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Аim: diagnosis and treatment algorithms in the clinical recommendations intended for general practitioners, gastroenterologists, infectious disease specialists, hepatologists on the of chronic hepatitis C are presented.Summary. Chronic viral hepatitis C is a socially significant infection, the incidence of which in the Russian Federation remains significantly high. Over the past 10 years, great progress has been made in the treatment of hepatitis C — direct acting antiviral drugs have appeared. The spectrum of their effectiveness allows to achieve a sustained virological response in more than 90 % of cases, even in groups that were not previously considered even as candidates for therapy or were difficult to treat — patients receiving renal replacement therapy, after liver transplantation (or other organs), at the stage of decompensated liver cirrhosis, HIV co-infected, etc. Interferons are excluded from the recommendations due to their low effectiveness and a wide range of adverse events. The indications for the treatment have been expanded, namely, the fact of confirmation of viral replication. The terms of dispensary observation of patients without cirrhosis of the liver have been reduced (up to 12 weeks after the end of therapy). Also, these recommendations present approaches to active screening of hepatitis in risk groups, preventive and rehabilitation measures after the end of treatment.Conclusion. Great success has been achieved in the treatment of chronic hepatitis C. In most cases, eradication of viral HCV infection is a real task even in patients at the stage of cirrhosis of the liver, with impaired renal function, HIV co-infection, after solid organs transplantation.

2021 marks the 40th anniversary of the discovery of the hepatitis E virus by an outstanding Russian virologist, academician of the Russian Academy of Medical Sciences Mikhail Surenovich Balayan. This date is an occasion to remember this remarkable scientist and person, to analyze the current state of the problem of viral hepatitis E, to sum up the research results and to correct the prospects of scientific directions, the development of which is largely related to the basic foundations laid by M.S. Balayan.The scientific heritage of M.S. Balayan is associated with the study of poliomyelitis, hepatitis A and hepatitis E. The main contribution of Mikhail Surenovich Balayan to world science was the discovery of the hepatitis E virus. This is, in first place, associated with the significance of the results obtained and the high moral value of the experimental selfinfection with hepatitis E.The paper presents data on the study of virology, epidemiology, clinical course, diagnosis and prevention of hepatitis E. The main concepts and directions of studying hepatitis E are overviewed.

Introduction. Belgorod region is the territory with the highest incidence of hepatitis E in the Russian Federation. The aim of the study was to comprehensively characterize the circulation of hepatitis E virus (HEV) in the Belgorod region, including the study of population immunity to the virus, determining the prevalence of infection among the pig population and analysis of the genetic diversity of HEV from patients and animals. Material and methods. Serum samples of a conditionally healthy population (n = 2027) of all age groups were tested for anti-HEV IgG and IgM by ELISA with commercial assays. HEV RNA was determined in fecal samples from pigs aged 2–4 months (n = 526), in sewage samples from pig farms (n = 10), as well as in stool samples from patients with hepatitis E (n = 6) using reverse transcription polymerase chain reaction (RT-PCR). Phylogenetic analysis was performed for an amplified 300 nt fragment corresponding to HEV open reading frame 2. Results and discussion. The prevalence of anti-HEV IgG in general population averaged 16.4% (95% CI: 14.8–18.1; 332/2027). The proportion of individuals who had both anti-HEV IgM and IgG averaged 2.8% (95% CI: 2.2–3.6; 57/2027). The incidence rate of anti-HEV IgG increased with age, from 2.8% (95% CI: 1.3-5.8) in children aged 1–14 years to 40.1% (95% CI: 34.9-45.6) in people 70 years or older. The detection rate of HEV RNA in pigs was 20% (95% CI: 16.8-23.6; 105/526). HEV RNA was detected in 2 out of 10 sewage samples. The HEV sequences isolated from patients with hepatitis E, pigs, and sewage samples in Belgorod region belonged to the HEV genotype 3, had a 95-100% homology, and formed common clusters on a phylogenetic tree. Conclusions. The high prevalence of HEV in pigs population has led to the formation of an endemic territory in the Belgorod region, which is the center of pig breeding. Measures aimed at reducing the circulation of HEV among pig population and decontamination of sewage from pig farms are necessary to control HEV infection.

Aim. The development of the hepatitis E virus (HEV) genotype 3 recombinant capsid protein. Materials and methods. E.coli strains, plasmid vectors, serological and clinical samples, ELISA reagent kits, molecular biological, bioinformatic, biotechnological, biochemical and serological methods. Results. Using viruscontaining material from pigs of Belgorod region (Russian Federation) we made E.coli strains producing recombinant capsid protein, containing C-terminal of viral ORF2 protein fragment fused to E.coli β-galactosidase. Recombinant protein ORF2 had been isolated from the bacterial inclusion bodies and purified by size exclusion chromatography. Antigenic specificity of the recombinant polypeptide was confirmed by ELISA and Western blotting with sera of hepatitis E patients and reference groups (healthy donors, patients with hepatitis A, B, C, infectious mononucleosis, cytomegalovirus infection and HIV-infected patients). Conclusion. HEV genotype 3 ORF2 recombinant antigen had been developed, and the possibility to use it in diagnostic tests had been experimentally shown.

This article presents the results of a study of the epidemiology of hepatitis E in the Russian Federation. Obtained data explaining the phenomenon, known as the Balayan paradox — the wide distribution of anamnestic antibodies to the hepatitis E virus in the absence of a registered incidence. It was shown that imported cases of infection are not able to support the epidemiological process of hepatitis E in Russia. The most cases of HEV infection are autochthonous in nature and are associated with zoonotic transmission of genotype 3 virus from pigs.

Aim. To determine the prevalence of amino acid substitutions in hepatitis C virus NS5a and core proteins which are associated with resistance to direct-acting antivirals and interferon in genotype 1b (HCV-1b) strains circulating in Russia. Materials and methods. Nucleotide sequences of NS5a (n=93) and core (n=30) of HCV-1b were obtained using direct sequencing of respective amplified genome fragments. The search for resistance associated substitutions was performed for amino acid positions 28, 29, 30, 31, 32, 58, 62, 92, 93 of NS5a, and 70 and 91 amino acid positions of core proteins, respectively. Results. The total proportion of HCV-1b strains carrying resistance associated substitutions in NS5a was 22,6% (21/93). The total detection rate of L31M and Y93H substitutions that are associated with resistance to the majority of NS5a inhibitors was 10,8%. Less clinically significant substitutions L28M, R30Q, P58S/T, A92T were detected too. The proportion of infections caused by HCV-1b strains that are potentially resistant both to interferon and NS5a inhibitors was 10% (10/30). Conclusion. Testing of HCV-1b infected patients for background resistance profile could be a useful tool to prevent the choosing of initially ineffective treatment regimen.

Researches of parenteral viral hepatitis prevalence in Republic of Sakha (Yakutia) showed high frequency of hepatitis B and C infection markers. High level of HBsAg carriage among indigenous nationalities representatives living in isolated ethnic group had been revealed (12,9%). HBsAg and anti-HBc detection frequencies is 12,9% and 76,0% respectively in comparison with 5,8% and 14,6% among newcomer population (p

Aim. The development of the hepatitis E virus (HEV) genotype 1 full-size ORF3 recombinant polypeptide. Materials and methods. Escherichia coli strains, plasmid vectors, serological and clinical samples, ELISA reagent kits, molecular biological, bioinformatic, biotechnological, biochemical and serological methods. Results. HEV genotype 1 RNA had been isolated from clinical samples collected in Kyrgyzstan. DNA copy of subgenomic virus RNA had been cloned and used for further development of E.coli strains producing full-size recombinant protein ORF3 fused to E.coli beta-galactosidase. Codons optimization method was used in aim to increase expression level of recombinant protein. Recombinant protein ORF3 had been isolated from the inclusion bodies of the E.coli biomass and purified by size exclusion chromatography. Antigenic specificity of recombinant polypeptide had been confirmed by enzyme-linked immunosorbent assay and Western blotting with the specific sera. Conclusion. HEVgenotype 1 ORF3 recombinant antigen had been designed, and it’s applicability in diagnostic tests had been experimentally confirmed.

Aim. Determine the prevalence of antibodies to hepatitis C virus (anti-HCV) among conditionally healthy population of Russian Federation. Materials and methods. Sera samples obtained from conditionally healthy population of the Russian Federation from 5 geographically distant regions with different levels of morbidity for hepatitis C were studied: Sverdlovsk, Rostov, Moscow regions, Tyva and Sakha (Yakutia) Republics. 4764 samples were studied in total obtained from individuals of 10 age groups: younger than 1, 1 - 4, 5 - 9, 10 - 14,15 - 19, 20 - 29, 30 - 39, 40 - 49,50 - 59, olderthan 60 years. Anti-HCV were determined by commercial ELISA. Results. The total prevalence of anti-HCV in 5 regions of Russian Federation was 2.6% (126/4764). The highest frequency of detection of anti-HCV was detected in Tyva and Yakutia Republics and was 3.3%, in other regions this parameter varied from 1,7 (Moscow region) to 3% in Sverdlovsk region. Peak parameters of anti-HCV detection among population in various regions were connected with various age groups: olderthan 60 years in Tyva and Yakutia Republics (11 and 9.9%, respectively), 40 - 49 in Moscow region (6.2%), 1 - 4 and 30 - 39 years in Sverdlovsk region (5.9 and 4.9%, respectively) and 20 - 39 in Rostov region (3.9%). Conclusion. Results of anti-HCV detection in various age cohorts of conditionally healthy population of Russian Federation give evidence regarding high morbidity with HCV of almost all the age groups in the interval from 20 to older than 60 years. Age cohorts were detected in each of the studied regions for which inclusion into regional screening programs is feasible.

Aim. To determine the prevalence of hepatitis C virus (HCV) in different age groups of the conditionally healthy population of Russia.Materials and methods. Total 4764 serum samples from a conditionally healthy population of five regions of Russia (Moscow, Rostov, Sverdlovsk regions, Tyva Republic, and Sakha Republic (Yakutia) were tested. The study included persons of 10 age groups: < 1 year, 1–4 years, 5–9 years, 10–14 years, 15–19 years, 20–29 years, 30–39 years, 40–49 years, 50–59 years old, ≥ 60 years. Anti-HCV was determined in ELISA with commercial test systems. Anti-HCV positive samples were tested for HCV RNA by RT-PCR. The genotype of HCV was determined based on the analysis of the nucleotide sequences of the core and NS5B regions of the viral genome.Results. The overall prevalence of anti-HCV in 5 regions of Russia was 2,6% (126/4764), and the proportion of people with HCV RNA was 1,1% (50/4764). The highest anti-HCV positivity rate was observed in Tyva and Yakutia (3,3% in both regions), in other regions its prevalence varied from 1,7% (Moscow region) to 3,0% (Sverdlovsk region). The highest frequency of HCV RNA detection was observerd in Tyva Republic and Rostov region (1.3% in both regions). No positive for HCV RNA cases was detected among persons aged 0–19 years in any region, except for Tyva Republic (1,0% (1/98) in age group 15–19 years). Peak positivity rates of HCV RNA were detected in the age groups 20–29 years and 30–39 years in the Rostov Region (3,9% and 3,0%, respectively); in Yakutia – in the group of 30–39 years (3,7%), in Tyva – in the group of 40–49 years (3,6%), in the Moscow region – in the groups of 20–29 and 30–39 years (2,9% and 2,5%, respectively).Conclusion. The results obtained indicate a high degree of HCV infection in virtually all age groups in the interval from 20 years to ≥60 years. Specific age cohorts that might benefit from inclusion in regional HCV screening programs were identified in each region.

Aim. Description of the first documented case of imported hepatitis E, associated with genotype 4 of HEV and introduced from southern France. Materials and methods. Clinical, epidemiologic and laboratory analysis of the imported case of disease of hepatitis E was carried out. Phylogenetic analysis of nucleotide sequences of HEV isolate, taken from the patient, was carried out. Results. Epidemiologic analysis allowed to assume imported character of the detected case of HEV-infection. Comparative analysis of nucleotide sequences of regions of the open reading frame 2 (300 nt) and open reading frame 1 (721 nt) of HEV genome, isolated from the patient, showed identity of this isolate with variants of genotype 4 HEV, isolated in France in 2009 - 2011 from patients with autochthonous hepatitis E. Conclusion. The results obtained confirm the case of import into Russia of genotype 4 HEV from south-eastern France (Corsica), where spread of this virus genotype is observed in recent years.

The records of total 123 patients with hepatitis E on treatment in the infectious diseases hospital in the city of Belgorod were reviewed. Diagnosis – «acute hepatitis E» was based on the generally accepted criteria: biochemical analysis, etiological interpretation (identification of antibodies to hepatitis E of the IgM and IgG, HEV RNA with the exception of the etiologic role of other hepatotropic viruses, including Epstein-Barr virus and cytomegalovirus). HEV RNA was determined by PCR, genotyping was performed by standard methods based on the results of sequencing. The study of clinical manifestations in patients with acute hepatitis E allowed to establish some specific features of hepatitis E: predominantly occurrence in adults at the age 30 years and more; frequent complaints of arthralgia in the prejaundice period, the lack of improvement after jaundice development; pronounced dyspeptic symptoms and long bilirubinemia combined with mild transaminase elevation, hepatomegaly with no concomitant increase in the spleen. The data on the fulminant forms of hepatitis E are presented. Herein we describe the case of fulminant course of infection with a fatal outcome. Analysis of cases of severe hepatitis E have revealed the following risk factors: heart disease, chronic biliary disease, obesity, diabetes mellitus, chronic alcohol intoxication. The analysis of specific clinical manifestations of this infection is needed to select the right strategy of patient following, to set integrated differential diagnostic approach in the management of patients with middle and old age with the presence of jaundice and patients with hepatitis of unknown etiology. The inclusion of hepatitis E markers to the diagnostic algorithm is necessary for such patients.

Abstract. The results of clinical and epidemiological studies conducted in the M.P. Chumakov’ Research Institute of Poliomyelitis and Viral Encephalitis and in the different research institutions of the world have been summarized in the current article. Data on etiology, pathogenesis, clinical symptoms, epidemiology and prevention of hepatitis E are presented. Increasing of significance of this infection for health care system in Russia is emphasized . The actual problems of hepatitis E (autochthonic hepatitis E, hepatitis E as zoonosis, chronic hepatitis E) are discussed.