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Perceptions of hepatitis E have transformed over the past decade. This infection was common only in some developing countries. It is known now that hepatitis E occurs in most high - income countries and is largely a zoonotic infection. The review analyzes the relevant key publications and recommendations on the diagnosis and treatment of hepatitis E. Theproblems of diagnosis, treatment and prevention of hepatitis E caused by genotypes 3 and 4 are highlighted. It is shown that with symptoms of acute hepatitis for hepatitis E virus infection (HEV) it is advisable to test not only travelers returning from areas endemic for 1 or 2 genotypes (Asia, Africa, Mexico) and pregnant women, but also all patients, after excluding other reasons for changing liver tests. Testing for HEV is also recommended for patients with chronic liver disease with unexplained deterioration, for patients with immunosuppression and changes of liver tests, for patients with systemic manifestations of diseases of the nervous system. A combination of serological testing and nucleic acid amplification methods are recommended for the diagnosis of HEV infection. Treatment of HEV infection includes the use of antiviral therapy in severe cases; if possible, for patients who underwent transplantation of solid organs - a reduction in doses of immunosuppressive drugs for pregnant women - intensive therapy. Prevention of HEV infection is aimed at people with chronic liver diseases and receiving immunosuppressive therapy who should be excluded from the use of mollusks and poorly fried pig, boar and deer meat.

Aim of the study. To estimate efficacy and safety of 3D mode of interferon­free therapy in patients with subcompensated liver cirrhosis (LC) of HCV etiology (genotype 1b). Material and methods. Original study included the data of 66 patients (26 men and 40 women) with subcompensated LC of HCV etiology (genotype 1b) who underwent interferon­free therapy by ombitasvir/paritaprevir/ritonavir, dasabuvir and ribavirin for 12 weeks (the latter was cancelled at receiving the new data on treatment efficacy after 4 weeks of therapy) in September, 2015, before the drug instruction was updated. Mean age of patients was 56.4±10.0 years. At onset of etiological therapy 21 patients (31.8%) had Child­Pugh score of 9, eleven patients (16.7%) had Child­Pugh 8, 34 patients (51.5%) had Child­Pugh 7. The causes of inefficacy of previous modes of combined antiviral therapy (CAT) included absence of virologic response in 43.9% of the cases, recurrence of HCV replication - in 30.3%, virological breakthrough - in 16.7%, development of serious adverse effects - in 9.1%. Taking into account the change of the group quantity during the course of therapy because of treatment cancellation for safety reasons and the subsequent assessment of its efficacy in patients with early treatment cancellation, the modified «intent­to­treat» (ITT) analysis was the basic method of results evaluation. Along with that «per protocol» (PP) analysis was carried out as well. Results. During the treatment course aviremia in 14 days was achieved in 53.8% of patients (in 35 patients of 65), prompt virologic response - at 79.7% (in 51 of 64 patients). All patients underwent complete 12 week course of CAT (n=60) and those for whom treatment was canceled for safety reasons (n=3) - in terms from 14 to 30 days - sustained virologic response (SVR) in 12 weeks and SVR in 24 weeks was registered. The assessment of liver function compensation degree in 6 months after CAT termination demonstrated 3 to 4 points reduction of the Child-Pugh Score in 21 patients (33.9 %), 1 to 2 points in 35 patients (56.5 %). According to the MELD score the clinical improvement was achieved in 66.1% of patients. The early treatment termination was caused by progression of hepatic encephalopathy symptoms and/or jaundice development (4 cases). Most cases of the progression­related treatment termination due to liver failure were reversible after CAT interruption. Three lethal outcomes after the early treatment termination and 1 patients death in follow­up period were registered. Conclusion. Antiviral therapy in 3D mode for subcompensated LC is highly effective not only in those patients who received complete treatment course, but also in those with early treatment secession. Profiling of 3D therapy safety demonstrated that development of serious adverse effects during the treatment is comparable to outcomes at natural course of subcompensated LC in the absence of etiological therapy.

The majority of deaths related to complications of liver cirrhosis would have been preventable with timely diagnosis and proper treatment. However, absence of the population-based screening programs for hepatitis, an asymptomatic course of the majority of liver disorders, failures in the registration of etiologically confirmed cases of liver cirrhosis, low population awareness of its risks and of current diagnostic and management opportunities do impede the collection of reliable epidemiological data on the incidence and prevalence of liver disorders including their end-stages, and on the related mortality of the population; as a consequence, all these factors hinder a comprehensive assessment of the medical and social burden of hepatic disorders. Medical registries are the single system for their registration and follow-up. Analysis of data from the Moscow Regional Registry of patients with liver disease has shown that the leading cause of liver cirrhosis is HCV infection (66%), with alcoholic liver cirrhosis ranking second (16.1%). There is a trend towards higher proportions of liver cirrhosis as an outcome of HCV hepatitis among newly referred patients (7.2% in 2012 and 10.6% in 2016). HCV genotype characteristics determine the rates of the disease progression: in those with genotype 3, liver cirrhosis would occur at an earlier age (51.8% of patients aged from 26 to 45) than with genotype 1 (58.7% of patients aged from 46 to 65). In older patients, various comorbidities can contribute to the development of liver cirrhosis. Among patients with HBV infection, 4.9% have liver cirrhosis, and most of patients receive antiviral treatment with nucleoside/nucleotide analogues. The highest percentage of liver cirrhosis has been found in the patients with chronic D hepatitis (46/116, 39.7%). In 10.3% of the patients with chronic D hepatitis, the aggressive course of the disease leads to primary liver cancer. Thus, the necessity of the development of prevention measures and early detection of liver disorders, as well as modernization of the public healthcare system at all stages of medical care should be recognized as the short-term goals, in addition to the search for highly effective etiologic treatment and making it available within the state-financed programs.

Background: Epidemiological characteristics of chronic hepatitis C virus (HCV) infection presented in the literature are not representative for the real situation with its incidence and prevalence in the Russian Federation. In the Moscow Region, which is the second largest population in the Russian Federation (7.2 million people), the Moscow Regional Registry of patients with hepatic disorders has been continuously maintained since 2010, as well as screening programs for anti-HCV positive individuals. Analysis of this data allows for generalization of the results obtain to the general population and for description of the prevalence of the infection among adult population of the Russian Federation. Aim: To analyze the epidemiological situation with chronic hepatitis C in the Moscow Region. Materials and methods: We analyzed data from the Moscow Regional Registry of patients with hepatic disorders as per April 2016, as well as the results of large scale screening of the population of the Moscow Region with oral express test for anti-HCV antibodies (OraQuick HСV Rapid Antibody Test). Based on the registry, we assessed the following parameters of the patient cohort with chronic HCV infection (n = 17 182): age, gender, HCV genotype, grade of liver fibrosis, allele variants of interleukin 28В. Within the large scale screening program among the population of the Moscow Region, 1447 individuals from 6 districts of the region were screened for anti-HCV antibodies. Results: As per April 2016, the proportion of patients with chronic viral hepatitis in the Registry was 75.3% (n = 12 938 of 17 182). The vast majority of them (80.3%, or n = 10 393) had chronic hepatitis C, with 84% (n = 8726) of referrals were patients of productive age (from 20 to 50 years). 8.4% (n = 873) of all HCV infected patients had liver cirrhosis. Although the proportion of patients with cirrhosis was negligibly low (< 1.5%) in patients below 30 years of age, it was progressively increasing with age, with a maximum of 23.8% in those above their 50-es. As far as the HCV genotype distribution is concerned, it was as follows: genotype 1, 54.1% (n = 5622) of patients, genotype 2, 7.2% (n = 747), genotype 3, 38.4% (n = 3990). According to the results of assessment of IL28B genetic polymorphisms (n = 3212), СС rs12979860, which is associated with the most favorable sensitivity to interferon α, was found in 27.5% (n = 883), СТ allele, in 58.4% (n = 1876), and ТТ in 14,1% (n = 453). Prevalence of HCV infection in the Moscow Region, assessed by the screening program, is 1.38% of adults, or 77 200 anti-HCV positive persons, whereas estimated number of patients with chronic hepatitis C may amount to 54 000 to 61 700. Conclusion: HCV infection is the most prevalent among other viral hepatites in the Moscow Region (80.3%), and the largest numbers of infected individuals are of productive age. Almost three quarters of these patients are referred for medical care at the stage of minimal liver injury, and antiviral therapy can be used on an elective basis. Knowing the proportion of patients with liver cirrhosis (8.4%) allows for planning of the need in emergency treatments. The true prevalence of HCV infection estimated from the results of the screening program is at least 5-fold higher than that in the Registry. This indicates the necessity to upgrade the system of primary assessments. In particular, it seems reasonable to include detection of anti-HCV antibodies into the list of obligatory screening laboratory tests.

The structure of HCV genotypes/subtypes and dynamics of its changes in a cohort of adult patients with chronic hepatitis C (n = 17229) was studied during 2008-2015 in the Moscow region. The prevalence of subtypes 1b and 3A HCV, whose relative density have made 47.5% (95%CI 46.8 - 48.3%) and 39.4% (95% CI 38.7 - 40.2 per cent) respectively was revealed. The average proportion of subtype 1A HCV was 5.4% (95%CI of 5.1 - 5.8%) and genotype 2 - 7.2% (95% CI 6,8 - 7,6%). It was established that the dynamics of 1b subtype HCV relative density was characterized by a moderate decline rate of 1.3% per year, while the proportion of subtype 3A HCV increased (+2.9% per year). The differences in the ratio of subtypes 1b and 3A HCV were revealed when dividing the patients by gender. The subtype 1b HCV was more frequently identified in women during the observation period. In the cohort of male patients a shift of the leading HCV subtype was detected - since 2010, the 3A subtype HCV was identified with a higher frequency than subtype 1b HCV. It was shown that in patients under 30 years the proportion of subtype 3A HCV was higher than in the age group older than 30 years, regardless of gender.

Background: The beginning of a new era of direct acting antivirals sets up its own rules, that is, to achieve the highest efficacy with the shortest duration of treatment. It is assumed that the use of the first generation of direct acting antivirals, similarly to interferon-free regimens, would allow for personalization of approaches to their prescriptions.Aim: To identify the most important parameters that can predict the greatest efficacy of triple antiviral therapy of 12 week duration in patients with chronic hepatitis C genotype 1.Materials and methods: The study included 204 patients with chronic hepatitis C virus (HCV) genotype 1 at an early stage of liver disease (METAVIR score F0-F2), who were either treatment-naive or had a history of relapse after standard of care antiviral therapy. In addition to routine work-up, all patients were screened for IL28B polymorphism; in the course of the treatment viral kinetics was assessed by an ultrasensitive polymerase chain reaction (PCR) (with lower limit of quantification of 12 IU/ml). Duration of the triple therapy (pegylated interferon-α2a, ribavirin and telaprevir) was reduced to 12 weeks if a rapid virological response was achieved; otherwise the patients continued their treatment in according with guidelines. Results: A complete rapid virological response was achieved in 174 patients (81.6%), in whom the duration of triple therapy was 12 weeks. According to the protocol, 25 patients with a partial rapid virological response continued their standard antiviral therapy for 12 weeks more. In those who achieved a rapid virological response, there was an association between IL28B-CC genotype at rs12979860 and maintenance of zero viremia at 12 weeks after termination of antiviral therapy (r = 0.38, p < 0.001). In all such patients there was a stable virological response at 12 weeks of the follow-up. Monitoring of viral load after 14 days of antiviral treatment was not predictive of its success. The preliminary results of a shortened (12 week) course of triple telaprevir-based viral therapy allowed to identify the most significant parameters of 100% efficacy, i.e., absence of the virus in blood at 12 weeks after termination of antiviral therapy. Conclusion: A 12 week course of triple telaprevir-based combination therapy is an optimal regimen for achievement of a stable virological response after 12 weeks of the follow-up in treatment-naïve patients with HCV genotype 1 or with a relapse after previous conventional antiviral treatment, who have IL28B – CC polymorphism, are at an early stage of liver disease and who achieve a rapid complete virological response confirmed by a highly sensitive PCR.

Treatment of chronic hepatitis B during pregnancy is an extremely complicated issue. Despite implementation of immune prophylaxis, a significant proportion of babies born by mothers with high viral load are infected by hepatitis B virus. Cumulative data suggest that antiviral therapy in the 3 trimester of pregnancy is an effective intervention in the event of unsuccessful immune prord phylaxis. To minimize fetal effects of nucleoside and nucleotide analogues, antiviral therapy during pregnancy should be administered to mothers with high risk of disease progression and/or uncontrolled hepatitis B virus infection. The safety data obtained indicate that telbivudine and tenofovir can be used during pregnancy. Nevertheless, antiviral therapy requires a thorough assessment of the risk to benefit ratio.