THE PREVALENCE OF OCCULT HEPATITIS B AMONG HBSAG-NEGATIVE PERSONS WITH HIV IN VELIKY NOVGOROD

Aim: to estimate the prevalence of the occult hepatitis B virus among HIV-infected patients with the virological ineffectiveness of antiretroviral therapy in Veliky Novgorod. Materials and methods. Blood plasma samples from 76 HBsAg-negative HIVinfected patients with virological inefficiency of antiretroviral therapy from Veliky Novgorod were used in the work. For the detection of the hepatitis B virus, nucleic acids were isolated using the commercial kit AmplePrime Ribo-prep. For amplification and sequencing, overlapping pairs of specific primers were used, jointly flanking a 1475 base pair fragment including the 1169 base pair Pre-S1/Pre-S2/S region recommended for genotyping the hepatitis B virus. Results. Among 76 samples of hepatitis B virus DNA, 44 samples were found, which was 57,89%. None of the patients had HBsAg, and 6 patients (13,63%) had HBcor IgG and HBe IgG antibodies. On the basis of phylogenetic analysis, it was shown that only genotype D, which is the most common genotype of the hepatitis B virus in the Russian Federation, was detected in the examined group. The subgenotype D2 (47,72%) prevailed in comparison with the subgenotype D1 (34,09%) and the subgenotype D3 (18,18%). The distribution possible ways of the subgenotype D1 hepatitis B virus, which is uncharacteristic for the region, are discussed. Only one isolate of hepatitis B virus with mutations of drug resistance to nucleotide / nucleoside analogue therapy has been identified — amino acid substitution in the polymerase gene of the virus (L180M, M204V) associated with the development of resistance to lamivudine, entecavir, telbivudine and tenofovir. Conclusion. The high prevalence of occult hepatitis B among HIVinfected patients indicates a lack current tests for the diagnosis of chronic HBV infections. The identification of occult hepatitis B in HIV-infected individuals seems appropriate for timely treatment of patients and requires the use more sensitive methods.

1. Yim H.J., Lok A.S. Natural history of chronic hepatitis B virus infection: what we knew in 1981 and what we know in 2005. Hepatology, 2006, Vol. 43, No. Suppl. 1, pp. S173–S181. URL: DOI: 10.1002/hep.20956.

2. Raimondo G., Allain J. P., Brunetto M.R., Buendia M.A., Chen D.S., Colombo M., Craxi A., Donato F., Ferrari C., Gaeta G.B., Gerlich W.H., Levrero M., Locarnini S., Michalak T., Mondelli M.U., Pawlotsky J.M., Pollicino T., Prati D., Puoti M., Samuel D., Shouval D., Smedile A., Squadrito G., Trepo C., Villa E., Will H., Zanetti A.R., Zoulim F. Statements from the Taormina expert meeting on occult hepatitis B virus infection. J. Hepatol., 2008, Vol. 49, pp. 652–657. URL: DOI: 10.1016/j.jhep.2008.07.014.

3. Semenov A.V., Ostankova Yu.V., Faizullaev Kh.N., Kazakova E.I., Kozlov A.V., Musabaev E.I., Totolyan Areg A. HBV covalently closed circular DNA as a marker of prevalence of occult hepatitis В in patients with HBV, HDV and HCV infection in Uzbekistan. Journal of Microbiology, Epidemiology and Immunobiology, 2016, No. 5, pp. 43–49 (In Russ.)

4. Samal J., Kandpal M., Vivekanandan P. Molecular mechanisms underlying occult hepatitis B virus infection. Clin. Microbiol. Rev., 2012, Vol. 25, pp. 142–163. URL: DOI: 10.1128/CMR.00018-11.

5. Joint United Nations Programme on HIV/AIDS, United Nations. Global Report: UNAIDS Report on the Global AIDS epidemic. Geneva: UNAIDS, 2012, 212 p. URL: http://www.unaids.org/en/resources/documents/2012/20121120_UNAIDS_Global_Report_2012.

6. Prevention and control of viral hepatitis infection: frame work for global action. Geneva: WHO, 2012. URL: http://www.who.int/hiv/pub/hepatitis/Framework/en/.

7. Dadasheva A.E., Mamadov M.K., Mikhailov M.I. About two types of groups with high risk of infection with hepatitis b and C viruses: epidemiological and clinical significance. In the World of Viral Hepatitis, 2011, No. 1, pp. 12–14 (In Russ.)].

8. Argani H., Akhtarishojaie E. Levamizole enhances immune responsiveness to intra-dermal and intra-muscular hepatitis B vaccination in chronic hemodialysis patients. J. Immune Based Ther. Vaccines, 2006, Vol. 4, pp. 3. URL: DOI: 10.1186/1476-8518-4-3.

9. Vallet-Pichard A., Pol S. Natural history and predictors of severity of chronic hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection. J. Hepatol., 2006, Vol. 44, No. 1, pp. S28–S34. URL: DOI: 10.1016/j.jhep.2005.11.008.

10. Osborn M.K., Guest J.L., Rimland D. Hepatitis B virus and HIV coinfection: relationship of different serological patterns to survival and liver disease. HIV Med., 2007, Vol. 8, No. 5, pp. 271–279. URL: DOI: 10.1111/j.1468-1293.2007.00469.x.

11. Ramezani A., Banifazl M., Mohraz M., Rasoolinejad M., Aghakhani A. Occult hepatitis B virus infection: A major concern in HIV-infected patients: Occult HBV in HIV. Hepat. Mon., 2011, Vol. 11, No. 1, pp. 7–10.

12. Brichler S., Lagathu G., Chekaraou M.A., Le Gal F., Edouard A., Dény P., Césaire R., Gordien E. African, Amerindian and European hepatitis B virus strains circulate on the Caribbean Island of Martinique. J. Gen. Virol., 2013, Vol. 94 (Pt. 10), pp. 2318–2329. URL: DOI: 10.1099/vir.0.055459-0.

13. Kumar S., Stecher G., Tamura K. MEGA7: Molecular Evolutionary Genetics Analysis version 7.0 for bigger datasets. Mol. Biol. Evol., 2016, Vol. 33, No. 7, pp. 1870–1874. URL: DOI: 10.1093/molbev/msw054.

14. Coffin C.S., Mulrooney-Cousins P.M., Osiowy C., van der Meer F., Nishikawa S., Michalak T.I., van Marle G., Gill M.J. Virological characteristics of occult hepatitis B virus in a North American cohort of human immunodeficiency virus type 1-positive patients on dual active anti-HBV/HIV therapy. J. Clin. Virol., 2014, Vol. 60, No. 4, pp. 347–353. URL: DOI: 10.1016/j.jcv.2014.04.021.

15. Gupta S., Singh S. Occult Hepatitis B Virus infection in ART-Naïve HIV-Infected patients seen at a tertiary care center in North India. BMC Infect. Dis., 2010, Vol. 10, pp. 53. URL: DOI: 10.1186/1471-2334-10-53.

16. Honarmand A., Pourahmad M., Solhjoo K., Kohan M., Davami M.H., Mostafavi Zadeh S.K. Occult hepatitis B demonstrated by anti-HBc and HBV DNA in HIV-positive patients. Rep. Biochem. Mol. Biol., 2014, Vol. 3, No. 1, pp. 38–42.

17. Alvarez-Munoz M.T., Maldonado-Rodriguez A., Rojas-Montes O., Torres-Ibarra R., Gutierrez-Escolano F., Vazquez-Rosales G., Gomez A., Munoz O., Torres J., Lira R. Occult hepatitis B virus infection among Mexican human immunodeficiency virus-1-infected patients. World J. Gastroenterol., 2014, Vol. 20, No. 37, pp. 13 530–13 537. URL: DOI: 10.3748/wjg.v20.i37.13530.

18. Bautista-Amorocho H., Castellanos-Domínguez Y.Z., Rodríguez-Villamizar L.A., Velandia-Cruz S.A., Becerra-Peña J.A., Farfán-García A.E. Epidemiology, risk factors and genotypes of HBV in HIV-infected patients in the northeast region of Colombia: high prevalence of occult hepatitis B and F3 subgenotype dominance. PLoS One, 2014, Vol. 9, No. 12, pp. e114 272. URL: DOI: 10.1371/journal.pone.0114272.

19. Cohen Stuart J.W., Velema M., Schuurman R., Boucher C.A., Hoepelman A.I. Occult hepatitis B in persons infected with HIV is associated with low CD4 counts and resolves during antiretroviral therapy. J. Med. Virol., 2009, Vol. 81, No. 3, pp. 441–445. URL: DOI: 10.1002/jmv.21422.

20. Fabris P., Biasin M.R., Giordani M.T., Berardo L., Menini V., Carlotto A., Miotti M.G., Manfrin V., Baldo V., Nebbia G., Infantolino D. Impact of occult HBV infection in HIV/HCV co-infected patients: HBV-DNA detection in liver specimens and in serum samples. Curr. HIV Res., 2008, Vol. 6, No. 2, pp. 173–179. URL: DOI : 10.2174/157016208783885029.

21. Esmail M.A., Mahdi W.K., Khairy R.M., Abdalla N.H. Genotyping of occult hepatitis B virus infection in Egyptian hemodialysis patients without hepatitis C virus infection. J. Infect. Public Health, 2016, Vol. 9, No. 4, pp. 452–457. URL: DOI: 10.1016/j.jiph.2015.11.018.

22. Kim K.H., Chang H.Y., Park J.Y. Spontaneous HBsAg loss in Korean patients: relevance of viral genotypes, S gene mutations, and covalently closed circular DNA copy numbers. Clin. Mol. Hepatol., 2014, Vol. 20, No. 3, pp. 251–260. URL: DOI: 10.3350/cmh.2014.20.3.251.

23. Ostankova Yu.V., Semenov A.V., Burkitbayev Zh.K., Savchuk T.N., Totolian A.A. Genetic variants of hepatitis B virus in primary donors in Astana, Kazakhstan. Infection and Immunity, 2016, Vol. 6, No. 4, pp. 359–365 (In Russ.)

24. Wiersma S.T., McMahon B., Pawlotsky J.-M., Thio C.L., Thursz Ma., Gee Lim S., Ocama P., Esmat G., Maimuna M., Bell D., Vitoria M., Eramova I., Lavanchy D., Dusheiko G. Treatment of chronic hepatitis B virus infection in resource-constrained settings: expert panel consensus. Liver Int., 2011, Vol. 31, Issue 6, pp. 755–761. URL: DOI: 10.1111/j.1478-3231.2010.02373.x.

25. Sagnelli E., Pisaturo M., Martini S., Filippini P., Sagnelli C., Coppola N. Clinical impact of occult hepatitis B virus infection in immunosuppressed patients. World J. Hepatol., 2014, Vol. 6, No. 6, pp. 384–393. URL: DOI: 10.4254/wjh.v6.i6.384.