Vera S. Kichatova

Introduction. The Amur Region (AR) is a territory with developed pig farming and traditional reindeer herding, which creates potential risks for transmission of hepatitis E virus (HEV) zoonotic genotypes. The aim of the study was to conduct a comparative analysis of anti-HEV antibody prevalence among AR residents with different levels of zoonotic risk of HEV infection (living in areas with developed pig farming and traditional reindeer herding), as well as among pig and reindeer (Rangifer tarandus) populations. Materials and methods. A total of 1114 serum samples from conditionally healthy volunteers of three groups were tested for anti-HEV antibodies using ELISA: residents of settlement No. 1 at the pig-breeding complex (n = 90), residents of settlement No. 2 engaged in traditional reindeer herding (n = 102), and residents of other areas of the AR (n = 922). Blood sera from pigs (n = 197) and reindeer (n = 97) were also tested for anti-HEV antibodies in ELISA with a species-specific conjugate. HEV RNA detection was performed in the reindeer blood sera and swine fecal samples using nested PCR and real-time PCR. Risk factors were assessed using the binary logistic regression method. Results. Anti-HEV IgG antibody detection rate among residents of Settlement No. 1 was 14.4%, significantly higher compared to residents of Settlement No. 2 (3.9%) and other regions of the AR (3.8%). The independent predictors of HEV seropositivity were residence in Settlement No. 1 (OR = 6.32) and age (OR = 1.06). The detection rates of anti-HEV IgG antibody were 96.4% among pigs and 92.8% among reindeer. Despite the high seroprevalence among reindeer, reindeer herders and their family members were not a risk group for HEV infection (OR = 0.8). No HEV RNA was detected in animal samples. Conclusion. The HEV seroprevalence rate detected among the population of the AR corresponds to the Russian average level. Pig farm workers and their family members are at increased risk of HEV infection, which justifies the need to develop preventive measures for this group. The high seroprevalence among reindeer requires further molecular research to clarify their role as a zoonotic reservoir of HEV infection.

Introduction. Genetic monitoring of hepatitis A virus (HAV) is an important tool for surveillance of this infection and the identification of hepatitis A outbreaks. The aim of the study was to analyze the genetic diversity of HAV variants involved in sporadic and cluster cases of hepatitis A in 2022–2025. Materials and methods. A total of 402 HAV VP1/2A partial sequences isolated from sporadic and cluster cases in 2022–2025 in various regions of the Russian Federation were analyzed. Phylogenetic trees were constructed using a Bayesian approach implemented in the Beast2 software package using HAV sequences isolated in regions of the Russian Federation and neighboring countries since 1998. To assess changes in genetic diversity, p-distance values were analyzed in four HAV sequence samples, divided based on virus genotype and the year the sequences were isolated — before or after 2020. Results. The persistent circulation of two HAV genotypes, IA and IIIA, was demonstrated. The share of genotype IA was 78.4%, genotype IIIA — 12.7%, and imported genotype IB — 8.9%. Both genotypes, IA and IIIA, contribute to both sporadic and outbreak cases. 98% of HAV genotype IA isolates belonged to a single lineage originating from the strain that caused the 2010 outbreak in Moscow. Analysis of p-distance values confirmed a decrease in HAV genetic diversity — for genotype IA before 2020, this indicator ranged from 0.000 to 0.316, and from 0.000 to 0.087 in 2020–2024. For genotype IIIA, a decrease in the p-distance indicator was also noted, from 0.000–0.080 before 2020 to 0.000–0.029 in 2020–2024. Conclusion. The obtained results indicate a decrease in the genetic diversity of HAV against the background of a decrease in hepatitis A incidence rates, and suggest that analysis of longer regions of the viral genome might be required for molecular surveillance and outbreak investigation in the future, if the trend of decreasing genetic diversity of the virus remain.

The aim of this study was to conduct an epidemiological analysis of hepatitis C infection in children with oncohematological diseases (OHD) using phylogenetic analysis of HCV nucleotide sequences and to analyze the causes and factors of HCV nosocomial transmission. Materials and methods. A retrospective analysis of HCV genetic isolates obtained from children with oncohematological diseases treated at the «Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology» (the Center) was conducted. The analysis included all children with HCV markers (anti-HCV and/or HCV RNA) identified between 2013 and 2025 during hospitalization and treatment at the Center—a total of 146 children. The children's ages ranged from 0 to 18 years, and from September 1, 2022, to 21 years. Samples were taken from the Center's bacteriology laboratory collection. Genotyping and phylogenetic analysis were performed at the Central Research Institute of Epidemiology of Rospotrebnadzor for 30 patient blood samples containing HCV RNA in quantities sufficient for analysis (at least 1000 IU/mL). To compare the distribution of HCV genotypes, the VGARus database data from 997 individuals was used. The core/E1 region of the HCV genome was sequenced and a phylogenetic analysis was performed. A Bayesian approach was used with the BEAST2 software package. The tree was visualized using FigTree. Results. In the structure of HCV genotypes isolated from children in the oncohematology departments, genotype 3a was predominant (77%), while 1b accounted for 23%. In contrast to the general population, where genotypes 3a and 1b circulate with equal frequency, the prevalence of genotype 3a among children with OHD indicates a greater involvement of this genotype in cases of nosocomial infection. Phylogenetic analysis revealed three common HCV clusters: 14 children with genotype 3a (13 children from the Amur Region and 1 child from the Altai Krai) and two common clusters with genotype 1b (2 patients each from the Kyrgyz Republic and Uzbekistan). The majority of HCV infection cases in children with OHD (60%) were nosocomial in origin. Cases of HCV infection in children from the Amur Region are associated with a long-standing chronic HCV epidemic in the oncohematology department of the Amur Regional Children's Clinical Hospital. No cases of infection have been identified at the Center. A patient from the Altai Krai region may have been infected at the Center in 2013-2014 during blood collection from a central venous catheter (CVC) due to improper hand sanitization, glove changing, aseptic technique, or work surface zoning. Standardization of procedures, implementation of aseptic non-touch technique (ANTT), training, and monitoring of staff knowledge and skills, widely implemented in the Center's work, have demonstrated high effectiveness, resulting in the absence of HCV transmission cases for over 10 years. Conclusion. Nosocomial HCV transmission in the OHD departments requires the widespread implementation of modern approaches to preventive and anti-epidemic measures, such as aseptic non-touch technique (ANTT), standardization of procedures, staff training, and knowledge and skills audits.

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.

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.

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 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.

Introduction. Although domestic pigs and wild boars are the main reservoir of zoonotic hepatitis E virus (HEV) genotypes in temperate countries, the presence of antibodies to HEV (anti-HEV) in the indigenous population of circumpolar territories, i.e. outside the habitat of wild and domestic pigs, indicates the presence of an alternative reservoir of the virus. Reindeer (Rangifer tarandus) may be a potential reservoir for HEV in the polar regions. The purpose of the study was to determine the prevalence of anti-HEV among domestic reindeer in the Republic of Sakha (Yakutia). Materials and methods. Sera from 497 domestic reindeer from the Oymyakon (n = 425) and Ust-Yansky districts (n = 72) of the Republic of Sakha (Yakutia) were tested for anti-HEV. A commercial ELISA kit DS-ELISA-ANTI-HEV-G (Diagnostic Systems-Stolitsa LLC, Russia) was used for detection of anti-HEV IgG, but a rabbit polyclonal antibody against deer IgG labeled with horseradish peroxidase (KPL, USA) at a dilution of 1 : 100 in phosphate-buffered saline were used instead of the human specific conjugate from the kit. Results. The average detection rate of anti-HEV in reindeer sera was 15.5% (95% CI: 12.6–19.0%). The detection rate of anti-HEV significantly increased with age, from 3.5% (95% CI: 1.1–9.0%) in calves aged 3–6 months to 25.0% (95% CI: 1.6 –36.5%) in deer aged 2–4 years (p 0.0001). From this age group, anti-HEV detection rates reached a plateau, not differing significantly between older age groups (p 0.05). The average anti-HEV detection rate among reindeer 2 years of age and older was 19.0% (95% CI: 15.3–23.4%). There were no statistically significant differences in the frequency of anti-HEV detection between female and male reindeer, both among adult animals and among calves. Conclusion. The observed anti-HEV detection rates among domestic reindeer in the Republic of Sakha (Yakutia) indicate that infection caused by HEV or an antigenically similar virus is common in these animals. The dynamics of antibody accumulation in the reindeer population indicates that infection apparently occurs during the first two years of life.

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.

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.