Objective. To perform a comparative analysis of clinical and food isolates of Listeria monocytogenes collected in the European part of Russia in 2018–2019. Materials and Methods. We used multilocus sequencing (MLST), supplemented by virulence loci, including fragments of internalin genes (MvLST, Multi-virulent-locus sequence typing), followed by phylogenetic analysis. Results. The main diagnoses for clinical isolates were prenatal and neonatal listeriosis and meningitis. Clinical isolates predominantly belonged to phylogenetic line II with the predominance of ST7, which was also the most abundant in food isolates. The second most common occurrence in food isolates was ST121, widely distributed in Europe. Isolates of phylogenetic line I in the group of clinical cultures in three cases were represented by ST6, detected during outbreaks of listeriosis in Europe 2015–2018 and South Africa in 2017–2018. Only in one isolate from food belonged to the phylogenetic lineage I. In general, the diversity of food isolate genotypes was significantly higher than clinical isolates. The analysis of virulence loci revealed a new internalin A allele and a new internalin genes profile (IP) in isolate ST7 from food. Conclusions. L. monocytogenes of the most common ST7 is autochthonous in Russia; cases of listeriosis caused by the ST6 bacterium are most likely imported. Based on the analysis of the diversity of ST and IP of L. monocytogenes identified in Russia, a rapid diagnosis scheme for epidemiological investigation is proposed.

The aim of the study was to identify the most effective serum tumor markers for early diagnosis of hepatocellular carcinoma based on the combination of diagnostic characteristics and correlations. Materials and Methods. There were observed 55 patients with chronic hepatitis C in the stage of liver cirrhosis with a verified diagnosis of hepatocellular carcinoma. The control group consisted of 55 patients with chronic hepatitis C at the stage of liver cirrhosis without hepatocellular carcinoma, comparable to the experimental group in terms of basic clinical profile. The following tumor markers were estimated in both groups: alpha-fetoprotein (AFP), alpha-fetoprotein-L3 (AFP-L3), annexin A2 (ANXA2), heparin-binding growth factor Midkine (MDK), glypican-3 (GPC3), des-gamma-carboxyprothrombin (DCP, PIVKA-II), dickkopf-related protein 1 (DKK-1), osteopontin (OPN), and Golgi protein 73 (GP73). There were also evaluated such indices as diagnostic sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio of a positive test, the possible correlation between alpha-fetoprotein and other tumor markers. The area under the ROC curve (AUC) was calculated at the 95% confidence interval. Results. The greatest sensitivity was revealed when using heparin-binding growth factor, annexin A2, osteopontin. Alpha-fetoprotein, alpha-fetoprotein-L3, glypican-3, des-gamma-carboxyprothrombin, dickkopf-related protein 1 had the best specificity. AUC>0.75 was found in annexin A2, heparin-binding growth factor, glypican-3, des-gamma-carboxyprothrombin, osteopontin, Golgi protein 73. The likelihood ratio of a positive test result was the highest for glypican-3. A significant correlation was found between alpha-fetoprotein and alphafetoprotein-L3, annexin A2, des-gamma-carboxyprothrombin. Conclusion. According to the aggregate indicators of diagnostic efficiency, heparin-binding growth factor, glypican-3, and osteopontin are the most promising tumor markers of those studied. When they are used, integral AUC values are above the average, the level of these tumor markers in the blood of patients with hepatocellular cancer does not correlate with alpha-fetoprotein. They are applicable for diagnosing liver cancer in AFP-negative patients. The combined use of AFP + GPC3, AFP + OPN has already shown their advantages. However, the efficacy of the combination of AFP + MDK, GPC3 + OPN has not been determined yet; therefore, significance of the combined use of these tumor markers in the diagnosis of liver cancer should be investigated in the near future.

BACKGROUND: The poor outcomes of chronic hepatitis C (CHC) and type 2 diabetes determine the socio-economic significance of the combined pathology since they lead to premature death. The proportion of patients with type 2 diabetes with markers of viral hepatitis (VH) in the Russian Federation is not known, which does not allow us to estimate the burden for the state of this medical problem.OBJECTIVE: Assessment of the prevalence of concomitant pathology, HCV infection and type 2 diabetes, as well as the proportion of severe liver damage in its structure, according to the analysis of the primary medical records of four Moscow hospitals.MATERIALS AND METHODS: A retrospective analysis of the medical records of patients with HCV infection and diabetes mellitus, who admitted at different periods to four hospitals in Moscow, was carried out, as well as a total examination for the presence of anti-HCV in the blood of all patients with diabetes who were admitted within a certain period to the endocrinology department of a multidisciplinary hospital. Additionally, to determine the proportion of patients with liver cirrhosis (LC), an additional examination of patients with this combined pathology was carried out in accordance with the standards for the diagnosis of hepatitis C.RESULTS: In total, according to data from 4 hospitals in Moscow, over a certain period, 2% (105/5298) of diabetes patients with anti-HCV in their blood were identified. Sex ratio for men: women = 54 (51%): 51 (49%). Patients aged 50–69 years prevailed — 70% (74/105). Seroprevalence of HCV in cohorts of patients with type 2 diabetes according to the analysis in 3 health facilities: 0.9% (20/2196), 1.9% (8/432), 1.9% (28/1500). A significant drawback was revealed that did not allow assessing the true seroprevalence of HCV: not all patients were hospitalized with the results of a VH test, and not all of them were assigned an examination for VH markers if it was not performed before hospitalization. The proportion of type 2 diabetes patients with anti-HCV in the blood according to the results of total screening (3.7%; 16/432) became comparable to the proportion of type 2 diabetes patients among patients with CHC admitted to an infectious hospital (4.2%; 49 / 1170). The proportion of patients with LC according to the analysis of the medical records of the infectious hospital is 65% (32/49), in the group of endocrinological patients with additional examination it is 18% (13/71).CONCLUSION: For the first time in the Russian Federation, data were obtained on the prevalence of HCV infection in combination with type 2 diabetes. The results of the study indicate the need to develop effective screening programs to detect active HCV infection in the group of patients with diabetes, as well as patients among them with severe hepatic fibrosis for the timely conduct of highly effective antiviral therapy, which will prevent poor outcomes in a separate perspective.

Hepatocellular carcinoma (HCC) is the second leading cause of death in oncological patients. The prognosis of the disease outcome depends directly on its timely detection. Currently, in the majority of countries, the diagnostic algorithm at the preclinical stage of tumor development includes determination of alpha-fetoprotein in combination with instrumental imaging techniques. This approach allows the detection of about 65-80% of liver tumors at an early stage (A according to the BCLC classification), whereas at a very early stage (0 according to the BCLC classification) only 32-50% of cases, the result which cannot be considered satisfactory. In this regard, the search for effective biomarkers of hepatocellular carcinoma is an important challenge that faces the world healthcare. Advances in proteomics and genomics have led to the discovery of numerous promising markers which are now being clinically tested. Molecules of protein nature proposed as hepatocellular carcinoma tumor markers in different periods of time are described in this review. Comparative data on their effectiveness and specificity are also presented. The possibility of isolated or combined use of these biomarkers for risk assessment and early diagnosis of primary liver cancer is considered.

Aim. To establish the main external and genetically determined risk factors for the development of hepatocellular cancer in the ethnic group of male Yakuts living in the Republic of Sakha (Yakutia) [RS (Y)] in the epidemiologically unfavorable conditions of the incidence of viral hepatitis. Materials and methods. A total of 97 male Yakuts were examined, including 44 people diagnosed with hepatocellular cancer and 53 people diagnosed with chronic viral hepatitis. HCC risk factors were identified by analyzing medical records and questioning patients. In the experimental and control groups, genetic studies of single nucleotide polymorphisms of genes mapped on the X-chromosome and involved in the activation of antiviral immunity along the TLR7 signaling pathway were performed. Results and discussion. In 100% of patients with hepatocellular cancer, infection with hepatitis B, C, D viruses or co - infection with these agents was detected. Every fourth patient with HCC in the RS (Y) was infected with hepatitis D. The course of hepatocellular cancer associated with HDV was characterized by rapid progression of liver cirrhosis, development of portal hypertension, bleeding from varicose veins of the stomach and esophagus (36.4%) and edematous ascitic syndrome (63.6%). In addition to viral agents, additional risk factors for liver cancer were identified, such as alcohol abuse, overweight, diabetes mellitus, and smoking. Among the studied variation sites of genes localized on the X-chromosome and encoding the reaction of innate antiviral immunity, no genetic marker was found with a sufficient degree of confidence determining the likelihood of hepatocellular cancer developing. Conclusions. The high incidence of hepatocellular carcinoma of the male population in the RS (Y) is due to the widespread prevalence of parenteral viral hepatitis, especially viral hepatitis D. Due to the introduction of mass vaccination of the population against hepatitis B in the Russian Federation in the foreseeable future in the RS (Y) we should see a decrease in the proportion of hepatocellular cancer associated with hepatitis B and D viruses, and therefore the focus should be on the treatment and prevention of hepatitis C virus and non - infectious risk factors.

Заключение. Вероятность развития листериозного сепсиса и/или менингита/менингоэнцефалита на фоне тяжелого течения COVID-19 и высокий риск неблагоприятного исхода требуют повышения осведомленности медицинских работников в области диагностики и лечения инвазивного листериоза для проведения максимально ранней и адекватной антибактериальной терапии.Финансирование. Исследование не имело спонсорской поддержки. Конфликт интересов. Авторы заявляют об отсутствии конфликта интересов.

Aim. Evaluate efficacy and safety of a combination of direct - acting antivirals narlaprevir/ritonavir with daclatasvir in patients with viral hepatitis C. Materials and methods. The study enrolled adult patients with HCV genotype 1b infection without demonstrated NS5A resistance - associated substitutions Y93C/H/N/S and/or L31F/M/V/I. Patients were treated with narlaprevir 200 mg QD, ritonavir 100 mg QD and daclatasvir 60 mg QD. Treatment duration was 12 weeks. Proportion of patients achieving sustained virological response 12 weeks after treatment (SVR12) was the primary efficacy endpoint. Results and discussion. In total, 105 (75.0%) patients were treatment with the study combination. Patients’ age varied from 21 to 69 years, the mean age being 43.2±10.9 years. There were slightly more women (55.2%), and 69 patients (65.7%) had comorbidities. SVR 12 was 89.5% (95% CI 82.0-94.7%). In 10 of 11 patients with treatment failures NS5A resistance - associated substitutions in residues 31 and/or 93 were found, as well as less clinically relevant substitutions L28M, P58S, R30Q, Q62K. Adverse events (AEs) were found in less than one half of patients (45 patients, or 42.9% in the safety population). Almost all recorded AEs were mild to moderate. Conclusion. Efficacy of treatment with a combination of narlaprevir/ritonavir and daclatasvir in treatment - naïve patients with HCV genotype 1b was close to 90%. This combination was found to be safe and well - tolerated.

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