В конце декабря 2019 г. в Китайской народной Республике началась вспышка неизвестной пневмонии, вызванная новым коронавиру-сом SARS-CoV-2 (severeacuterespiratorysyndromecoronavirus — коронавирус тяжелого острого респираторного синдрома). Всемирная организация здравоохранения 11 февраля 2020 г. присвоила официальное название SARS-CoV-2-инфекции, — COVID-19 («CoronaVirus Disease 2019» — заболевание, вызванное новым коронавирусом 2019). Пневмония является ведущей клинической формой COVID-19. Однако по мере распространения пандемии COVID-19 и анализа клинических данных у заболевших стали выделять симптомы, не характерные для «аномальной» пневмонии. Описаны неврологические проявления, изменения кожи, поражения глаз и др. Внелегочное присутствие SARS-CoV-2 обнаружено также в холангиоцитах. Среди возможных факторов повреждения печени рассматривается вирус-индуцированное влияние, системное воспаление («цитокиновый шторм»), гипоксия, гиповолемия, гипотония при шоке, лекарственная гепатотоксичность и др. У 14-53% пациентов с COVID-19 могут регистрироваться изменения биохимических показателей, которые, как правило, не требуют медикаментозной коррекции. Весьма редко развивается острый гепатит. Однако особое внимание следует уделять пациентам с COVID-19, относящимся к группе риска — перенесшим трансплантацию печени, получающим иммуносупрессанты, а также в случаях декомпенсации цирроза, развитии острой печеночной недостаточности на фоне хронической, гепатоцеллюлярной карциномы, при проведении противовирусной терапии. Необходим постоянный обмен и открытый доступ к научным данным, новым технологиям, обновляющимся руководствам.

Since August 2012, universal single-dose vaccination in children aged at least three years has been implemented in the Republic of Tuva, which was previously the region most affected by hepatitis A in Russia. The objective of this cross-sectional study was the assessment of the immunological and epidemiological effectiveness of vaccination program five years following its implementation. In the pre-vaccination period, anti-HAV antibody detection rates in Tuva was 66.0% [95% CI: 56.3–74.6%] in children aged 10–14 years and reached a plateau (>95%) by age 20–29 years. Annual incidence rates in children under 18 years of age peaked at 450–860 per 100,000 in pre-vaccination years but dropped to 7.5 per 100,000 in this age group and to 3.2 per 100,000 in the total population one year after the start of vaccination. Since 2016, no cases of hepatitis A has been reported in Tuva. Serum anti-HAV antibodies were quantified in samples from healthy children following single-dose vaccination. Protective anti-HAV antibody concentrations (≥10 mIU/mL) were detected in 98.0% (95% CI: 96.2–99.0% (442/451)) of children tested one month after single-dose immunization, in 93.5% (95% CI: 91.0–95.4% (477/510)) and in 91.1% (95% CI: 88.2–93.4% (422/463)) of children one year and five years after single-dose immunization, respectively. Anti-HAV antibody geometric mean concentrations were similar in sera collected one month, one year, and five years following single-dose vaccination: 40.24 mIU/mL, 44.96 mIU/mL, and 57.73 mIU/mL, respectively (p > 0.05). These data confirm that single-dose vaccination is an effective method of bringing hepatitis A under control in a short period of time in a highly endemic region.

Выявление синдрома Жильбера методом пиросеквенирования у пациентов в реальной клинической практике

Background. Enzymopathic jaundices are manifested by intermittent hyperbilirubinemia, no changes in the structure of the liver, no hemolysis, Rh-conflict as well as cholestasis being noted. These jaundices include Crigler-Najjar syndrome type I, Crigler-Najjar syndrome type II and Gilbert's syndrome. They are characterized by an autosomal recessive inheritance due to the presence of mutations and polymorphisms in uridine 5'-diphosphate-glucuronosyltransferase gene (UGT1A1) leading to a decrease of the enzyme activity or to its complete loss. Objective. To demonstrate the peculiarities of diagnosis and treatment of a rare case of hereditary unconjugated hyperbilirubinemia - a combination of Crigler-Najjar syndrome type II and Gilbert's syndrome. Material and methods. Clinical observation of a patient G. aged 19, who was examined and treated at the Department of gastroenterology of a multidisciplinary hospital in Moscow in January 2021. Results. The patient G. has had icteric sclerae and skin since birth; he occasionally suffers from easy fatigability and general malaise. Physical examination revealed no changes (except for icteric discoloration). An increase in unconjugated bilirubin up to 270 μmol/L (median - 170 μmol/L) was detected. The molecular genetic study of UGT1A1 gene identified mutations in exon 4 Val378Asp (2002) and Arg108Cys as well as polymorphism 6/7TA in the promoter region, confirming the diagnosis of autosomal recessive inherited disease – a combination of Crigler Najjar syndrome type II and Gilbert's syndrome (heterozygous state), complicated by the development of hepatic encephalopathy stage 2. There was noted a significant decrease in unconjugated bilirubin up to 170.5 μmol/L, as well as improvement in general condition – reduced fatigue and weakness during the treatment with microsomal enzyme inducer (phenobarbital) and hyperammonemia corrector (ornithine aspartate). Conclusions. The use of molecular genetic analysis allows tailoring strategies for patient-specific disease diagnostics, treatment and prevention. The preservation of quality of life within satisfactory level is achieved through elimination of adverse effects provoking the development of this syndrome and through control of risk factors.

COVID-19 (coronavirus disease 2019, a disease caused by a new coronavirus 2019) continues to threaten world public healthcare. Epidemiological data indicate that patients with metabolic disorders and chronic illnesses are most susceptible to SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). Potential factors for organ involvement include systemic hyperimmune-mediated inflammation due to the “cytokine storm”, cytopathic effects, hypoxia, drug toxicities, etc. In addition, SARS-CoV-2, by interaction with ACE2 (angiotensin-converting enzyme 2) receptors in the vasculature endothelium results in endothelial dysfunction, increased permeability, microcirculatory abnormalities, vascular thrombophilia and thrombus formation. The diagnosis of COVID-19 is confirmed by detection of SARS-CoV-2 RNA in biological samples and serum antibodies. The infection is associated with leukopenia and thrombocytopenia, increased С-reactive protein, ferritin, lactate dehydrogenase, and D-dimer. Abnormalities in functional liver tests seen in COVID-19 are associated with progression and severity of the infection. The mechanism of direct cytotoxicity due to active SARS-CoV-2 replication in hepatocytes are not fully understood and is likely to be related to potential proliferation of hepatocytes, liver injury in response to systemic inflammation, and development of drug hepatic toxicity. We present a clinical case of drug-induced hepatitis in a patient with COVID-19 treated with tocilizumab, an inhibitor of interleukin 6 receptors. Prolonged increase in blood enzymes after treatment cessation is likely related to a longer half-elimination time of tocilizumab, which affects the oxidation-reduction system of liver cytochromes. Patients with chronic liver disorders are more vulnerable to clinical sequelae of СOVID-19, while the infection is frequently associated with hypoxia and hypoxemia due to severe pneumonia or the “cytokine storm”. In addition, patients who have been diagnosed with liver cirrhosis are at high risk of morbidity and mortality due to their higher proneness to infections, first of all, due to systemic immune deficiency that was demonstrated in the second clinical case. Decompensated liver cirrhosis is related not only to a higher risk of more severe COVID-19, but also to progression of chronic liver disease as such. To achieve effective results of causal and nosotropic therapy for COVID-19, it is highly significant to provide thorough clinical monitoring, tailored approach to the treatment of each patient with consideration of their comorbidities, immune status, and drug interactions.

An increase in the amount of ammonia-ammonium in tissues plays a significant role in the development of human pathology. The appearance of an increasing number of publications emphasizes the urgency of the problem. A team of experts who took part in the XXVII Congress of the Scientific Society of Gastroenterologists of Russia (NOGR) on November 14, 2024 decided to make adjustments to the text of the Russian Consensus “Hyperammonemia in Adults” published in 2021 (Version 2021).