105-y
  49. Elpaeva E.A., Pisareva M.M., Nikitina O.E., Kizhlo S.N., Grudinin M.P., Dudanova O.P. Role of hepatitis B virus mutant forms in progressive course of chronic hepatitis B. Uchenye zapiski Petrozavodskogo gosudarstvennogo universiteta. 2014; (6): 41–6. (in Russian)
  50. Kozhanova T.V., Il’chenko L.Yu., Isaeva O.V., Alekseeva M.N., Saryglar A.A., Mironova N.I., et al. Circulation of hepatitis B virus variants carrying mutations in the polymerase gene among HBV-infected and HBV/HIV-coinfected patients. Sovremennye tekhnologii v meditsine. 2013; 5(2): 60–4. (in Russian)
  51. Isaeva O.V., Kyuregyan K.K. Viral hepatitis delta: an underestimated threat. Infektsionnye bolezni: novosti, mneniya, obuchenie. 2019; 8(2): 72–9. https://doi.org/10.24411/2305-3496-2019-12010 (in Russian)

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Distribution of HBV and HCV markers among different age groups of HIV infected persons.

Download (292KB)
Indexing metadata
3. Fig. 2. Phylogenetic tree constructed by the maximum-likelihood method for the nucleotide sequences of HCV NS5b gene fragments (380 nt) of HCV isolates obtained from HIV infected persons from the Novosibirsk region (marked in bold type and code Nsk). The letter R marks HCV variants with the C316N mutation associated with resistance to treatment with NS5b inhibitors (sofosbuvir, dacbuvir).

Download (306KB)
Indexing metadata
4. Fig. 3. Phylogenetic analysis of the studied nucleotide sequences of HCV NS5b gene fragments (265 nt) of HCV isolates obtained from HIV infected patients from the Novosibirsk region (marked in red bold type and code Nsk) with HCV variants that previously circulated in Russia and neighboring countries. Blue color indicates HCV variants circulating in Western Siberia; purple color indicates HCV variants circulating in Eastern Siberia and the Far East. Variants of subgenotype 1a, clustered into a separate clade, are marked with a red rectangle.

Download (630KB)
Indexing metadata
5. Fig. 4. Phylogenetic tree constructed by the maximum-likelihood method for the nucleotide sequences of HBV pol gene fragments (1200 nt) of HBV isolates obtained from HIV infected persons from the Novosibirsk region (marked in bold type and code Nsk).

Download (314KB)
Indexing metadata
6. Fig. 5. Phylogenetic tree constructed by the maximum likelihood method for complete genome nucleotide sequences of HDV isolates (Nsk-D1 and Nsk-D2) obtained from HIV infected persons from the Novosibirsk region.

Download (363KB)
Indexing metadata

Copyright (c) 2022 Kartashov M.Y., Svirin K.A., Krivosheina E.I., Chub E.V., Ternovoi V.A., Kochneva G.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».