[Use of a combination of the virus-neutralizing monoclonal antibodies casirivimab and imdevimab for mild to moderate COVID-19 in patients at high risk of progression: Results of the non-interventional observational study].

AIM: To evaluate the efficacy and safety of a combination of virus-neutralizing monoclonal antibodies - MAB (casirivimab and imdevimab) in patients with mild to moderate COVID-19 with risk factors in real word settings. MATERIALS AND METHODS: A non-interventional non-comparative observational study with primary prospective data collection included 108 patients with mild to moderate COVID-19 (mean age 61 years), who had risk factors for developing severe disease. All patients (n=108) were treated with a combination of MAB casirivimab and imdevimab intravenous single infusion 1200 mg (600 mg of each component). The efficacy and safety of MAB were assessed at 7, 14, and 28 days after infusion. RESULTS: Efficacy. Indications for hospitalization by day 7 from the moment of MAB administration were in 0.9% (n=1), by day 14 - in 1.9% (n=2), by day 28 - in 0.9% of patients; to stay in the intensive care units by the 7th day - in 4.6% (n=5), by the 14th day - in 0.9% (n=1), by the 28th day - in 0.9% (n=1) patients. During 28 days of follow up, the need for mechanical ventilation and extracorporeal membrane oxygenation was registered in 2/108 (1.8%) patients. There were no deaths directly related to COVID-19 in the assessed cohort of patients. Safety. By the 28th day of the follow up, no adverse effects due to MAB therapy were registered. CONCLUSION: An analysis of the results of a non-interventional observational study summarized in this article showed the high efficacy and safety of virus-neutralizing MAB combination (casirivimab and imdevimab) in patients with mild to moderate COVID-19 with of risk factors for severe COVID-19 in real word settings.

[Effectiveness of empirical Helicobacter pylori eradication therapy with furazolidone in Russia: results from the European Registry on Helicobacter pylori Management (Hp-EuReg)].

BACKGROUND: First-line therapy does not always provide a high level of Helicobacter pylori eradication due to the increase of H. pylori resistance to antibiotics; therefore, it remains necessary to identify the most effective rescue treatments. The purpose of this study was to evaluate the efficacy and safety of empirical H. pylori furazolidone-containing regimens. MATERIALS AND METHODS: Adult H. pylori infected patients empirically treated with furazolidone-containing eradication regimens were registered in an international, prospective, multicenter non-intervention European registry on H. pylori management (Hp-EuReg). Data were collected at AEG-REDCap e-CRF from 2013 to 2021 and the quality was reviewed. Modified intention-to-treat (mITT) effectiveness analyses were performed. RESULTS: Overall 106 patients received empirical furazolidone-containing therapy in Russia. Furazolidone was prescribed in a sequential scheme along with amoxicillin, clarithromycin and a proton pump inhibitor in 68 (64%) cases, triple regimens were prescribed in 28 (26%) patients and quadruple regimens in 10 (9.4%). Treatment duration of 7 days was assigned to 2 (1.9%) patients, 10-day eradication therapy in case of 80 (75%) and 14 days - in 24 (23%) patients. Furazolidone was mainly used in first- (79%) and second-line (21%) regimens. The methods used to diagnose H. pylori infection were: histology (81%), stool antigen test (64%), 13C-urea breath test (6.6%), and rapid urease test (1.9%). The mITT effectiveness of sequential therapy was 100%; 93% with the triple therapy and 75.5% with quadruple therapy. Compliance was reported in 98% of cases. Adverse events were revealed in 5.7% of patients, mostly nausea (3.8%). No serious adverse events were reported. CONCLUSION: Furazolidone containing eradication regimens appear to be an effective and safe empirical therapy in Russia.

Generation of an induced pluripotent stem cell line ICGi030-A from a Wilson's disease patient carrying a frameshift mutation p.Lys1013fs and missense mutation p.H1069Q in the ATP7B gene.

Wilson's disease is a rare autosomal recessive disorder of copper metabolism. The copper accumulation in the viscera appears due to the functional impairment of copper-transporting ATPase, which is encoded by the ATP7B gene. In this study, PBMCs of a patient with two ATP7B mutations were reprogrammed. The first mutation is a missense mutation p.H1069Q, which is the most frequent mutation in the human population. At the same time, the second one is a frameshift mutation p.Lys1013fs. The generated iPSC line had a normal karyotype, maintained the original genotype, expressed pluripotency markers, and demonstrated the ability to differentiate into derivatives of the three germ layers.

[Efficacy and safety of bulevirtide in patients with chronic hepatitis D and compensated cirrhosis].

AIM: To study the efficacy and safety of bulevirtide, the HBV and HDV entry inhibitor. MATERIALS AND METHODS: Analysis of the results of using bulevirtide in randomized controlled open-label comparative studies MYR202 and MYR203 in 56 patients with chronic hepatitis D and compensated cirrhosis, in monotherapy and combination with pegylated interferon alpha-2a (PEG-IFN). RESULTS: Monotherapy with bulevirtide for 24 weeks in the MYR202 study in 46 patients with compensated liver cirrhosis demonstrated: 1) a high rate of virological (100%) and biochemical response (alanine aminotransferase normalization rate 45.7%), 2) superiority of bulevirtide in efficacy over the control group (tenofovir), 3) comparability of treatment efficacy in patients with and without cirrhosis, 4) no progression of liver fibrosis with elastometry in most patients. Treatment with bulevirtide in monotherapy and combination with PEG-IFN for 48 weeks in 10 patients with compensated liver cirrhosis in the MYR203 study was accompanied by a high rate of virological response (80%) and normalization of alanine aminotransferase (70%). Bulevirtide was well tolerated, there was no deterioration in tolerability compared with patients without cirrhosis, there were no serious adverse events and cases of treatment cancellation due to adverse events. CONCLUSION: Bulevirtide is recommended as the first line of treatment for chronic hepatitis D in patients with compensated cirrhosis in monotherapy and combination with PEG-IFN.

Generation of two induced pluripotent stem cell lines from peripheral blood mononuclear cells of a patient with Wilson's disease.

Wilson's disease is an inherited disorder associated with copper accumulation in the liver, brain and other vital organs. Wilson's disease is caused by mutations in the ATP7B gene. Over 300 mutations of ATP7B have been described. Despite the disease is autosomal recessive, the patient whose PBMCs were reprogrammed in the study harbours heterozygous mutation c.3207C > A (p.H1069Q). Detailed analysis of the ATP7B complete gene sequencing data has not revealed other known disease associated mutation. The generated iPSC lines maintained the original genotype, expressed pluripotency markers, had normal karyotype and demonstrated the ability to differentiate into derivatives of the three germ layers.

Possibilities of therapeutic correction of hyperammonemia and minimal hepatic encephalopathy in patients with chronic hepatitis C at the pre-cirrhotic stage.

AIM: Study of the social consequences of cognitive disorders in minimal hepatic encephalopathy (MHE) in patients with chronic genotype 1 hepatitis C and the possibilities of their pharmacological correction with L-ornithine-L-aspartate (LOLA, Hepa-Merz). MATERIALS AND METHODS: The study group included 60 male patients diagnosed with chronic hepatitis C, genotype 1 with fibrosis stage F1 according to the METAVIR scale, and presented with MHE. The average age of the patients was 34.2±5.3 years. The control group included 20 healthy men aged 34.1±5.8 years without liver disease. Intermittent treatment with LOLA was given to the study group at 15 g once daily in the morning for 2 months with 2-month off-treatment intervals, with the total treatment duration of 12 months. In the course of treatment, MHE dynamics was assessed using the critical flicker fusion frequency (CFF) test and the number connecting test (NCT), as well as by serum concentrations of ammonium ion. The LOLA efficacy endpoint was the change in the frequency of violations of traffic rules (traffic code). RESULTS: A significant decrease in the concentration of ammonium ion was observed after 5 months of treatment (135.53 and 82.9 µmol/L, p=0.002) and maintained throughout the study. The results of the CFF test significantly improved by the end of the 1st month of LOLA treatment (p=0.008), remaining at the achieved level for 9 months. The NCT parameters reached their minimum values after 5 months (p<0.001) and remained at this level throughout the study. During the study period, the frequency of traffic code violations by participants decreased from 60 to 40% (р=0.03). CONCLUSION: Fractional treatment with LOLA leads to a decrease in the blood concentration of ammonium ion and, consequently, to an improvement in psychometric test results and a decrease in the frequency of traffic code violations. The result achieved can have an impact on the accident rate reduction.

[Some practical issues in the management of patients with decompensated liver cirrhosis].

The natural course of cirrhosis is characterized by a shift from a compensated stage without clinical manifestations to a subsequent decompensated stage, which is characterized by the development of obvious clinical symptoms, the most frequent of which are ascites, bleeding from varicose veins, bacterial infections, encephalopathy. The articles and reviews of recent years emphasize the importance of etiotropic treatment of liver cirrhosis at any stage, including the final one. In addition, pathogenetic and symptomatic therapy aimed at treating complications of cirrhosis of the liver: ascites, dilution hyponatremia, gastrointestinal bleeding, bacterial infections, and kidney damage comes to the forefront at the stage of decompensation, which allows the patient to be on the waiting list for liver transplantation. This category of patients, as a rule, is difficult to treat and has features and subtleties of reference.

[Predictors of the efficiency of short-term interferon-containing therapy using direct-acting antiviral drugs in patients with chronic hepatitis C virus genotype 1]. / Prediktory éffektivnosti korotkogo kursa interferonsoderzhashchei terapii s primeneniem preparatov priamogo protivovirusnogo deistviia u patsientov s khronicheskim gepatitom, vyzvannym virusom gepatita S 1-go genotipa.

AIM: To identify predictors for the high efficiency of short-term interferon-containing antiviral therapy (AVT) using direct-acting antivirals (DAAs) in patients with chronic hepatitis C (CHC) virus (HCV) type 1 (CHC-1). MATERIAL AND METHODS: A total of 2,798 case histories of patients aged 18 to 60 years who received AVT using peginterferon, ribavirin in combination with DAAs for CHC-1, which was stopped at 10 to 14 weeks, were selected from the archives of the healthcare facilities of the Moscow Region. The inclusion criteria were aviremia achieved when AVT was discontinued; therapy using the dose recommended in compliance with the international standards; and adherence during treatment. RESULTS: The analysis included 179 case histories, including 158 cases of discontinuation of triple AVT using a protease inhibitor (telaprevir) and 22 cases of that of quadruple treatment (QT) with asunaprevir and daclatasvir. There were two main factors predicting a high probability of achieving a sustained virological response (SVR) in patients with HCV-1 during short-term triple AVT: viremia at 28 days of AVT, which was registered by a highly sensitive polymerase chain reaction (PCR) assay (its analytical sensitivity was 12 IU/ml), and the genotype CC of interleukin-28B (IL-28B) rs12979860. With a combination of these two factors, recovery was observed in 100% of cases. SVR was observed in all cases of QT discontinuation, regardless of the stage of fibrosis and the subtype of CHC genotype. However, the resulting sample was unrepresentative. CONCLUSION: Triple AVT using a protease inhibitor may be reduced in patients with CHC-1 and the CC allelic variant in IL-28B if viremia is achieved at 28 days of AVT, as evidenced by highly sensitive PCR assay. Short-term QT needs further investigation.

[Nonalcoholic fatty liver disease without obesity: the problem to be solved]. / Nealkogol'naia zhirovaia bolezn' pecheni bez ozhireniia: problema, ozhidaiushchaia resheniia.

It is generally agreed that nonalcoholic fatty liver disease (NAFLD) is a component of metabolic syndrome and is frequently associated with obesity, type 2 diabetes mellitus, atherogenic dyslipidemia, and other components of the syndrome. However, there is no doubt that not all overweight people develop NAFLD and, conversely, the latter may be present in normal weight individuals. The prevalence of NAFLD without obesity in different countries is very variable from 3 to 30%. Its risk factors are considered to be both exogenous (for example, excess intakes of cholesterol and rapidly assimilable fructose) and genetically determined (allelic variants of the genes encoding adiponutrin, the cholesteryl ester transport protein, sterol-regulatory element-binding protein 2). The methods for the diagnosis of NAFLD without obesity do not differ in essence from those for classic NAFLD. Analysis of the conducted investigations gives grounds to claim that lifestyle modification as exercises and dietary restrictions improves biochemical parameters and histological pattern. The efficiency of drug treatments needs further investigation.

[Hepatitis virus genotype structure in patients with chronic hepatitis C].

AIM: Studies of hepatitis C virus (HCV) genotype and subtype structure in patients with chronic hepatitis C in 3 regions of the Central federal district of Russia. MATERIALS AND METHODS: Hepatitis C virus genotype and subtype structure was determined in patients with chronic HCV infection in Moscow (1993 - 1995 and 2005), Moscow region (2008) and Vladimir region (1993 -1995, 2005-2007). HCV genotype was determined by using A. Widell et al. (1994) technique, PCR (AmpliSens diagnostic kits), Genotype C test system. RESULTS: In all studied regions and during all the time periods the first position in rating belonged to HCV 1b subtype. In 1993 - 1995 and 2005 - 2007 period changes in HCV genotype and subtype structure were registered that consisted of relative weight of 1b subtype decrease and 3a subtype increase. Subtype 1b in females with chronic hepatitis C was registered more often than in males. In Vladimir region 3a subtype in males was detected more often than in females. In males older than 30 years the first rating position belongs to 1b subtype and in males younger than 30 years--subtype 3a. In females older than 30 years in Moscow region and Vladimir region, as well as in females younger than 30 years in Vladimir region subtype 1b was detected more often, while in Moscow region HCV subtypes 1b and 3a were detected with the same rate of 47.6%. CONCLUSION: Currently there is an urgent need to include mandatory monitoring of hepatitis C virus genetic variants into the system of hepatitis C epidemiologic control in Russia. This approach will allow for a significant increase in quality of hepatitis C serological diagnostics, and can be used in the prognosis of evolution of the epidemic process of this disease.

[Effectiveness of lamivudine in the treatment of chronic HBeAg-negative viral hepatitis B: results of continuous therapy for 18 months]. / Effektivnost' lamivudina v lechenii HBeAg-negativnogo khronicheskogo virusnogo gepatita B: rezul'taty nepreryvnoi terapii v techenie 18 mes.

The efficacy of monotherapy with one of the analogues of synthetic nucleosides (lamivudine) was studied in 22 patients with chronic viral hepatitis B (CVHB). The specific feature of the selected group was that there was no serum HBeAg, which is usually regarded as a sign of viral mutation. The time course of changes in the activity of blood and hepatic inflammatory processes and viral replication were studied at equal intervals. There was a direct correlation between the suppression of viral replication and the regression of activity indices, such as ALT, serological markers, DNA of viral hepatitis B, and the morphological constituents of the Knodell index) during lamivudine therapy. However, there were no substantial changes in the parameters of fibrosis throughout the treatment. Therapy resistance was revealed in 3 of the 22 patients with CVHV. Its basis was the mutation of hepatitis B virus in the YMDD-motive, which was detected in 2 of the 3 patients.

[Comparative study of chromatography-mass spectrography of microorganism's chemical markers in blood and intestinal mucosa bioptats]. / Sravnitel'noe khromato-mass-spektrometricheskoe issledovanie sostava khimicheskikh markerov mikroorganizmov v krovi i bioptatakh slizistoi obolochki kishechnika.

Fatty acids, that are microorganism's markers in blood and jejunum's, ileum's, and large intestine's bioptats of the patients with irritable bowel syndrome were investigated with gas chromatography. Markers of Cl. perfringens, Cl. difficile, Enterococcus, Streptomyces, Enterobacterial, Klebsiella, E. coli, Peptostreptococcus, Candida Albicans, genus of Streptococcus, of Staphylococcus, of Fusobacterium sp and others microorganisms were revealed. Settling of intestinal mucosa was the same in jejunum, ileum and large intestine (0.5-1.3) x 10(10) cells/gr. and was approximately the same as microorganism's concentration in feces (1.8 x 10(11) cells/gr). Correlation of blood and bioptats markers was demonstrated in the most patients. The possibility to use specific fatty blood acids as microorganisms markers in preliminary diagnosis of mucosa microflora changes is discussed.