Study aims: The study purpose was to analyze the results of the clinical and laboratory monitoring of HBeAg-negative chronic hepatitis B patients after discontinuation of longterm nucleosides analogues antiviral therapy in order to determine further management.Materials and methods: A retrospective-prospective investigation was performed in 106 patients with diagnosis of HBeAg-negative chronic hepatitis B during the course of antiviral therapy using nucleosides analogues. Average treatment duration was 190,1±77,7 weeks. The therapy was discontinued for 29 patients in the period of time from two to five years of the treatment, they were followed up from 6 months to 6 years. The activity of aminotransferases, the levels of HBV DNA were evaluated, the liver elastometry was performed during the patients monitoring. The relapse of disease after the treatment discontinuation was considered when the viral load exceeded 2.0x103 IU / ml and/or alanine aminotransferase levels were above the reference values.Results:The viral load varied from 4,0х102 IU/ml to 2,87 х 107 IU/ml at 86,2% cases after the 6 months of discontinuation of the treatment. However median levels of viral load were not higher than 2,5 х 103 IU/ml at different timepoints of observation. The VL was higher than 2,0 х 103 IU/ml in 62,1% patients and it matched to relapse criterion. Clinical relapse was not revealed in 13,8% cases at observational period from 6 months to 2 years. The second course of antiviral therapy was not required for 37,9% patients, at the same time it was necessary to consider it for the rest ones.Conclusion: Regular medical checkups with periodical clinical, laboratory and instrumental examinations after antiviral treatment discontinuation are required for timely detection of relapse and decision regarding the next course of antiviral therapy.

Rationale: Enteric hepatitis including hepatitis A and hepatitis E are globally prevalent diseases with large social and economic burden. In some patient categories these may be lethal. Hepatitis A (HAV) and hepatitis E (HEV) viruses are heterogeneous and have high geographic variability.Aim: To assess current epidemiological, molecular and genetic characteristics of enteric viral hepatitis in the Russian Federation.Materials and methods: We analyzed the data of the State statistical reports on the incidence of infectious diseases in the Russian Federation and of the analytical tables. Also, genotype identification of the HAVs isolated from 31 patients living in St. Petersburg was performed with specific primers flanking VP1/2A region.Results: In the last 20 years (from 1997 to 2017), the epidemic process of hepatitis A in the Russian Federation has been changing substantially, including first of all its intensity and age distribution of the patients. Unlike hepatitis A, the official registration of hepatitis E in the Russian Federation was initiated only in 2013. During the analyzed time period, the incidence of hepatitis E varied from 0.06 to 0.08⁰⁄₀₀₀₀, with non-significant trend towards its increase in 2017. It has been found that from 2013 to 2015, two sub-genotypes of the virus (1a and 1b) circulated in St. Petersburg, with prevailing genotype 1a. The local cases of hepatitis E were caused by HEV genotype 3, whereas the imported cases, by HEV genotype 1.Conclusion: In the Russian Federation, there has been a long-standing and stable trend toward decreased incidence of hepatitis A. However this has led to weakening of collective immunity, mainly among the adult population. In combination with poor levels of municipal infrastructures and services in some territories, this may lead to an increase of the hepatitis A incidence. Despite that Russia is a non-endemic region for hepatitis E, local cases of the disease are increasingly identified.

Currently, second-generation hepatitis B vaccines are widely used. They are produced in biotechnological eukaryotic yeast-based systems and contain the S-protein domain of HBsAg particle in the complete absence of pre-S1 and pre-S2 domains. At the same time, these antigens were proved to significantly influence immunogenicity, which makes the development and use of third-generation vaccines containing all antigenic determinants a long-range objective. A randomized, double-blind clinical study was conducted to compare immunogenicity of second- and third-generation vaccines Engerix-B™ and Sci-B-Vac™, respectively. Healthy subjects of both sexes aged 18 to 45 years (n = 94) who are seronegative for HBsAg, HBsAb, HBcAb at screening and who previously had not received immunobiological agents for hepatitis B prophylaxis were included in the study. Group I (n = 47) received the second-generation vaccine Engerix-B™, Group II (n = 47) — the third-generation vaccine Sci-B-Vac™. Subjects received vaccines three times — on days 1, 28 and 180 of the study. HBsAb levels, rates of seroconversion (the proportion of subjects with HBsAb levels > 2.1 mIU/mL) and seroprotection (the proportion of subjects with HBsAb levels ≥ 10 mIU/mL) were assessed on days 28, 90, 180 and 210 of the study. Early seroconversion rate assessed on Day 28 was 76.60% in Group I and 93.88% in Group II (p < 0.05); seroprotection rate was 51.06 and 61.22%, respectively. These differences in the proportion of subjects who achieved seroconversion on Day 28 may indicate a faster immunological response to Sci-B-Vac™ vaccine. Statistically significant differences between the level of antibodies on days 90 and 180 (p < 0.05) were observed when analyzing the average values of HBsAb concentration in Groups I and II. The concentration of HBsAb on Day 90 was 378.68±60.95 mIU/mL in Group I, and 618.31±58.34 mIU/mL in Group II. On Day 180, the concentration of HBsAb reached 441.34±63.83 mIU/mL in Group I, and 757.72±55.14 mIU/mL in Group II. The significance of dependence of antibody level on sex, age and body weight was analyzed. It was revealed that the age of a vaccinated subject affects antibody level after administration of Engerix-B™ (p < 0.05). The results obtained suggest that there is a rapid and strong immune response to the third-generation vaccine Sci-B-Vac™. This may indicate advantage of the vaccine containing all three recombinant proteins of hepatitis B virus envelope, which, in turn, can play a key role in clinical practice for urgent prophylaxis of hepatitis B, as well as for treatment of immunocompromised conditions.

Aim: To characterize the modern trends of the hepatitis A clinic in adults with markers of the hepatitis B virus. Materials and methods: The study included 124 patients with hepatitis A, were hospitalized in Clinical Infectious Diseases Hospital named after S.P. Botkin in the period from 2012 to 2015. Diagnosis of hepatitis A and chronic hepatitis B was established on the basis of clinical and epidemiological criteria, confirmed by the results of a laboratory study. Two groups of patients were identified: 1 group – patients with hepatitis A as a monoinfection (n=85), 2 group – patients who had hepatitis A on a background of chronic hepatitis B (n=39). Results: An analysis of the age structure revealed that patients of the second group were older than the first. The analysis of gender structure established the same ratio of women and men (51,0% and 49,0%, respectively, p> 0,05) in the first group, in the second group the prevalence of women was found (64,0% and 36,0% respectively; p=0,001). General weakness, decreased appetite, and fever were more common for patients in the second group. Skin pruritus was more often in the first group. A comparative analysis of the two variants of hepatitis A showed that monoinfection of hepatitis A often occurs in mild form (47,0% and 18,0%, respectively, p=0,001). The severe form of the disease developed more often in patients of the second group (28,0% and 13,0%, respectively, p=0,02). Duration of hospitalization of patients and duration of icteric period was longer for hepatitis A on a background of chronic hepatitis B, regardless of the degree of severity. Conclusion: Modern hepatitis A in a third of cases is combined with chronic hepatitis B in people older than 40 years, and characterized by a higher frequency of severe icteric forms with severe cytolytic syndrome and requires a long hospitalization, which is accompanied by significant economic damage.

Study objective: To characterize chronic viral hepatitis C epidemic in the districts of the Northwest Federal Region and in the region as a whole. Materials and methods: Analysis of state statistics about infectious diseases in the Russian Federation as presented in Form No. 1 «Information on Infectious and Invasion Diseases» and in statistical tables developed at Methodological and Research Canter for Epidemiological Surveillance of Viral Hepatitis under Pasteur Institute of Epidemiology and Microbiology. Results: In 1996–2006, chronic hepatitis C incidence in the Northwest Federal Region was several times higher than in the Russian Federation on average. The minimum and maximum rates of newly found hepatitis C cases were 17,2о/оооо in Pskov Oblast and 93,5о/оооо in Saint Petersburg. The highest prevalence levels in all districts and in the whole region were found in the age group of 20 to 49 years. Hepatitis C prevalence in the Northwest Region is 1,7 times higher than in the Russian Federation on average (680,2о/оооо vs. 388,8о/оооо). In the year 2015 compared with 2014, the proportion of diagnoses confirmed with serological and molecular biological tests increased from 35,6 to 81,2%. However, in Leningrad Oblast, the proportion of diagnoses based solely on blood HVC antibodies increased from 57,5% to 73,1%. In Karelia, molecular biological tests were not used in 100% of cases. Conclusion: The high number of hepatitis C patients who may produce new HVC cases warrants strict registering and outpatient follow-up of infected persons and people who contacts with them at specialized clinics. The involvement of young and middle age people in HVC epidemic is prone with the formation of a population having liver cirrhosis and hepatocellular carcinoma, which makes it expedient to develop programs of antiviral therapy aimed at preventing the unfavorable outcomes of chronic viral hepatitis.

This article contains analysis of current combination treatment regimens for chronic hepatitis C after liver transplantation. Antiviral therapy with long-acting interferons and ribavirin is of low efficiency and high costs. The clinical and economic benefits of interferon-free treatment regimen for patients infected with genotype 1 HCV using dasabuvir, paritaprevir boosted with ritonavir, ombitasvir (Viekira Pak) and ribavirin have been shown. Registration and introduction into clinical practice of new direct-acting antiviral drugs will significantly expand the arsenal of tools for the treatment of recurrent HCV infections, in particular in patients infected with hepatitis C virus genotypes 2 and 3.

Aim of work: to prove necessity and safety of antiviral treatment with nucleoside analogues for severe form of acute hepatitis B.Materials and methods: The study involved 137 patients with severe form of acute hepatitis B, established by results of the identification of markers of hepatitis B virus. In 75 patients (54%) recorded the initial signs of acute hepatic encephalopathy, which were indications of hospitalization in intensive care unit. The treatment of 25 patients included nucleoside analog: telbivudine (600 mg/day) or entecavir (0,5 mg/day) – the main group. The method of «case – control» matched 25 patients in the comparison group who did not receive antiviral drugs. Monitoring of clinical and biochemical parameters were carried out once a week, the viral load – at the start of antiviral therapy and 4 weeks later.Results: In the main group noted rapid relief of major clinical symptoms of the disease (within 3–6 days). ALT levels in the main group was significantly decreased after a week of antiviral therapy, after four – reached 43,6 ± 18,7 U/L. The concentration of bilirubin in three weeks of therapy in the main group became significantly lower (p ≤ 0,05), than in the comparison group (38,0 ± 15,0 and 130,3 ± 105,1 mmol / L, respectively). After four weeks of antiviral therapy viral load decreased twice (p = 0.0001). Adverse events were not marked.Conclusion: Inclusion in the basic therapy antiviral agents allows halving the duration of stay of the patient in the intensive care unit, to prevent death, to achieve a significant improvement in laboratory parameters, in the absence of adverse events.

HBsAg earlier was always considered as the required serological marker of the current HBV-infection, and the presence of НВsAb was considered as evidence of the previous infection with the elimination of virus and the recovery. Exceptions of this rule were discovered more than two decades ago, after which it appeared the concept «occult» hepatitis В. Aim: to characterize clinical course of chronic HBV-infection HBsAg-negative (occult) depending on HBsAb levels in serum. Materials and methods : were examined 198 patients with HBsAg-negative chronic HBV-infection, with the confirmation mono-infection in the absence of factors of liver injury noninfectious etiology. Results: most of the patient was in 45–74 years old. In 53 patients (27,8%) were identified HBcAb and HBsAb titer greater than 10 IU/l: positive HBcAb and HBsAb titre from 10 to 100 IU/l in 21,2% of cases; positive HBcAb and HBsAb titer more than 100 IU/l – 5,5%. DNA HBV was determined in 7,1% of cases. Cirrhotic stage of disease diagnosed in 30,2% of patients with low levels of HBsAb and 13,2% of patients with a high level of HBsAb. Evaluation of the degree of liver cirrhosis were revealed a class C in 86,9% of cases. Patients with decompensated cirrhosis are twice as likely HBsAb in low titre than high. Conclusion : chronic HBV-infection with the serological profile of «past infection» independently of the level HBsAb can estimate as disease with the latent flow and may progression of pathologic process up to cirrhosis of the liver. These patients are subject to regular medical check once a year in a day hospital of a specialized center.

HBsAg earlier was always considered as the required serological marker of the current HBV-infection, and the presence of НВsAb was considered as evidence of the previous infection with the elimination of virus and the recovery. Exceptions of this rule were discovered more than two decades ago, after which it appeared the concept «occult» hepatitis В.Aim: to characterize clinical course of chronic HBV-infection HBsAg-negative (occult) depending on HBsAb levels in serum.Materials and methods: were examined 198 patients with HBsAg-negative chronic HBV-infection, with the confirmation mono-infection in the absence of factors of liver injury noninfectious etiology.Results: most of the patient was in 45–74 years old. In 53 patients (27,8%) were identified HBcAb and HBsAb titer greater than 10 IU/l: positive HBcAb and HBsAb titre from 10 to 100 IU/l in 21,2% of cases; positive HBcAb and HBsAb titer more than 100 IU/l – 5,5%. DNA HBV was determined in 7,1% of cases. Cirrhotic stage of disease diagnosed in 30,2% of patients with low levels of HBsAb and 13,2% of patients with a high level of HBsAb. Evaluation of the degree of liver cirrhosis were revealed a class C in 86,9% of cases. Patients with decompensated cirrhosis are twice as likely HBsAb in low titre than high.Conclusion: chronic HBV-infection with the serological profile of «past infection» independently of the level HBsAb can estimate as disease with the latent flow and may progression of pathologic process up to cirrhosis of the liver. These patients are subject to regular medical check once a year in a day hospital of a specialized center.

Comparative analysis was carried out of the effectiveness of antiviral therapy for chronic hepatitis C in patients with compensated cirrhosis and after liver transplantations. The study included 37 patients aged 49,2±8,2 years, divided into two groups: group 1 included 25 patients with liver cirrhosis (class A Child Turcotte Pugh) in the outcome of chronic hepatitis C, and group 2 12 patients after liver transplantation. Confirmation of the diagnosis of chronic hepatitis C was carried out by the detection of antibodies to hepatitis C virus at least 2 times with an interval of 6 months. Molecular biology and molecular genetic methods determined viral load and genotype. Cirrhotic stage of the disease was confirmed on the basis of the aggregate results of clinical, laboratory and instrumental examination. Antiviral therapy was performed using standard or prolonged preparations of interferon in combination with ribavirin. The main immunosuppressants were calcineurin inhibitors. The rapid and complete early virologic responses were recorded more often in group 2 (42% vs. 16 and 92% vs. 40, respectively; p0.05). Patients, who were prescribed prolonged interferon, were more likely to achieve sustained virologic response. Thus, despite the greater frequency of achieving rapid and complete early virologic response in patients with recurrent HCV infection, in the future the treatment effectiveness is comparable to the efficiency with compensated cirrhosis. In case of planning antiviral therapy, the drugs of choice may be prolonged interferon.

In the article the analysis data of observation and treatment recurrence hepatits C after liver transplantation. When performing operations on the background of the current active infection relapse is inevitable, and progression is fast. The effectiveness of antiviral therapy for immunosuppression is low. End-of-treatment response was achieved in 55,5%. Sustained virologic response was achieved in 42.9%. In one-third cases treatment was discontinuation because of adverse events.

The incidence of chronic hepatitis C in St. Petersburg is 124.4 per 100 000 population. The number of patients with liver cirrhosis is significant.Aim of this study: to examine the demographic, clinical and epidemiological characteristics of patients with cirrhosis in the results of chronic hepatitis C.Materials and methods: 100 patients with cirrhosis due to chronic hepatitis C in age 31–70 years were included. Patients with infection hepatitis viruses A and B, HIV, alcohol abuse, drug addicts, previously received antiviral therapy were excluded. Liver cirrhosis was diagnosed on the basis clinical, laboratory and instrumental investigations.Results: most patients (86,2% male and 81,7% female) are socially adapted. In 23,2% of patients antibodies to hepatitis C virus were first detected simultaneously with the diagnosis of cirrhosis. Medical procedures were the most common route of infection (25,6% male and 57,1% female). Genotype 1 was dominant (65.7%). Viral load over 800 000 IU/ml was detected in 36,7% of patients. ALT activity was normal or not more than 2 upper limit of normal in 59% of patients, AST – 47%. Normal levels of total bilirubin were recorded in 37% of cases.Conclusions: the first detection of antibodies to hepatitis C virus at the stage of cirrhosis, absence of jaundice, normal or low cytolytic activity once again confirms the need for screening for markers of hepatitis C virus. Dominance of genotype 1 is probably due on the one hand with features routes of transmission, and the other – with the speed of transformation chronic hepatitis to cirrhosis.

ЖУРНАЛ ИНФЕКТОЛОГИИ Том 5, No 3, 2013 35 Введение Проблема рецидива гепатита С после транс­ плантации печени – одна из ключевых в транс­ плантологии и инфектологии. По данным литера­ туры, в течение первого года после ортотопиче­ ской трансплантации печени (ОТП) рецидив забо­ левания в трансплантате развивается в 90–100% случаев [1]. По нашим данным, эта проблема не минует 92% реципиентов. У иммунокомпетентных лиц прогрессия хрони­ ческого гепатита С (ХГС) в цирроз печени и гепа­ тоцеллюлярную карциному занимает несколько десятков лет [2, 3]. В случае рецидива гепатита С в трансплантате течение заболевания неблагопри­ ятно и цирроз печени развивается уже через 5 лет у 30% пациентов, причем риск его декомпенсации в течение года после установления диагноза со­ ставляет более 40% [3–6]. Проведение противовирусной терапии (ПВТ) после ОТП сопровождается, кроме обычных не­ желательных явлений (гриппоподобный синд­ ром, гематологические отклонения и т.п.), рядом Эффективность противовирусной терапии рецидива хронического гепатита с у пациентов, перенесших трансплантацию печени