TY - JOUR

T1 - Genetic Diversity of the Hepatitis B Virus in Five Russian Regions during the Universal Vaccination Program: Assessing the Impact of New Selective Pressures on the Spectrum of Genetic and Serological Variants

AU - Мануйлов, Виктор Александрович

AU - Сергеева, Е.И.

AU - Будай, Г.И.

AU - Тищенко, Т.Н.

AU - Морозова, С.А.

AU - Чуланов, Владимир Петрович

AU - Кюрегян, Карен Каренович

AU - Аглетдинов, Эдуард Феликсович

AU - Безуглова (Цой), Людмила Вячеславовна

AU - Нетёсов, Сергей Викторович

N1 - The work was carried out mainly without special financial support, using the existing basic funding of the participating organizations. The participation of V. A. Manuylov and S. V. Netesov was supported within the framework of a state assignment for financing research at Novosibirsk State University, no. FSUS-2020-0035.

PY - 2025/3

Y1 - 2025/3

N2 - Since the introduction of the universal hepatitis B vaccination program in Russia in 2001, the incidence of acute hepatitis B has dropped from 35.3 to 0.3 cases per 100 thousand people annually, while that of chronic hepatitis B (including new HBV carriers) has declined from 105.6 to 16.8 cases per 100 thousand. The proportion of HBsAg-positive carriers in the general population has decreased from 1.8–4.6% in the 1990s to 0.8 ± 0.1% by 2020. An important question remains whether any HBV genetic variants have gained an evolutionary advantage under this selective pressure. Aim. To evaluate changes in the spectrum of genetic and serological variants of HBV circulating in five regions of Russia—Chukotka, Tyva, Yakutia, Moscow, and Khabarovsk—over 10 to 20 years of observation. Results and Discussion. In Chukotka, the proportion of the dominant subgenotype D3 (mainly the HBsAg subtype ayw2) fluctuated from 44.3 (in 1997) to 58.1% (2008), C2 (adrq+) from 16.4 (1997) to 37.1% (2008), D2 (ayw3) from 3.2 (2008) to 23% (1997), D1 (ayw2) from 1.6 (2008) to 11.5% (1997), and A2 (adw2) from 0 (2008) to 4.9% (1997). In Tyva, the prevalence of D1 ranged from 57.4 (2021) to 67.6% (2008–2009), D2 from 13.2 (2008–2009) to 38.3% (2021), D3 from 0 (2021) to 16.2% (2008–2009), and A2 from 2.9 (2008–2009) to 4.3% (2021). In Yakutia, D3 was from 24.1 (2022) to 45.5% (2004–2008), A2 from 36.8 (2018) to 43.1% (2022), D2 from 4.5 (2004–2008) to 13.1% (2022), C2 from 5.3 (2018) to 11.7% (2022), and D1 from 4.5 (2004–2008) to 6.6% (2022). In Moscow, D3 was from 25 (2020) to 49.1 (2008–2009), D1 from 16.4 (2008–2009) to 41.2% (2020), D2 from 24.3 (2020) to 25.5% (2008–2009), and A2 from 5.3 (2008–2009) to 8.1% (2020). Finally, in Khabarovsk, the proportion of D2 ranged from 23.1 (2021) to 46.9% (2003–2008), D3 from 27.8 (2015) to 40.6% (2003–2008), D1 from 3.1 (2003–2008) to 24.6% (2021), A2 from 5.6 (2015) to 10.8% (2021), and C2 from 3.1 (2003–2008, 2021) to 5.6% (2015). Despite shifts in the proportions of distinct variants, the overall spectrum of HBV types circulating within each region has remained largely unchanged over the 10- to 20-year observation period. Conclusions. None of the HBV variants have shown any clear evolutionary advantage against the backdrop of the viral population’s decline over the past decades. This may suggest that HBV is genetically conservative and lacks the capacity for rapid evolutionary change, increasing the chances of future eradication through continued vaccination efforts.

AB - Since the introduction of the universal hepatitis B vaccination program in Russia in 2001, the incidence of acute hepatitis B has dropped from 35.3 to 0.3 cases per 100 thousand people annually, while that of chronic hepatitis B (including new HBV carriers) has declined from 105.6 to 16.8 cases per 100 thousand. The proportion of HBsAg-positive carriers in the general population has decreased from 1.8–4.6% in the 1990s to 0.8 ± 0.1% by 2020. An important question remains whether any HBV genetic variants have gained an evolutionary advantage under this selective pressure. Aim. To evaluate changes in the spectrum of genetic and serological variants of HBV circulating in five regions of Russia—Chukotka, Tyva, Yakutia, Moscow, and Khabarovsk—over 10 to 20 years of observation. Results and Discussion. In Chukotka, the proportion of the dominant subgenotype D3 (mainly the HBsAg subtype ayw2) fluctuated from 44.3 (in 1997) to 58.1% (2008), C2 (adrq+) from 16.4 (1997) to 37.1% (2008), D2 (ayw3) from 3.2 (2008) to 23% (1997), D1 (ayw2) from 1.6 (2008) to 11.5% (1997), and A2 (adw2) from 0 (2008) to 4.9% (1997). In Tyva, the prevalence of D1 ranged from 57.4 (2021) to 67.6% (2008–2009), D2 from 13.2 (2008–2009) to 38.3% (2021), D3 from 0 (2021) to 16.2% (2008–2009), and A2 from 2.9 (2008–2009) to 4.3% (2021). In Yakutia, D3 was from 24.1 (2022) to 45.5% (2004–2008), A2 from 36.8 (2018) to 43.1% (2022), D2 from 4.5 (2004–2008) to 13.1% (2022), C2 from 5.3 (2018) to 11.7% (2022), and D1 from 4.5 (2004–2008) to 6.6% (2022). In Moscow, D3 was from 25 (2020) to 49.1 (2008–2009), D1 from 16.4 (2008–2009) to 41.2% (2020), D2 from 24.3 (2020) to 25.5% (2008–2009), and A2 from 5.3 (2008–2009) to 8.1% (2020). Finally, in Khabarovsk, the proportion of D2 ranged from 23.1 (2021) to 46.9% (2003–2008), D3 from 27.8 (2015) to 40.6% (2003–2008), D1 from 3.1 (2003–2008) to 24.6% (2021), A2 from 5.6 (2015) to 10.8% (2021), and C2 from 3.1 (2003–2008, 2021) to 5.6% (2015). Despite shifts in the proportions of distinct variants, the overall spectrum of HBV types circulating within each region has remained largely unchanged over the 10- to 20-year observation period. Conclusions. None of the HBV variants have shown any clear evolutionary advantage against the backdrop of the viral population’s decline over the past decades. This may suggest that HBV is genetically conservative and lacks the capacity for rapid evolutionary change, increasing the chances of future eradication through continued vaccination efforts.

UR - https://www.scopus.com/pages/publications/105011935623

UR - https://elibrary.ru/item.asp?id=82285189

U2 - 10.3103/S0891416825700053

DO - 10.3103/S0891416825700053

M3 - Article

VL - 40

SP - 37

EP - 52

JO - Molecular Genetics, Microbiology and Virology

JF - Molecular Genetics, Microbiology and Virology

SN - 0891-4168

IS - 1

M1 - 5

ER -