Mikhail I. Mikhailov

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.

Background. Hepatitis E virus (HEV) remains a significant concern for the public health system of the Republic of Belarus due to the widespread circulation of zoonotic genotype 3 among the population and animals. Objective. To evaluate clinical and laboratory features and identify prognostic markers of the course of acute hepatitis E in hospitalized adult patients in Minsk. Material and methods. We conducted a retrospective analysis of 51 medical records of patients with a verified diagnosis of acute hepatitis E (IgM anti-HEV (+) and/or PCR (+)) treated in infectious disease hospitals in Minsk between 2016 and 2026. Clinical presentation, severity, length of stay, as well as biochemical parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase (ALP), gammaglutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), ferritin, C-reactive protein (CRP), urea, creatinine) were assessed. Statistical processing was performed using nonparametric methods (Mann–Whitney U test, Kruskal–Wallis H test, Spearman's rank correlation coefficient). Differences were considered statistically significant at p<0.05. Results. The icteric form was diagnosed in 78.4% (n=40) of patients and was characterized by significantly higher levels of ALT (p=0.002), AST (p=0.001), bilirubin (p<0.001), ALP (p=0.008), and GGT (p=0.003). Disease severity correlated most strongly with total bilirubin (ρ=0.63; p<0.001) and AST (ρ=0.51; p<0.001) levels. Length of stay depended on bilirubin (ρ=0.45; p=0.002) and urea levels (ρ=0.51; p=0.003). Ferritin levels were significantly higher in patients with a severe form of the disease (ρ=0.60; p=0.02). Conclusion. Hepatitis E in Minsk is characterized by a predominance of icteric forms with a pronounced cholestatic component. Total bilirubin and urea levels can be considered feasible prognostic markers for length of stay.

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.

Objective . To determine the specificity and sensitivity of the developed domestic enzyme-linked immunosorbent assay kit “ELISA-anti-HEV IgM” for detecting M class immunoglobulins to the hepatitis E virus (HEV) in human serum under real clinical conditions. Materials and methods . To determine the sensitivity and specificity, we used registered industrial samples of the “ELISA-anti-HEV IgM” kit, produced by Unitary Enterprise “Pilot Production of the Institute of Bioorganic Chemistry National Academy of Sciences of Belarus” in accordance with TU BY 100185093.093-2023. 214 blood serum samples from patients with established presence of antibodies to hepatitis A virus, hepatitis C virus, hepatitis B virus antigen, hyperlipidemia, class M antibodies to cytomegalovirus and increased content of rheumatoid factor were examined on the basis of the clinical and diagnostic laboratory of the healthcare institution “City Clinical Infectious Diseases Hospital” of Minsk. To determine the sensitivity and specificity of the set, 72 serum samples were examined in parallel with reference sets “Vecto gep E-IgM”. Results . When using the industrially released “ELISA-anti-HEV IgM” (TU BY 100185093.093-2023), the absence of non-specific cross-interaction between the sorbed recombinant polypeptides ORF2 and ORF3 of hepatitis E virus genotype 3 and proteins in samples of patients with antibodies to hepatitis C, hepatitis A, hepatitis B virus antigen, blood plasma with hemolysis and chylosis, samples with an increased content of rheumatoid factor and the presence of class M antibodies to cytomegalovirus. When evaluating sensitivity and specificity indicators on blood sera under real clinical conditions, high sensitivity indicators were established – at least 99% and specificity – at least 99%, which indicates the possibility of using the kit in the practical activities of laboratories of healthcare institutions. Conclusion . The registered and manufactured first domestic test system for the determination of class M immunoglobulins against hepatitis E virus (HЕV) in human blood serum “ELISA-anti-HEV IgM” by indirect enzyme immunoassay has high analytical reliability: sensitivity is at least 99%, specificity is at least 99%,

Introduction. Kyrgyzstan, among other Central Asian countries, is one of the highly endemic regions for hepatitis A. An important tool for assessing the true burden of these infections on the population and the success of ongoing prevention programs is to study the prevalence of markers of past and current hepatitis A in all age groups of the population, as well as the intensity of population immunity to this virus in regions with different morbidity. Aim. To study the hepatitis A virus (HAV) seroprevalence among residents of the Kyrgyzstan regions. Materials and methods. Blood serum samples from conditionally healthy individuals (n = 2297) who sought medical attention at medical institutions in Bishkek, Batken, Chüy, Jalal-Abad, Issyk-Kul, Osh, Talas and Naryn regions. IgM and IgG antibodies to hepatitis A virus (anti-HAV IgM, anti-HAV IgG) were determined using the «Vectohep A-IgM» and «Vectohep A-IgG» (Vector-Best) enzyme immunoassay kits. Statistical processing of the results was carried out using Excel and Medcalc programs. Results. 80.3% of the studied samples contained HAV serologic markers, of which 80.3% contained anti-HAV IgG antibodies and 4.7% contained anti-HAV IgM antibodies. All IgM-positive samples contained specific IgG antibodies. Such samples were identified with the same frequency among women and men. The highest seropositivity rates were observed in the age groups 30–39, 40–49, and 50–59 years. The number of individuals with anti-HAV IgG antibodies in their blood serum increased with their age. An analysis of the immunostructure of the examined individuals by the level of anti-HAV IgG in serum showed relatively stable ratios of low, medium and high levels of antibodies in groups older than 30 years. The most frequently anti-HAV IgM and IgG antibodies were detected in samples from residents of Bishkek. Anti-HAV IgG antibodies were detected in samples from all surveyed regions of Kyrgyzstan, while anti-HAV IgM antibodies were identified in samples from Chüy, Issyk-Kul and Osh regions, as well as Bishkek. Conclusion. Hepatitis A remains widespread in Kyrgyzstan. The determination of HAV seromarkers in the algorithms of complex hepatitis diagnostics and seroepidemiological studies remains relevant. A decrease in the level of population immunity to HAV in younger age group indicates the country's transition from high to medium endemicity, which suggests an increase in the number of clinically pronounced cases in the future in the absence of a hepatitis A vaccination program for children.

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.

Hepatitis A is an acute liver disease caused by the hepatitis A virus (HAV), which can be prevented by means of vaccination. The standard hepatitis A vaccination schedule consists of two doses of inactivated vaccine, but for economic reasons and the purpose of improving vaccination coverage, universal pediatric single-dose vaccination programs have been implemented in certain regions of the world. The aim of this review is to summarize and analyze published data on the duration of protective antibody levels after a single-dose pediatric immunization, as well as hepatitis A incidence in countries where hepatitis A vaccination is carried out using a single dose of inactivated vaccine. Recent data from different regions of the world, including the Russian Federation, support the effectiveness of the single-dose hepatitis A vaccination strategy, both in terms of the duration of the immune response and the impact on the incidence rates. However, further studies on the long-term effectiveness of single-dose immunization with inactivated vaccine, as well as continuous hepatitis A surveillance, are necessary to assess the duration of protection and the necessity for booster vaccination later in life

Introduction: Hepatitis A is typically a benign disease; however, in rare instances, it can progress to a fulminant course. One uncommon complication of this disease is acute kidney injury (AKI), which requires clinicians’ awareness for timely diagnosis and treatment. Case Presentation: We describe a clinical case involving a 34-year-old man with severe hepatitis A, who had no comorbid conditions. His condition was complicated by acute hepatic encephalopathy of the first stage and AKI. Notably, there were no provoking factors contributing to the development of AKI. This case underscores the importance of recognizing and treating atypical manifestations of acute hepatitis A promptly. Conclusions: This clinical case highlights the significance of a differential diagnostic approach when AKI emerges as the leading clinical syndrome. It also indicates the need for increased awareness among relevant specialists regarding atypical presentations of acute hepatitis A.