Viral hepatitis in children: state and prospects for solving the problem

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.

Retrospective Analysis of Experimental and Clinical Studies of Flakozid in Viral Hepatitis

Introduction. Viral hepatitis (HV) by its socio-economic significance occupies one of the leading places in human infectious pathology, therefore, the development of fundamentally new methods of prevention, diagnosis and treatment, as well as the creation of new antiviral drugs remain relevant. An antiviral herbal drug "Flakozid" has been created in VILAR, which is presented in a dosage form – 0,1 g tablets for oral administration.Аim. To analyze the experimental and clinical efficacy and safety of flakozid therapy in viral hepatitis.Materials and methods. Experimental study of the effect of flakozid on viral hepatitis A (HAV). The AGMK cell culture (BS-C-1 line) and the hepatitis A virus strain HM 175 adapted to it were used in the work. The studies were conducted in two series of experiments using different concentrations of the drug, which was introduced into cultures simultaneously with the infection of HAV. Experimental study of the effect of flakozid on viral hepatitis C (HCV). In the present experiments, a virus-containing culture fluid collected from infected cultures of chicken embryo fibroblasts containing 7,0 lg TCD50/ml of infectious HCV (genotype 1b) was used. The cytotoxic, viricidal and antiviral activity of flakozid was studied using transplanted cultures of pig embryo kidney cells (SPEV) obtained from the collection of cell lines of the D. I. Ivanovsky Research institute of virology of the Ministry of Health of the Russian Federation. In the experiments, a one-day monolayer of cells grown in 96-well plastic culture panels was used. ID50 – the concentration of the drug "Flacozid", which inhibits the development of the virus in the monolayer by 50 %, and CD50 – its minimum concentration, which causes cytotoxic destruction of 50 % of the cells of the monolayer, as well as the CTI – chemotherapeutic index, calculated as the ratio of CD50 to ID50, were determined. A well – known domestic antiviral agent, "Ribavirin", was used as a comparison drug. Clinical studies of flakozid in viral hepatitis A. The results of clinical studies of the antiviral drug "Flakozid" (0,1 g tablets) were analyzed in 258 patients with viral hepatitis A. "Flakozid" was prescribed to patients with a moderate course of the disease, 0,1 g 3 times a day for 20 days against the background of basic therapy: diet, alkaline drinking, Enterodes®. The therapeutic effect was assessed by clinical (weakness, decreased appetite, nausea, vomiting) and biochemical parameters (the level of direct bilirubin, transaminase activity), as well as by the severity of hepatolienal syndrome. Clinical studies of flakozid in viral hepatitis В. The results of clinical studies of the antiviral drug "Flakozid"(0,1 g tablets) were analyzed in 410 patients with acute viral hepatitis B, which was regarded as moderate. "Flakozid" was prescribed against the background of basic therapy: diet and detoxification therapy: 5 % glucose solution, 5 % ascorbic acid solution, "Hemodesi", at a daily dose of 0,3–0,8 g for up to 38 days. The comparison group received the same basic therapy without flakozid. The dynamics of clinical symptoms (general weakness, headache, sleep disorders, dizziness, nausea, vomiting, impaired appetite, itchy skin, pain in the right hypochondrium, jaundice, etc.), data from laboratory examination methods were evaluated, markers of hepatitis B – HBeAg and Australian antigen (HBsAg) were determined every 10 days and indicators of cellular immunity before the appointment and after 21 days of treatment; the absolute number of lymphocytes, the total number of T-lymphocytes, as well as theophylline-resistant and theophylline-sensitive cells.Results and discussion. The results of experimental studies revealed the antiviral effect of flakozid against the hepatitis A virus, confirmed during clinical studies in adult patients. Treatment with flakozid in patients with viral hepatitis A against the background of basic therapy at a daily dose of 0,3 g for 20 days led to a significant reduction in the symptoms of intoxication, a reduction in the jaundice period, normalization of the size of the liver and spleen. Treatment with flakozid as part of complex therapy of patients with acute viral hepatitis B (AHVB) of moderate severity in daily doses of 0,3–0,8 g for 38 days showed its high effectiveness, contributing to a faster disappearance of clinical symptoms of the disease (improvement of the general condition of patients, reduction of the severity and disappearance of clinical symptoms of intoxication, reducing of the jaundice period), normalization of biochemical parameters (reducing the level of bilirubin and transaminase activity), as well as elimination of HBsAg from the blood, stimulation of cellular immunity. "Flakozid" was well tolerated, did not cause allergic reactions. Based on the results of clinical studies, "Flakozid" is approved for medical use as an antiviral agent (registration number 90/248/7). The high antiviral activity of flakozid against the hepatitis C virus in cell cultures was established. In terms of the severity of the therapeutic effect, "Flakozid" was not inferior to ribavirin, and in terms of CTI it was noticeably superior.Conclusion. Treatment with flakozid in patients with viral hepatitis A and B showed its high efficiency, contributed to a faster disappearance of clinical symptoms of the disease, normalization of biochemical parameters, elimination of HCV from the blood, good tolerability. "Flakozid" is recommended in clinical practice in the complex treatment of hepatitis A and B. In vitro experiments have established a high antiviral activity of flakozid against the hepatitis C virus, which justifies the possibility of conducting clinical studies of the drug in patients with the viral hepatitis C.

Features of the Epidemic Process of Viral Hepatitis A and E in the Russian Federation

Relevance. In the Russian Federation, in recent decades, there has been a decrease in the incidence of hepatitis A (HA), at the same time, not only sporadic morbidity is registered, but also an outbreak. A decrease in the circulation of the HA virus affected the increase in the number of people without antibodies to the virus, which led to a shift in the incidence to older age groups and an increase in more severe forms of the disease. Hepatitis E (HE) is quite widespread in the world, and its specific weight in the structure of acute viral hepatitis in some countries reaches 50.0%. HE has been registered in the Russian Federation only since 2013. only in certain territories, and the incidence rates are very low. In all likelihood, this indicates a hidden circulation of the HE virus in the Russian Federation. To understand the current epidemiological situation in the incidence of HA and HE, it is necessary to understand the current trends in the epidemic process of these infections. The purpose of this work was to compile an epidemiological characteristic of the incidence of hepatitis A and E in the population of the Russian Federation at the present stage for the formation of proposals for improving the system of preventive and anti-epidemic measures.Materials and methods. To achieve this goal, a retrospective epidemiological analysis of the incidence of viral hepatitis A and E in the territory of the Russian Federation, including in federal districts, was carried out. The materials for the study were the forms of official statistical observation No. 2, 5, 6 and 23, as well as state reports «On the state of sanitary and epidemiological well-being» in the Russian Federation region for 2011–2020.Results. The conducted research allows us to compare the epidemic process of hepatitis A and E in the Russian Federation with other regions of the world. The intensity of the epidemic process of HA has significantly decreased, at the same time, there is an uneven distribution of morbidity in various federal districts. In the age structure of patients with HA, the highest incidence rates are observed among the child population and adolescents. The frequency of HA infection and a decrease in the specific weight in the structure of acute viral hepatitis were revealed. Although the territory of the Russian Federation is not endemic for hepatitis E, this disease has taken root completely. The incidence of hepatitis E in the Russian Federation is at a sporadic level. The highest incidence of HE in the Russian Federation was observed among the adult population aged 18 years and older. The issue of carrying out preventive measures, including vaccination, remains relevant.Conclusion. On the territory of the Russian Federation, there is currently a steady trend of reducing the incidence of hepatitis A. However, children under the age of 14, adolescents, as well as nonimmune adults, among whom cases of diseases are registered, are still at risk. This requires adjusting the methods of preventing this infection, which is possible not only by improving sanitary and communal improvements, but also by vaccination within the national vaccination calendar, and not only for epidemic indications. The true incidence of HE today is obviously much higher than that recorded in official statistical forms, and this requires the introduction into clinical practice (especially at the polyclinic level) of modern available tests for detecting markers of the hepatitis E virus when examining patients with symptoms of liver damage, as well as the development of effective prevention methods.

Predicting Regional Outbreaks of Hepatitis A Using 3D LSTM and Open Data in Korea

In 2020 and 2021, humanity lived in fear due to the COVID-19 pandemic. However, with the development of artificial intelligence technology, mankind is attempting to tackle many challenges from currently unpredictable epidemics. Korean society has been exposed to various infectious diseases since the Korean War in 1950, and to overcome them, the six most serious cases in National Notifiable Infectious Diseases (NNIDs) category I were defined. Although most infectious diseases have been overcome, viral hepatitis A has been on the rise in Korean society since 2010. Therefore, in this paper, the prediction of viral hepatitis A, which is rapidly spreading in Korean society, was predicted by region using the deep learning technique and a publicly available dataset. For this study, we gathered information from five organizations based on the open data policy: Korea Centers for Disease Control and Prevention (KCDC), National Institute of Environmental Research (NIER), Korea Meteorological Agency (KMA), Public Open Data Portal, and Korea Environment Corporation (KECO). Patient information, water environment information, weather information, population information, and air pollution information were acquired and correlations were identified. Next, an epidemic outbreak prediction was performed using data preprocessing and 3D LSTM. The experimental results were compared with various machine learning methods through RMSE. In this paper, we attempted to predict regional epidemic outbreaks of hepatitis A by linking the open data environment with deep learning. It is expected that the experimental process and results will be used to present the importance and usefulness of establishing an open data environment.

Possibilities of modern methods of laboratory diagnostics in the study of viral hepatitis A.

It is generally accepted that the course of viral hepatitis A is accompanied by short-term viremia, and the disease itself does not have serious consequences for the person who has recovered. The article describes a clinical case of a protracted course of viral hepatitis A with long-term persistence of the virus. Against the background of the therapy, the patient's condition improved, and by the time of discharge from the hospital on the 38th day of illness and later, with a retrospective examination on the 68th day from the onset of the disease by the method of reverse transcription PCR (RT-PCR in real time), the presence of RNA of the hepatitis A virus was confirmed in feces, which indicated a long persistence of the virus in the body. This observation indicates the need for long-term dispensary observation of patients who have undergone viral hepatitis A.

Demographics, aetiology and outcome of paediatric acute liver failure in Singapore

Introduction: The aetiology of paediatric acute liver failure (PALF) varies widely according to age, and geographic and socioeconomic factors. This study aimed to examine the epidemiology, aetiology and outcome of PALF in Singapore at a single centre. Methods: A retrospective review was performed of patients aged 0–18 years who were diagnosed with PALF from 2007 to 2019. PALF was defined by: absence of chronic liver disease; biochemical evidence of acute liver injury; and coagulopathy, non-correctible by vitamin K, defined as prothrombin time (PT) ≥ 20 seconds or international normalised ratio (INR) ≥ 2.0 regardless of hepatic encephalopathy (HE) or PT ≥ 15 seconds or INR ≥ 1.5 in the presence of HE. Results: 34 patients were included. Median age at diagnosis was 10 months (range 7 days to 156 months). The top three causes of PALF were indeterminate (41.2%), metabolic (26.5%) and infectious (26.5%) aetiologies. A metabolic disorder was the most frequent aetiology in infants < 12 months (38.9%), whereas an indeterminate cause was the most common in children > 12 months (50%). No cases of viral hepatitis A or B presenting with PALF were detected. Overall spontaneous recovery rate (survival without liver transplantation [LT]) was 38.2%, and overall mortality rate was 47.1%. Six patients underwent living-donor LT, and the post-transplant survival at one year was 83.3%. Conclusion: The aetiologic spectrum of PALF in Singapore is similar to that in developed Western countries, with indeterminate aetiology accounting for the majority. PALF is associated with poor overall survival; hence, timely LT for suitable candidates is critical to improve survival outcomes.