Clinical Practice Guidelines of the Russian Society for the Study of the Liver, the Russian Gastroenterological Association, the National Scientific Society of Infectious Disease Specialists for the Diagnosis and Treatment of Chronic Hepatitis C

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

РАСПРОСТРАНЕННОСТЬ ВИРУСА ГЕПАТИТА С СРЕДИ УСЛОВНО ЗДОРОВОГО НАСЕЛЕНИЯ РОССИЙСКОЙ ФЕДЕРАЦИИ

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. Цель. Определить долю инфицированных вирусом гепатита С (ВГС) лиц в различных возрастных группах условно здорового населения России.Материалы и методы. Исследованы 4764 образца сы- воротки крови от условно здорового населения пяти регионов РФ: Свердловской, Ростовской, Московской областей, Республики Тыва и Республики Саха (Якутия). В исследование были включены лица 10 возрастных групп: меньше 1 года, 1–4 года, 5–9 лет, 10–14 лет, 15–19 лет, 20–29 лет, 30–39 лет, 40–49 лет, 50–59 лет, старше 60 лет. Анти-ВГС определяли в ИФА с коммерческими тест-системами. В положительных по анти-ВГС образцах определяли РНК ВГС методом ОТ-ПЦР. Генотип ВГС определяли на основании анализа нуклеотидных последовательностей участков core и NS5B вирусного генома.Результаты. Общая распространенность анти-ВГС в 5 регионах РФ составила 2,6% (126/4764), доля лиц с РНК ВГС – 1,1% (50/4764). Наибольшая распространенность анти-ВГС выявлена в Республиках Тыва и Якутия (3,3%), в остальных регионах данный показатель варьировал от 1,7% (Московская область) до 3,0% (Свердловская область). Наибольшая частота выявления РНК ВГС отмечена в Республике Тыва и Ростовской области (1,3% в обоих регионах). Среди лиц в возрасте от 0 до 19 лет РНК ВГС не была выявлена ни в одном регионе, за исключением Республики Тыва (1% (1/98) в группе 15–19 лет). Пиковые показатели выявления РНК ВГС были вы- явлены в возрастных группах 20–29 лет и 30–39 лет в Ростовской области (3,9% и 3,0% соответственно); в Якутии – в группе 30–39 лет (3,7%), в Тыве – в группе 40–49 лет (3,6%), в Московской области – в группах 20–29 лет и 30–39 лет (2,9% и 2,5% соответственно).Заключение. Полученные результаты свидетельствуют о высокой степени пораженности ВГС практически всех возрастных групп в интервале от 20 лет до ≥ 60 лет. В каждом из обследованных регионов выявлены возрастные когорты, для которых целесообразно включение в региональные скрининговые программы.

BALAYAN PARADOX

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

FREQUENCY OF DETECTION OF ANTIBODIES TO HEPATITIS C VIRUS AMONG CONVENTIONALLY HEALTHY POPULATION OF RUSSIAN FEDERATION

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

The prevalence of the hepatitis C virus among the conditionally healthy population of the Russian Federation

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

DESIGN OF HEPATITIS E VIRUS GENOTYPE 1 RECOMBINANT ORF3 PROTEIN BY CODON OPTIMIZATION METHOD

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