In most cases, EBV mononucleosis in hospitalized children occurs in a typical form, with a classical clinical picture. Cases of hepatitis, as the leading syndrome in EBV infection, are extremely rare. The article presents a clinical case of atypical onset of infectious mononucleosis of EBV etiology, which started with liver damage syndrome. This clinical experience gives an opportunity to run diagnostics of herpesvirus infections in cases of nonspecific liver damage.

Патогенетическая связь между состоянием микробиоты кишечника и заболева ниями печениАНАЛИТИЧЕСКИЕ ОБЗОРЫ 1 Федеральное государственное бюджетное учреждение «Детский научноклинический центр инфекционных болезней Федерального медико-биологического агентства», 197022, г.Санкт-Петербург, Российская Федерация 2 Федеральное государственное бюджетное образовательное учреждение высшего образования «Санкт-Петербургский государственный педиатрический медицинский университет

На фоне успехов здравоохранения, в том числе вакцинопрофилактики, и повышения уровня санитарного контроля проблема острых гепатитов с тяжелым течением несколько потеряла свою актуальность. Основной проблемой инфектологии в последние годы стал SARS-CoV-2. Однако мир столкнулся с новой вспышкой заболевания, этиология которого до настоящего времени достоверно не установлена. Мишенью в этом случае стала печень, а восприимчивой группой населения – дети. В апреле 2022 г. ВОЗ сообщила о выявлении случаев тяжелого острого гепатита неясной этиологии у детей. На конец мая 2022 г. известно о 650 случаях заболевания у детей в возрасте от 1 месяца до 16 лет в 35 странах мира. В ≈10% случаев гепатит осложнился формированием печеночной недостаточности, что потребовало трансплантации печени. Зарегистрировано как минимум 11 летальных исходов. По первым данным, заболевание не имеет связи с новой коронавирусной инфекцией и вакцинацией от нее. Основной рабочей гипотезой является аденовирусная этиология гепатита. Поиски возбудителя продолжаются. В соответствии с определением рабочего случая ВОЗ в качестве вероятного случая заболевания рассматривается «острый гепатит (не А – не Е) с уровнем печеночных трансаминаз (АЛТ и/или АСТ) в сыворотке >500 Ед/л в возрасте 16 лет и младше с 1 октября 2021 г.». В статье собраны сведения, касающиеся этой патологии, опубликованные на данный момент, и рассмотрены основные версии относительно ее этиологии. Against the backdrop of advances in health care, including vaccination, and an increase in the level of sanitary control, the problem of acute hepatitis with a severe course has somewhat lost its relevance. SARS-CoV-2 has become the main problem of infectology in recent years. However, the world is faced with a new outbreak of the disease, the aetiology of which has not yet been reliably established. The target in this case was the liver, and the susceptible population was children. In April 2022, WHO reported the detection of cases of severe acute hepatitis of unknown aetiology in children. To date, 169 cases of the disease have been reported in children aged 1 month to 16 years in 12 countries. In 10% of cases (17 children), hepatitis was complicated by the formation of liver failure, which required liver transplantation. According to the first data, this disease has no connection with a new coronavirus infection and vaccination against it. The main working hypothesis is adenoviruses, because they were found in at least 74 patients. The search for the pathogen continues. According to the WHO working case definition, a probable case is considered to be "acute hepatitis (non-A-non-E) with serum transaminase levels >500 U/L at age 16 years and younger from 1 October 2021". The article contains information related to this pathology, published at the moment and considers the main versions regarding its aetiology.

The problem of viral hepatitis (VH) today is an acute problem for the world healthcare system. Along with the COVID-19 pandemic, the VH pandemic claims up to 1.5 million lives annually. Since 2016, the Russian Federation has launched a WHO program aimed at combating VH. One of the first steps on the path of global elimination is getting rid of the virus in the small groups, among which micro-elimination in the child population is one of the promising areas. This review is devoted to the current state of the problem of VH in children in the Russian Federation today. The success of vaccine prevention (against viral hepatitis A and B) made it possible to achieve results in the form of a significant decrease in the incidence of children, minimizing the risk of perinatal infection. However, in recent years, there has been a progressive decline in vaccination coverage. This is mainly due to the growing popularity of anti-vaccination lobbies, a decrease in the awareness of patients and health workers about the need for timely vaccination, as well as the introduction of restrictive measures to prevent a new coronavirus infection. The emergence of mutant, "vaccine-eluting" strains, which are also resistant to available antiviral drugs, is another serious problem on the way to eliminating viral HBV. In the field of treating children with HBV, the possibilities are extremely limited, only 2 drugs are available, one of which (tenofovir alafenamide) is available only from the age of 12. Registration of direct antiviral drugs for the treatment of adolescents with chronic hepatitis C has made it possible to bring closer the goal of microelimination of the virus in children. However, the high cost of drugs poses a challenge for the state to introduce long-term benefit programs to ensure the availability of treatment. In addition, at the moment, the treatment of young children in our country remains a prospect for the future. Thus, despite significant advances in the strategy for the elimination of viral hepatitis, a number of problems remain relevant and present significant difficulties in achieving the global goal.

Токсоплазмоз является широко распространенной паразитарной инфекцией. В большинстве случаев заболевание протекает бессимптомно. Тяжелые случаи токсоплазмоза обычно ассоциированы с иммунодефицитами (в том числе ВИЧ-инфекцией). Эта тема хорошо освещена в литературе. Внимание уделяется также врожденному токсоплазмозу. Существенное значение отводится токсоплазменной инфекции в среде офтальмологов (хориоретиниты). В то же время ввиду легкого течения без специфических признаков висцеральный токсоплазмоз у иммунокомпетентных лиц оказывается недооцененным и зачастую воспринимается практикующими врачами как казуистичный. В статье приведены данные, подчеркивающие значимость токсоплазменной инвазии у иммунокомпетентных пациентов. Приведены клинические примеры висцерального токсоплазмоза c поражениями печени из журнальных публикаций. Проанализирована распространенность токсоплазмоза у пациентов с фоновой патологией печени. Приведенные данные подчеркивают значимость данного паразитоза и необходимость исключения его в клинически неясных случаях висцеральной патологии у иммунокомпетентных пациентов. Toxoplasmosis is a widespread parasitic infection. In most cases, the disease is asymptomatic. Severe cases of toxoplasmosis are usually associated with immunodeficiencies (including HIV infection). This topic is well covered in the literature. Attention is also paid to congenital toxoplasmosis. Toxoplasma infection is given significant importance among ophthalmologists (chorioretinitis). At the same time, due to the mild course without specific signs, visceral toxoplasmosis in immunocompetent individuals is underestimated and is often perceived by practitioners as casuistic. The article presents data emphasizing the importance of toxoplasma invasion in immunocompetent patients. Clinical examples of visceral toxoplasmosis with liver lesions from journal publications are presented. The prevalence of toxoplasmosis in patients with underlying liver pathology was analyzed. The data presented emphasize the importance of this parasitosis and the need to exclude it in clinically unclear cases of visceral pathology in immunocompetent patients.

Aim. To determine the number of children with chronic hepatitis C in the Russian Federation, including, who have received antiviral treatment, taking into account their age, the genotype of the virus, as well as the therapy regimens used.Materials and methods. The analysis of specially developed statistical reporting forms was carried out, the filling of which was carried out in September 2020 by specialists from 268 medical organizations from 37 constituent entities of the Russian Federation, which are part of 8 federal districts.Results. In September 2020, 2,160 children with chronic hepatitis C virus infection aged 0 to 17 years were under observation in 268 medical organizations, including 50.7% females and 49.3% of males. The number of children in the age group from 12 to 17 years was 42.9%, from 6 to 11 years – 34.5%, from 3 to 5 years – 16.2% and from 0 to 2 years – 6.4%. The genotype of the virus was determined in 1388 (64.3%) children. The proportion of children with genotype 1 was 58.6%, with genotype 3 – 37.2%, with genotype 2 – 4%. Only 141 (8.8%) children with chronic hepatitis C virus infection have been received antiviral therapy. 1465 (91.2%) children were not treated, but 153 (9.5%) of them received therapy earlier, without achieving a sustained virological response. Direct-acting antiviral agents treatment was carried out to 120 children (85.1%), of whom glecaprevir + pibrentasvir was received by 85 children (70.8%) in 20 regions, sofosbuvir + ledipasvir – 14 children (11.7%) in 6 regions, sofosbuvir – 14 children (11.7%) in 6 regions, daklatasvir – 7 children (5.8%) in 4 regions. Children are removed from dispensary observation after achieving a stable virological response in accordance with the current regulatory documents in 26 regions of the Russian Federation (70.3%).Conclusion. In 2020, less than 10% of children under management received antiviral therapy for chronic hepatitis C virus infection in the Russian Federation. It is necessary to approve the state program for the treatment of viral hepatitis, one of the directions of which should be the provision of all children with chronic hepatitis C virus infection with modern highly effective antiviral drugs. It is also necessary to conduct clinical trials to assess the safety and efficacy of direct-acting antiviral agents for children with chronic hepatitis C virus infection in order to ensure the possibility of their earlier prescription.

The article presents a case of an unusual course of chickenpox in a young child (1.5 months). The development of acute hepatitis against the background of the course of the disease is described.This clinical observation clearly demonstrates that the varicella zoster virus, like other viruses from the herpes family, is secondary hepatotropic and is capable of causing acute hepatitis. This experience allows us to recommend assessing liver function in patients with chickenpox, and, if abnormalities are found, supplement the standard therapy with the appointment of hepatoprotectors.

Введение. Хронический гепатит С (ХГС) занимает лидирующую позицию среди всех хронических гепатитов. Около 71 миллиона человек в мире инфицированы вирусом гепатита С (ВГС), среди них, по разным оценкам, от 2,1 до 5 млн составляют дети до 15 лет. В большинстве случаев заболевание в детском возрасте протекает бессимптомно, однако с возрастом повышается риск развития фиброза и связанных с ним осложнений, что требует динамического контроля и своевременного назначения противовирусной терапии. Цель исследования. Определить эпидемиологические особенности и характер течения вирусного гепатита С у детей, инфицированных в раннем возрасте; проанализировать эффективность новых схем терапии препаратами прямого противовирусного действия в сравнении с терапией препаратами интерферона. Материалы и методы. В группу наблюдательного исследования вошли 559 детей с установленным диагнозом ХГС. Диагноз был подтвержден серологически (методом ИФА) и молекулярно-генетически (методом полимеразной цепной реакции - ПЦР). Степень фиброза оценивалась по результатам эластографии печени (Fibroscan). Результаты. Преобладающее большинство детей были инфицированы ВГС в результате перинатального контакта. Спонтанный клиренс отмечался не более чем в 20% случаев. По полученным данным, девочки заражались чаще мальчиков, однако с большей частотой элиминировали вирус. ХГС в детском возрасте характеризовался гладким, малосимптомным течением, однако 12% пациентов имели начальную стадию фиброза. УВО при использовании интерфероновых (ИФН) схем был достигнут у 40-53% пациентов с 1-м генотипом, у 92-100% пациентов со 2-м и 3-м генотипами. Эффективность терапии α-ИФН с рибавирином (РВ) составила 72%, пег-ИФН с РВ - 81,8%, комбинацией пег-ИФН + РВ в сочетании с каскадной плазмофильтрацией - 89,2%. Применение препаратов интерферона сопровождалось развитием нежелательных явлений, наиболее тяжело переносили введение препарата подростки старше 12 лет. Среди побочных реакций чаще всего наблюдался гриппоподобный, астеновегетативный синдромы (до 97%), несколько реже отмечались диспептические расстройства, снижение массы тела, алопеция, нервно-психические расстройства. В единичных случаях был спровоцирован дебют аутоиммунных заболеваний. На базе нашего центра подтверждено влияние полиморфизма генов rs8099917 и rs12979860 IL28B на вероятность спонтанной элиминации вируса гепатита С, а также на эффективность ПВТ. С 2019 г. начата терапия препаратами прямого противовирусного действия (ПППД), которая показала 100% эффективность при развитии минимальных нежелательных явлений. Выводы. Заболеваемость ХГС в настоящее время остается на высоком уровне. Несмотря на малосимптомное течение заболевания у детей, с возрастом значительно повышается риск развития прогрессирующего фиброза печени, жизнеугрожающих осложнений. Применение препаратов прямого противовирусного действия у детей позволяет не только своевременно начать терапию ХГС, но также избежать серьезных нежелательных явлений, связанных с лечением препаратами интерферона. Introduction. Chronic hepatitis C (CHC) occupies a leading position among all chronic hepatitis. There are about 71 million people in the world infected with the hepatitis C virus (HCV). Among them there are 2.1-5 million children under 15 years of age according to various estimates. In most cases, the disease in childhood is asymptomatic, however, with age, the risk of fibrosis and associated complications increases, that`s why requires dynamic control and timely administration of antiviral therapy. Purpose of the study. To determine the epidemiological features and nature of the course of viral hepatitis C in children infected at an early age; to analyze the effectiveness of new regimens of therapy with direct antiviral drugs in comparison with interferon therapy. Materials and methods. There are 559 children with an established diagnosis of CHC included in the observational study group. The diagnosis was confirmed serologically (by ELISA) and molecular- genetically (by polymerase chain reaction - PCR). The degree of fibrosis was assessed by the results of liver elastography (Fibroscan). Results. The vast majority of children were infected with HCV as a result of perinatal contact. Spontaneous clearance was noted in no more than 20% of cases. According to the data obtained, girls became infected more often than boys, but eliminated the virus with a greater frequency. CHC in childhood was characterized by a smooth, low-symptom course, but 12% of patients had an initial stage of fibrosis. SVR after using interferon (IFN) regimens was achieved in 40-53% of patients with genotype 1, 92-100% in patients with genotypes 2 and 3. The effectiveness of therapy for a-IFN with ribavirin (RV) was 72%, peg-IFN with RV - 81.8%, the combination of peg-IFN + RV in combination with cascade plasma filtration - 89.2%. The use of interferon preparations was accompanied by the development of undesirable phenomena; adolescents over 12 years of age hardly tolerated the administration of the drug. More often observed adverse events were flu-like, asthenovegetative syndromes (up to 97%), dyspeptic disorders, weight loss, alopecia, and neuropsychiatric disorders were noted somewhat less frequently. In isolated cases, the debut of autoimmune diseases was provoked. On the basis of our center, the influence of the polymorphism of the rs8099917 and rs12979860 IL28B genes on the probability of spontaneous elimination of the hepatitis C virus, as well as on the effectiveness of the AVT, has been confirmed. Since 2019 therapy when direct antiviral therapy (DAA) was started, it showed 100% efficiency with minimal adverse events. Conclusions. The incidence of CHC currently remains at a high level. Despite the low-symptomatic course of the disease in children, the risk of developing progressive liver fibrosis and life-threatening complications increases significantly with age. The use of drugs with direct antiviral action in children allows not only to start therapy for CHC in a timely manner, but also to avoid serious adverse events associated with treatment with interferon drugs.

The results of clinical and laboratory examination of 107 children suffering from chronic hepatitis B or C were analysed. The biochemical criteria of the endogenous intoxication were investigated. Specific blood tests with antiviral drugs were conducted before the treatment and individual therapy schemes were assigned according to the tests' results. The early and sustained virological response rates during the individual antiviral treatment of the children with chronic hepatitis C proved to be 70.83 and 62.5% respectively.

Liver transplantation today is the only radical method of treatment decompensating fulminant and chronic liver failure. The operation technic and patient care improvement made it possible to achieve a high survival rate. Transplantation has become an available and safe method for children, including patients weighing less than 10 kg. However, at the moment there are a number of unsolved problems. Postoperative complications can significantly affect the results of transplantation. This article provides a Russian and foreign literature overview, reflecting the achievements in the field of liver, identifying current problems and solutions.

Протокол № 2, Приложение 1 УТВЕРЖДЕНЫ XVI Съездом НОГР Москва, 24-25 ноября 2016 г. Президент НОГР д.м.н., проф. Л. Б. Лазебник

The analysis of serological efficiency and duration of maintaining specific immunity at the children imparted by various vaccines against hepatitis B within the national calendar of inoculations in the territory of St. Petersburg is submitted. It is revealed that high credits of antibodies (more 100 mME/ml) were more often observed at children in the first 3 years after vaccination (68.2%). Eventually levels of antibodies decreased, and in 5 years protective credits have remained at 84.5% examined, the number of patients with a caption of antibodies less than 10 Mmeml has grown from 8.5 to 15.5%.

Recently the actual direction is development of programs of rehabilitation of the second stage of recovering of infectious diseases children. The purpose of this work is justification of need of the organization of offices of rehabilitation in a children's infectious hospital according to Order of the organization of medical rehabilitation. The retrospective analysis of clinical records of the patients who have arrived on treatment in clinical divisions of Federal State Budgetary Institution of Research of Children's Infections of Russia in 2011—2012 is carried out. It is established, that among surveyed 14 363 for 2 years of patients (in a year on the average more than 7000 children) — about 40% (2800 patients a year) children for whom rehabilitation actions of the second stage in the conditions of a hospital, including carrying out a diet therapy, physiotherapy exercises, physical therapy and pharmacotherapy are necessary. On a profile of infectious patients for rendering the rehabilitation help it is expedient to organize 2 offices on 30 beds: for treatment of children with consequences of neuroinfections and children with somatic pathology. The organization of two offices for carrying out medical rehabilitation of the second stage to recovering infectious diseases children taking into account recommended standards on equipment, according to the Order of the organization of medical rehabilitation, will allow to give high-tech help to patients and to prevent development of complications.

The article presents the result of observation of children born to mothers with HBV infection and peculiarities of primary chronic hepatitis B in the dynamics.

The aim of the study: to establish the rate of the vertical transmission of HCV infection and justify the usefulness of the drug a-IFN2b (Viferon®) in children with perinatal infection with hepatitis C virus (HCV) at the early stages of the disease. There were examined 465 children aged 2.5 months to 3 years old (at the time of the enrollment in the study), born to mothers with HCV infection and the frequency of transmission from mother to child was established to be is 7.1% (33 cases). In 54.5% the genotype 1b was recorded, in 3% 1a, and in 6.0 % 2 genotype. Viferon® drug in doses of 3х10 6IU/m 2 was introduced to 17 infants aged from 3 to 12 months (duration of the course: 6 months in cases with 3, 2 genotype and 12 months in patients with genotype 1). The efficacy of therapy was 58.8 % (RNA HCV (-) 10 cases. In prescription the drug to children under 6 months the efficacy was 62.5%, under 6-12 months 44.4%. In the control group (16patients) spontaneous viral clearance was established to be in 18.7% of cases. The medication did not cause adverse effects and was well tolerated by children. In none out of the 17 children treated with the drug Viferon®, we have not reported adverse events (clinical symptoms, abnormalities in the hemogram and biochemical indices). The obtained data confirm the expediency of the early use of antiviral drug Viferon® in the treatment of children with perinatal HCV. Nо significant difference in the efficacy of therapy in different genotypes of the virus was identified. Virtually in all children (9 out of 10 children) responded to Viferon® therapy, there was noted Sustained Viral Response

Recently, the share of children with verified neonatal hepatitis induced by genetic predisposition, malformations of biliary tracts, inborn infections with affection of hepatobiliary system increased. The comprehensive biochemical examination of 62 children aged from 1.5 months to 2 years old with diagnosis of neonatal hepatitis. The changes of standard indicators of cytolysis, cholestasis and protein metabolism were on average moderate in group with reliable increase of protein concentration of acute phase of inflammation. The peak changes of biochemical indicators during primary examination are revealed in group of children with malformations of hepatobiliary system conditioned by viruses of herpetic group and in the process of development of expressed fibrosis of liver up to first year of life. The detection of proteins of acute phase makes it possible to objectively evaluate the presence of prolonged inflammatory process in liver and to promote prognosis of course of neonatal hepatitis in children of early age and timely correction of therapy and improvement of outcomes of disease. The detection of C-reactive protein, alpha2-macroglobulin and alpha1-antitripsin is recommended to be included into algorithm of examination of children with neonatal hepatitis.