Introduction. A sharp increase in the registered incidence of chronic hepatitis C, exceeding the average country level by more than 3 times, was noted in Omsk Region since 2023. The objective of the study was to answer the question of whether the observed increase in incidence is a consequence of the recent sharp increase in cases of hepatitis C virus (HCV) transmission, using molecular genetic analysis. Materials and methods. Amplification of HCV core/E1 fragment and Bayesian phylogenetic analysis of corresponding nucleotide sequences were performed for serum samples from 344 patients with chronic hepatitis C diagnosed in 2022–2023, which accounted for 12.6% of all chronic hepatitis C cases diagnosed during this period in Omsk Region (n = 2730). Results. Phylogenetic analysis demonstrated the presence of regional HCV clusters formed in 1990–2000s (95% HPD 1980–2014). The majority (86.0%, 295 out of 343) of HCV genotype 1a, 1b, 2a, 2c, 2k and 3a sequences isolated in 2023–2024 belong to different lineages circulating in the region for at least 10 years, which, together with the absence of large, homogeneous clusters with a recent tMRCA suggests the absence of a recent epidemiological link between these HCV cases. However, 12 (3.5%) sequences formed pairs with divergence in 2021–2023 (95% HPD 2018–2024), which indicates recent infection and suggests the presence of an epidemiological link between these cases of infection. Such pairs were identified for HCV genotypes 1a, 1b, 2a and 3a. Conclusion. The observed upsurge in chronic hepatitis C incidence in Omsk Region apparently reflects the accumulated number of cases of HCV infection in the region resulted from transmissions occurred 10–20 or more years ago, and is a consequence of the increase in the HCV testing coverage. With an increase in the testing rates, especially in vulnerable groups where a significant number of undetected HCV infections are concentrated, an increase in the incidence of chronic hepatitis C can be expected in other regions of the country.

Identifying population groups at greatest risk of hepatitis C virus (HCV) infection is essential for targeting screening and treatment. We analyzed the seroprevalence of antibodies to HCV (anti-HCV) and HCV RNA in serum samples from 37,291 conditionally healthy volunteers collected between 2018 and 2022, and from 4764 individuals sampled in 2008, totaling 42,055 participants. In 2018–2022, anti-HCV prevalence varied by region, ranging from 1.1 to 1.4% in Belgorod, Moscow, and St. Petersburg to 1.8–2.1% in Dagestan, Tatarstan, Novosibirsk, Tyva, and southern Yakutia, and reaching 3.4–5.2% in Khabarovsk and the Arctic zone of Yakutia. In 2008, prevalence in Moscow, Rostov, Sverdlovsk, Tyva, and Yakutia ranged from 1.7% to 3.3%. A significant decline over time was observed: from a mean of 2.6 ± 0.5% in 2008 to 1.9 ± 0.1% in 2018–2022 (p < 0.01). In recent years, men were more frequently anti-HCV-positive than women (2.5 ± 0.2% vs. 1.5 ± 0.2%, p < 0.01), whereas no sex differences were noted in 2008. The age of a sharp prevalence increase shifted from the 20–29 cohort in 2008 to the 30–39 cohort in 2018–2022. Based on the demographic structure, we estimate ~3.23 million anti-HCV carriers in Russia. HCV RNA was detectable in only one-third of seropositive individuals, identifying them as candidates for antiviral therapy. Thus, in contemporary Russia, men aged over 30 years have the highest risk of HCV infection and should be prioritized for targeted screening.

Identifying population groups at greatest risk of hepatitis C virus (HCV) infection is essential for targeting screening and treatment. We analyzed the seroprevalence of antibodies to HCV (anti-HCV) and HCV RNA in serum samples from 37,291 conditionally healthy volunteers collected between 2018 and 2022, and from 4,764 individuals sampled in 2008, totaling 42,055 participants. In 2018–2022, anti-HCV prevalence varied by region, ranging from 1.1–1.4% in Belgorod, Moscow, and St. Petersburg to 1.8–2.1% in Dagestan, Tatarstan, Novosibirsk, Tyva, and southern Yakutia, and reaching 3.4–5.2% in Khabarovsk and the Arctic zone of Yakutia. In 2008, prevalence in Moscow, Rostov, Sverdlovsk, Tyva, and Yakutia ranged from 1.7% to 3.3%. A significant decline over time was observed: from a mean of 2.6 ± 0.5% in 2008 to 1.9 ± 0.1% in 2018–2022 (p < 0.01). In recent years, men were more frequently anti-HCV–positive than women (2.5 ± 0.2% vs 1.5 ± 0.2%, p < 0.01), whereas no sex differences were noted in 2008. The age of sharp prevalence increase shifted from the 20–29 cohort in 2008 to the 30–39 cohort in 2018–2022. Based on demographic structure, we estimate ~3.23 million anti-HCV carriers in Russia. HCV RNA was detectable in only one-third of seropositive individuals, identifying them as candidates for antiviral therapy. Thus, in contemporary Russia, men over 30 years have the highest risk of HCV infection and should be prioritized for targeted screening.

Transfusion-transmitted hepatitis E virus (HEV) infection is an increasing concern in many countries. We investigated the detection rate of HEV viremia in blood donors in Russia. A total of 20,405 regular repetitive voluntary non-renumerated blood donors from two regions (Moscow and Belgorod) were screened for HEV RNA using the cobas® HEV test in mini-pools of six plasma samples. Samples from each reactive pool were tested individually. The average HEV RNA prevalence was 0.024% (95% CI: 0.01–0.05%), or 1 case per 4081 donations. No statistically significant differences in HEV RNA prevalence were observed between the two study regions. The PCR threshold cycle (Ct) values ranged from 25.0 to 40.5 in reactive pools, and from 20.9 to 41.4 in reactive plasma samples when tested individually. The HEV viremic donors had different antibody patterns. Two donor samples were reactive for both anti-HEV IgM and IgG antibodies, one sample was reactive for anti-HEV IgM and negative for anti-HEV IgG, and two samples were seronegative. At follow-up testing 6 months later, on average, four donors available for follow-up had become negative for HEV RNA and positive for anti-HEV IgG. The HEV ORF2 sequence belonging to HEV-3 sub-genotype 3a was obtained from one donor sample. The sequencing failed in the other four samples from viremic donors, presumably due to the low viral load. In conclusion, the HEV RNA detection rate in blood donors in Russia corresponds with data from other European countries, including those that implemented universal donor HEV screening. These data support the implementation of HEV RNA donor screening to reduce the risk of transfusion-transmitted HEV infection in Russia.

The aim is to determine the dynamic changes in the prevalence of hepatitis C virus (HCV) infection among various age groups of the conditionally healthy population of the Tyva Republic over the past 11 years.Material and methods. 1163 serum samples collected in 2019 from the healthy volunteers living in the Tyva Republic of were tested for HCV markers. The study included people of 10 age cohorts: less than 1 year, 1-4, 5-9, 10-14, 15-19, 20-29, 30-39, 40-49, 50-59 years, and 60 years or older. Anti-HCV antibodies were detected using commercially available enzyme immunoassay. HCV RNA was detected in anti-HCV positive samples by means of RT-PCR. The dynamic changes in HCV prevalence were assessed based on a comparison of the results with data of the seroservey of the same design conducted in this region in 2008 in similar age cohorts of healthy volunteers (n=910).Results and discussion. The prevalence of anti-HCV antibodies among general population of the Tyva Republic in 2019 was 2.0%. This indicator slightly decreased by 1.7 times over 10 years (3.3% in 2008, p =0.1629). The prevalence of active HCV infection in the Tyva Republic also decreased not significantly (1.1% in 2019 vs. 1.3% in 2008, p = 0.6901). The proportion of people with active infection among anti-HCV positives in 2019 was 56.5%.The decrease in the prevalence of HCV infection over 11 years was associated with a significant reduction in the detection rates of hepatitis C markers in age cohort 40-49 years (0.9% in 2019 vs. 3.6% in 2008 for HCV RNA, p<0.05, and 1.8% in 2019 vs. 9.1% in 2008 for anti-HCV, p<0.05, respectively). The highest rates of detection of anti-HCV and HCV RNA were observed among participants aged 60 years and over (8.0% and 7.0%, respectively, in 2019 and 11.0 and 6.3%, respectively, in 2008), which significantly exceeded detection rates in other age groups, both in 2008 and 2019 (<0.05).Conclusion. A decrease in the prevalence of HCV infection in general population of the Tyva Republic was observed over last 11 years, primarily due to a decrease in the proportion of unidentified cases of infection among people aged 40-49 years. At the same time, the proportion of unidentified cases of HCV infection in persons aged 60 years and older remains consistently high, which is apparently due to insufficient screening coverage in this age cohort. This age-associated risk cohort should be benefited from the inclusion in HCV screening program.

The indigenous populations of the Arctic regions of Russia experience the lowest coverage of health-related services. We assessed the prevalence of hepatitis A, B, C, D and E viruses (HAV, HBV, HCV, HDV and HEV) among 367 healthy adult Native people of the Arctic zone of Yakutia. The HAV seroprevalence was above and increased with age. The anti-HEV IgM and IgG antibody detection rates were 4.1% and 2.5%, respectively. The average HBsAg detection rate was 4.6%, with no positive cases identified in participants aged under 30 years, confirming the effectiveness of the newborn vaccination program that began in 1998. Anti-HDV antibodies were detected in 29.4% of HBsAg-positive cases. The anti-HCV and HCV RNA detection rates peaked in the age cohort of 50–59 years (10.8% and 3.9%). No statistically significant gender differences in the prevalence of different viral hepatitis were observed. The time-scaled phylogenetic analysis demonstrated that all HBV genotype A and D strains isolated in this study were autochthonous and had an estimated most common recent ancestor (MCRA) age of around the 11th to 14th century. Unlike HBV, the HCV strains of subtypes 1b, 2a and 2k/1b were introduced from other regions of Russia in the 1980s and 1990s. The HCV 1b sequence analysis revealed a series of transmission events. In conclusion, these data emphasize the urgent need for expanded viral hepatitis screening and care programs in the indigenous populations of the Arctic zone of Yakutia.

Since 2012, universal single-dose HAV vaccination in children aged 3 years and older has been implemented in the Tyva Republic, a region of the Russian Federation. The aim of this prospective non-interventional observational single-center study was to determine the immunological and epidemiological effectiveness of single-dose vaccination against hepatitis A 9 to 11 years after its implementation. The anti-HAV IgG antibodies were determined in two independent cohorts of children who were vaccinated with a single dose of monovalent pediatric inactivated vaccine (HAVRIX® 720 EU) in Tyva in 2012 and recruited 9 years (Year 9 Cohort) and 11 years (Year 11 Cohort) after immunization. The seroprotection rates defined as anti-HAV antibody concentrations ≥10 mIU/mL reached 99.4% (95% CI: 98.2–99.9% [501/504]) in the Year 9 Cohort, but decreased significantly to 75.4% (95% CI: 73.0–77.6% [1006/1335]) in the Year 11 Cohort (p < 0.0001). The anti-HAV geometric mean concentrations decreased from 1446.3 mIU/mL (95% CI: 1347.1–1545.4 mIU/mL) in the Year 9 Cohort to 282.6 mIU/mL (95% CI: 203.8–360.8, p < 0.0001) in the Year 11 Cohort. The HAV vaccination program resulted in zero rates of hepatitis A incidence in the Tyva Republic since 2016. However, the limited monitoring of HAV RNA in sewage and environmental samples demonstrated the ongoing circulation of both the regional epidemic strain of HAV genotype IA and another genotype IA strain imported recently from other parts of the Russian Federation, probably due to subclinical infections in non-vaccinated children under 3 years of age. Taken together, these data indicate the effectiveness of the single-dose HAV vaccination strategy but suggest the need to expand the vaccination program to include children aged 12 months and older to achieve maximum effectiveness.

A neonatal vaccination against the Hepatitis B virus (HBV) infection was initiated in Russia 20 years ago, with catch-up immunization for adolescents and adults under the age of 60 years launched in 2006. Here, we have assessed the humoral immunity to HBV in different regions of Russia, as well as the infection frequency following 20 years of a nationwide vaccination campaign. We have also evaluated the role of immune-escape variants in continuing HBV circulation. A total of 36,149 healthy volunteers from nine regions spanning the Russian Federation from west to east were tested for HBV surface antigen (HBsAg), antibodies to HBV capsid protein (anti-HBc), and antibodies to HBsAg (anti-HBs). HBV sequences from 481 chronic Hepatitis B patients collected from 2018–2022 were analyzed for HBsAg immune-escape variants, compared with 205 sequences obtained prior to 2010. Overall, the HBsAg detection rate was 0.8%, with this level significantly exceeded only in one study region, the Republic of Dagestan (2.4%, p < 0.0001). Among the generation vaccinated at birth, the average HBsAg detection rate was below 0.3%, ranging from 0% to 0.7% depending on the region. The anti-HBc detection rate in subjects under 20 years was 7.4%, indicating ongoing HBV circulation. The overall proportion of participants under 20 years with vaccine-induced HBV immunity (anti-HBs positive, anti-HBc negative) was 41.7% but below 10% in the Tuva Republic and below 25% in the Sverdlovsk and Kaliningrad regions. The overall prevalence of immune-escape HBsAg variants was 25.2% in sequences obtained from 2018–2022, similar to the prevalence of 25.8% in sequences collected prior to 2010 (p > 0.05). The population dynamics of immune-escape variants predicted by Bayesian analysis have remained stable over the last 20 years, indicating the absence of vaccine-driven positive selection. In contrast, the wild-type HBV population size experienced a rapid decrease starting in the mid-1990s, following the introduction of mass immunization, but it subsequently began to recover, reaching pre-vaccination levels by 2020. Taken together, these data indicate that it is gaps in vaccination, and not virus evolution, that may be responsible for the continued virus circulation despite 20 years of mass vaccination.

The factors influencing hepatitis E virus (HEV) circulation remain largely unexplored. We investigated HEV seroprevalence in humans and the prevalence of infection in farm pigs and rabbits in different regions of the Russian Federation, as well as the genetic diversity and population dynamics of the HEV. The anti-HEV IgG antibody detection rates in the general population increase significantly with age, from 1.5% in children and adolescents under 20 years old to 4.8% in adults aged between 20 and 59 years old to 16.7% in people aged 60 years and older. HEV seroprevalence varies between regions, with the highest rate observed in Belgorod Region (16.4% compared with the national average of 4.6%), which also has the country’s highest pig population. When compared with the archival data, both increases and declines in HEV seroprevalence have been observed within the last 10 years, depending on the study region. Virus shedding has been detected in 19 out of the 21 pig farms surveyed. On one farm, the circulation of the same viral strain for five years was documented. All the human and animal strains belonged to the HEV-3 genotype, with its clade 2 sequences being predominant in pigs. The sequences are from patients, pigs, and sewage from pig farms clustered together, suggesting a zoonotic infection in humans and possible environmental contamination. The HEV-3 population size that was predicted using SkyGrid reconstruction demonstrated exponential growth in the 1970s–1990s, with a subsequent decline followed by a short rise around the year 2010, the pattern being similar to the dynamics of the pig population in the country. The HEV-3 reproduction number (Re) that was predicted using birth–death skyline analysis has fluctuated around 1 over the past 20 years in Russia but is 10 times higher in Belgorod Region. In conclusion, the HEV-3 circulation varies both geographically and temporally, even within a single country. The possible factors contributing to this variability are largely related to the circulation of the virus among farm pigs.

Aim: The analysis of the incidence of hepatitis B in the Republic of Dagestan (RD) and clinical and epidemiological characteristics of HBV/HDV coinfection in the region. Materials and Methods. The dynamics of the hepatitis B incidence rates and the coverage of vaccination against this infection in the RD in 2008-2022 were analyzed based on the data from of the statistical forms of Rospotrebnadzor. The clinical and epidemiological characteristics of delta hepatitis were analyzed in 371 patients under dispensary observation at the Republican Center for Infectious Diseases named after S.-А.М. Magomedov. Results. Over the past 10 years, the incidence of CHB in the RD has increased more than 4.5 times, from 1.4 per 100 thousand population in 2008 to 6.7 per 100 thousand population in 2022. A decrease in the rates of hepatitis B child immunization in the RD is observed since 2009. Hepatitis B vaccination coverage rates in adult population fell sharply after 2010, both in the RD and in the Russian Federation on average. The frequency of HDV co-infection in persons infected with HBV in the RD is 13.8%, but reaches 15% in some regions of the republic, indicating the moderate level of endemicity. Patients with HBV/HDV coinfection are predominantly males aged 25–45 years with advanced fibrosis or cirrhosis. All cases of HDV infection in the RD are caused by viral genotype 1. Conclusions. The obtained results testify to the significance of the problem of hepatitis B and delta in the RD. The number of identified patients and, accordingly, the rate of co-infection, apparently, will increase with the expansion of screening for markers of HDV infection, when patients who were registered as HBsAg carriers will be examined according to the patient routing guidelines. The late diagnosis of delta hepatitis in RD and the limited possibilities of antiviral therapy are another significant issues.

Rationale: The high prevalence of hepatitis D virus (HDV) infection in the Republic of Dagestan, significantly exceeding that in the European part of the Russian Federation, as well as the limited choice of therapeutic options, have led to the need to analyze the accumulated experience of interferon therapy in the real clinical practice to further select possible treatment regimens. Aim: To evaluate the efficacy of pegylated interferon alpha (Peg-IFN-) in patients with chronic hepatitis D (CHD) in real world clinical practice. Materials and methods: In a retrospective study, the efficacy, safety and tolerability of Peg-IFN- were analyzed in 34 patients with CHD living in the Republic of Dagestan. Main virological parameters (anti-HDV antibodies (anti-HDV), HDV RNA and HBV DNA), alanine aminotransferase levels, changes over time in liver density by elastometry, and clinical parameters (hematology and urine tests, clinical chemistry, thyroid function tests) were assessed at 24 and 48 weeks of therapy, as well as at 48 weeks after its completion. Results: The treatment with Peg-IFN- for 48 weeks resulted in a virological response, defined as a HDV RNA decrease by more than 2 lg copies/mL, in 32% (11/34) of the patients. A sustained virological response, defined as undetectable HDV RNA at 48 weeks after the end of therapy, was not observed in any case. Treatment with interferon was associated with a decrease in liver density by average 4.1 kPa by week 48 on therapy. Normalization of alanine aminotransferase levels after 48 weeks of treatment was observed in 59% (20/34) of the patients; however, sustained biochemical response was achieved in none of them. Serious adverse events of high or moderate severity that resulted in the discontinuation of therapy were observed in 12% (4/34) of the cases. Conclusion: The results obtained indicate low efficacy of Peg-IFN- in the treatment of CHD in the Dagestan patients. Further research is needed to refine optimal interferon therapy regimens, to search for predictors of treatment response, and to evaluate the impact of interferon treatment regimens on the risk of hepatic complications, clinical outcomes, and patient survival. However, the most obvious solution to the problem of CHD therapy is the development and implementation of interferon-free treatment regimens.

The hepatitis delta virus (HDV) is believed to be a vanishing infection in countries with successful hepatitis B virus (HBV) vaccination programs. We assessed the current status of HDV infection in Tuva, a region of the Russia that has been highly endemic for HBV. The proportion of HDV-infected patients among HBsAg-positive patients in the regional registry in 2020 was 32.7% (786/2401). An analysis of the medical records of 514 HDV patients demonstrated that 37.5% (193/514) had liver cirrhosis at the first doctor's visit, and 7.4% of patients lived in families where another family member had HDV. All HDV patients were infected with genotype HDV-1, 94.5% had HBV genotype D, and 5.5% had genotype A. A serosurvey conducted among 1170 healthy volunteers showed that the average detection rate of HBsAg with anti-HDV was 1.0% (95% CI: 0.57-1.81%). No anti-HDV positive samples were detected in participants aged under 30 years. The HBsAg/anti-HDV positivity rate peaked at 7.4% in patients aged 50-59 years, which was significantly higher than in a similar age cohort surveyed in 2008 (1.6%, p < .0001). A Bayesian analysis showed that HDV circulation in Tuva resulted from two waves of introduction, the first in the 1810s (95% HPD: 1741-1834) from Central Asia, and the second in the 1960s (95% HPD: 1953-1979) from Russia. HBV has a much longer history of circulation in Tuva with the MRCA for the predominant genotype HBV-D dated to 972 (95% HPD: 535-1253) for subtype D1, 1274 (95% HPD: 936-1384) for D2, and 1173 (95% HPD: 1005-1618) for D3. A SkyGrid reconstruction of population dynamics showed an increase in the intensity of HDV spread in recent decades. This situation shows the need for HDV screening and prevention measures among people living with HBV.

The factors influencing hepatitis E virus (HEV) circulation remain largely unexplored. We investigated HEV seroprevalence in humans and the prevalence of infection in farm pigs and rabbits in different regions of the Russian Federation, as well as the genetic diversity and population dynamics of HEV. Anti-HEV IgG antibody detection rates in the general population increase significantly with age, from 1.5% in children and adolescents under 20 years old to 4.8% in adults aged between 20 and 59 years old, to 16.7% in people aged 60 years and older. HEV seroprevalence varies between regions, with the highest rate observed in Belgorod Region (16.4% compared with the national average of 4.6%), which also has the country’s highest pig population. When compared with the archival data, both increases and declines in HEV seroprevalence have been observed within the last 10 years, depending on the study region. Virus shedding has been detected in 19 out of the 21 pig farms surveyed. On one farm, circulation of the same viral strain for five years was documented. All human and animal strains belonged to the HEV-3 genotype, with its clade 2 sequences being predominant in pigs. Sequences from patients, pigs, and sewage from pig farms clustered together, suggesting a zoonotic infection in humans and possible environmental contamination. The HEV-3 population size predicted using SkyGrid reconstruction demonstrated exponential growth in the 1970s–1990s, with a subsequent decline followed by a short rise around the year 2010, the pattern being similar to the dynamics of the pig population in the country. The HEV-3 reproduction number (Re) predicted using Birth-Death Skyline analysis has fluctuated around 1 over the past 20 years in Russia, but is 10 times higher in Belgorod Region. In conclusion, HEV-3 circulation varies both geographically and temporally, even within a single country. The possible factors contributing to this variability are largely related to the circulation of the virus among farm pigs.

Background: Hepatitis E virus (HEV) is a major causative agent of acute hepatitis worldwide, prompting continuous HEV vaccine efforts. Vaccine development is hampered by the lack of convenient animal models susceptible to infection with different HEV genotypes. We produced recombinant open reading frame 2 protein (pORF2; p551) of HEV genotype (GT) 3 and assessed its immunogenicity and protectivity against HEV challenge in common marmosets (Callithrix jacchus, CM). Methods: p551 with consensus sequence corresponding to amino acid residues 110-660 of HEV GT3 pORF2 was expressed in E. coli and purified by affinity chromatography. CMs were immunized intramuscularly with 20 lg of p551 VLPs with alum adjuvant (n = 4) or adjuvant alone (n = 2) at weeks 0, 3, 7 and 19. At week 27, p551-immunized and control animals were challenged with HEV GT1 or GT3 and thereafter longitudinally screened for markers of liver function, anti-HEV IgG and HEV RNA in feces and sera. Results: Purified p551 formed VLPs with particle size of 27.71 +/- 2.42 nm. Two immunizations with p551 induced anti-HEV IgG mean titer of 1:1810. Immunized CMs challenged with homologous and heterologous HEV genotype did not develop HEV infection during the follow-up. Control CMs infected with both HEV GT1 and GT3 demonstrated signs of HEV infection with virus shedding and elevation of the levels of liver enzymes. High levels of anti-HEV IgG persisted in vaccinated CMs and control CMs that resolved HEV infection, for up to two years post challenge. Conclusions: CMs are shown to be a convenient laboratory animal model susceptible to infection with HEV GT1 and GT3. Immunization with HEV GT3 ORF2/p551 triggers potent anti-HEV antibody response protecting CMs from homologous and heterologous HEV challenge. This advances p551 in VLPs as a prototype vaccine against HEV. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

The data on hepatitis A virus (HAV) seroprevalence are critical for the implementation of a universal mass vaccination (UMV) strategy. The latter has not been implemented in Russia; however, regional child vaccination programs have been adopted in some parts of the country. The aim of this study is to assess changes in HAV immunity within the last decade in regions of Russia with different vaccination strategies and different vaccination coverage rates. In regions where UMV has not been implemented and HAV vaccination coverage rates do not exceed the national average, the 50% seroprevalence threshold has shifted in the Moscow region from people aged under 40 years in 2008 to people aged over 59 years in 2020, and from people aged under 30 years to people aged over 40 years in the Khabarovsk region. In two regions (Yakutia and Sverdlovsk), a two-dose-based UMV scheme has been in place since 2011 and 2003, respectively, and in Tuva single-dose child immunization was launched in 2012. These regional programs have resulted in a significant increase in HAV seroprevalence in children and adolescents. In Yakutia, 50% herd immunity had been achieved by 2020 in age groups under 20 years, compared to 20–30% seroprevalence rates in 2008. In the Sverdlovsk region, HAV immunity has increased to >65% over the decade in children aged over 10 years, adolescents and young adults, whereas it declined in older age groups. However, a three-fold drop in HAV immunity has occurred in children under 10 years of age, reflecting a significant decline in vaccination coverage. In Tuva, HAV immunity rates in children under 10 years old increased two-fold to exceed 50% by 2020. These data suggest that UMV should be implemented on a national level. Measures to control vaccination coverage and catch-up vaccination campaigns are recommended in order to maintain the effectiveness of existing HAV vaccination programs.

Direct genotyping of hepatitis B virus (HBV) in samples from patients with hepatitis delta can be impossible due to an undetectable concentration of HBV DNA. A sufficient amount of surface HBV protein (HBsAg) in such samples makes it possible to determine HBV genotype using enzyme-linked immunosorbent assay (ELISA) of this antigen with a panel of monoclonal antibodies (MABs). The purpose of this paper is to compare the results of HBV genotyping using an in-house MAB panel with the results of molecular analysis of samples from patients with chronic hepatitis B (CHB) and the determination of HBV genotypes in samples from patients with hepatitis delta. A total of 122 serum samples from CHB patients from Yakutia and 211 serum samples from hepatitis delta patients from Yakutia (12 samples) and Tuva (199 samples) were collected. HBV serotypes/genotypes were determined by ELISA using developed reagents. The molecular methods included the isolation of HBV DNA, amplification of the S gene region (713 nt), and phylogenetic analysis of the nucleotide sequences. In a group of samples from CHB patients positive for HBV DNA (86 samples), 95% (82/86) valid results were obtained using our MAB kit. The following genotypes were identified: A, 32 (39%); C, 3 (4%); and D, 47 (57%). The results of HBV genotyping using two methods were identical for 81/82 (99%) samples. HBV genotyping using developed reagents provided 96.2% (203/211) of valid results in samples from patients with hepatitis delta compared to 3.8% of such results obtained using the standard molecular technic ( p < 0.001). The following HBV genotypes were identified: A, 17 samples (8.4%), and D, 186 samples (91.6%). The developed test with MAB panel allows one to reliably determine HBV genotype and has advantages over standard molecular methods for HBV genotyping in patients with hepatitis delta.

Abstract Background The geographic distribution of the hepatitis B virus (HBV) and the hepatitis D virus (HDV) genotypes is uneven. We reconstructed the temporal evolution of HBV and HDV in Yakutia, one of the regions of Russia most affected by HBV and HDV, in an attempt to understand the possible mechanisms that led to unusual for Russia pattern of viral genotypes and to identify current distribution trends. Methods HBV and HDV genotypes were determined in sera collected in 2018–2019 in Yakutia from randomly selected 140 patients with HBV monoinfection and 59 patients with HBV/HDV. Total 86 HBV and 88 HDV genomic sequences isolated in Yakutia between 1997 and 2019 were subjected to phylodynamic and philogeographic Bayesian analysis using BEAST v1.10.4 software package. Bayesian SkyGrid reconstruction and Birth–Death Skyline analysis were applied to estimate HBV and HDV population dynamics. Results Currently, HBV-A and HDV-D genotypes are prevalent in Yakutia, in both monoinfected and HDV-coinfected patients. Bayesian analysis has shown that the high prevalence of HBV-A in Yakutia, which is not typical for Russia, initially emerged after the genotype was introduced from Eastern Europe in the fifteenth century (around 600 (95% HPD: 50–715) years ago). The acute hepatitis B epidemics in the 1990s in Yakutia were largely associated with this particular genotype, as indicated by temporal changes in HBV-A population dynamics. HBV-D had a longer history in Yakutia and demonstrated stable population dynamics, indicating ongoing viral circulation despite vaccination. No correlation between HBV and HDV genotypes was observed for coinfected patients in Yakutia (r = − 0.016069332). HDV-2b circulates in Russia in Yakutia only and resulted from a single wave of introduction from Central Asia 135 years ago (95% HPD: 60–350 years), while HDV-1 strains resulted from multiple introductions from Europe, the Middle East, Central Asia, and different parts of Russia starting 180 years ago (95% HPD: 150–210 years) and continuing to the present day. The population dynamics of HDV-1 and HDV-2 show no signs of decline despite 20 years of HBV vaccination. The Birth–Death Skyline analysis showed an increase in the viral population in recent years for both HDV genotypes, indicating ongoing HDV epidemics. Conclusions Taken together, these data call for strict control of HBV vaccination quality and coverage, and implementation of HBV and HDV screening programs in Yakutia.

Hepatitis D (delta, δ) virus (HDV) was discovered more than 40 years ago, but the understanding of its origin and evolution is poor. This is mainly due to the lack, until recently, of data on the existence of any viruses similar to HDV. The discovery in recent years of sequences of new delta-like agents in a wide range of vertebrate (Vertebrata) and invertebrate (Invertebrata) species has facilitated a revision of views on the origin of HDV and contributed to understanding the place of this unique virus among other animals' viral agents. The purpose of this review is to analyze the latest published data on new delta-like agents and their biological characteristics.

INTRODUCTION:Hepatitis D (delta, 5) is caused by an RNA virus (hepatitis D virus, HDV) from genus Deltavirus, and is the most severe and difficult to treat disease among both viral hepatitis and infectious diseases in general. The development of HDV infection in the host organism is possible only in the presence of hepatitis B virus (HBV). Coinfection with HBV and HDV is associated with a more rapid progression of chronic viral hepatitis (CVH) to liver cirrhosis (LC) and an unfavorable outcome in comparison with HBV monoinfection. Data on the influence of clinical, biochemical and virological factors on the infectious process in patients with hepatitis D are limited due to the insufficient amount of research on this theme.The study aimed to determine demographic, clinical, biochemical, and virological factors influencing the course and progression of CVH D in patients followed during 10 years, residing in the territory of the Tuva Republic, one of the endemic regions of the Russian Federation.MATERIAL AND METHODS:Changes in clinical and laboratory parameters were analyzed in dynamics in 121 HDV infected patients with a different course of the disease, who were under observation from 2009 to 2019. Three groups of patients were identified: group 1 - 61 patients with disease progression of chronic hepatitis to LC (Child-Pugh class B-C), group 2 - 49 patients with non-progressive chronic hepatitis, and group 3 - 11 patients with slowly progressive LC (class A). Demographic data, the presence of detectable HBV DNA, indicators of the functional state of the liver: alanine aminotransferase (ALT/GPT), aspartate aminotransferase (AST/GOT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), and total bilirubin content were analyzed. The severity of hepatic encephalopathy was assessed by the duration of the numbers connection test (NCT).RESULTS:All patients belonged to the same ethnic group (Tuvinians), were infected with HDV genotype 1 and were positive for HDV RNA throughout the entire follow-up period. There were no significant differences in sex ratio and mean age at the time of inclusion in the study between the groups. In group 1, the average number of years from inclusion in the study to the formation of LC was 3.65 ± 2.3 years, years to the lethal outcome: 4.5 ± 3 years. Significantly higher levels of AST/GOT, ALP, GGT, total bilirubin (TB) and NCT grade were found in group 1 compared to group 2. ALT/GPT levels did not differ significantly in these groups. When comparing groups with disease progression and slowly progressive LC (groups 1 and 3), no significant differences were found in any of the clinical and biochemical parameters. ALT/GPT, GGT, TB and NCT values were significantly higher in patients with slowly progressive LC (group 3) compared to group 2. No differences in AST/GOT and ALP levels were found between these groups. Detectable HBV DNA was significantly more frequent in patients with progressive disease and with chronic viral hepatitis than in patients with slowly progressive LC. There were no significant differences in the frequency of HBV DNA detection in patients from groups 1 and 2.CONCLUSION:The results obtained on a relatively homogeneous cohort demonstrated that age and gender are not the factors influencing the progression of chronic viral hepatitis D to cirrhosis. The lack of detectable HBV DNA is associated with the slow progression of LC. The revealed differences in clinical and biochemical parameters reflect the degree of functional liver damage in chronic viral hepatitis D and HDV-associated cirrhosis.

Universal hepatitis B vaccination of newborns was implemented in Russia starting from 1998. From 1998 to 2019, the incidence of acute hepatitis B reduced from 43.8 to 0.57 cases per 100,000 population. Here, we assessed the timely coverage of newborns with the birth dose (HepB-BD), second dose (HepB-2nd), and three vaccine doses (HepB3) in two remote regions of Russia with low (Belgorod Oblast) and high (Yakutia) levels of hepatitis B virus (HBV) endemicity. Vaccination data were obtained from the medical records of 1000 children in Yakutia and 2182 children in Belgorod Oblast. Sera of healthy volunteers from Belgorod Oblast (n = 1754) and Yakutia (n = 1072) across all age groups were tested for serological markers of HBV to assess the infection prevalence and herd immunity. Average HepB-BD coverage was 99.2% in Yakutia and 89.4% in Belgorod Oblast (p < 0.0001) and in both regions varied significantly, from 66% to 100%, between medical centers. The principal reason for the absence of HepB-BD was parent refusal, which accounted for 63.5% of cases of non-vaccination (83/123). While timely HepB-2nd coverage was only 55.4%–64.7%: HepB3 coverage by the age of one year exceeded 90% in both study regions. HBV surface antigen (HBsAg) prevalence in the 1998–2019 birth cohort was 0.2% (95% CI: 0.01–1.3%) in Belgorod Oblast and 3.2% (95% CI: 1.9–5.2%) in Yakutia. The proportion of persons testing negative for both antibodies to HBsAg (anti-HBs) and antibodies to HBV core antigen (anti-HBc) in the 1998–2019 birth cohort was 26.2% (125/481) in Belgorod Oblast and 32.3% (162/501) in Yakutia. We also assessed the knowledge of and attitude towards vaccination among 782 students and teachers of both medical and non-medical specialties from Belgorod State University. Only 60% of medical students knew that hepatitis B is a vaccine-preventable disease. Both medical and nonmedical students, 37.8% and 31.3%, respectively, expressed concerns about safety and actual necessity of vaccination. These data indicate the need to introduce a vaccine delivery audit system, improve medical education with respect to vaccination strategies and policies, and reinforce public knowledge on the benefits of vaccination.