[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.

[Assessment of external risk factors of hepatocellular cancer development and markers of genetic predisposition to its development in the ethnic group of yakut - men].

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.

[Experience of olokizumab use in COVID-19 patients].

Most subjects with the COVID-19 experience mild to moderate symptoms, but approximately 10% of cases suffer from severe course of disease. IL-6 inhibitors are actively used to neutralize and prevent the cytokine storm. Olokizumab is a humanized monoclonal antibody belonging to the G4/Kappa immunoglobulin isotype that selectively binds to human IL-6 and effectively neutralizes it. AIM: To evaluate the efficacy and safety of Artlegia (olokizumab) for the treatment of subjects with a disease caused by the SARS-COV-2 virus in a real-world clinical setting. MATERIALS AND METHODS: The analysis included data of 610 subjects aged 55.0812.68 years who received olokizumab at a single dose of 160 mg/mL 0.4 mL subcutaneously as a preemptive anti-inflammatory therapy. The comparison group included 511 subjects aged 55.2311.23 years who received standard therapy without IL-6 inhibitors. Control Endpoints: 1. Positive clinical changes on Day 7. 2. Changes in the CRP levels on Days 1, 2, and 7. 3. Duration of oxygen therapy. 4. Number of days in hospital. 5. Number of adverse events. 6. Disease outcome. RESULTS: If a cytokine storm occurs, immune regulatory events will trigger the development of either a protective immune response or an exacerbated inflammatory response. The use of preemptive anti-inflammatory therapy has both a short-term and, most importantly, a long-term effect on the T and B parts of the immune process. These aspects definitely require further research and observation. CONCLUSION: The use of olokizumab to treat the new COVID-19 coronavirus disease has demonstrated a positive effect on clinical and laboratory parameters. Primarily, it affects the severity of clinical parameters by improving the general condition already on the first day of observation, and decreasing body temperature to normal values. The changes in the C-reactive protein levels show a significant effect of the IL-6 inhibitor on the systemic inflammatory response.

THE ROLE OF VIRAL HEPATITIS IN THE MECHANISM OF LIVER CANCER FORMATION AMONG THE FAR NORTH INDIGENOUS INHABITANTS.

INTRODUCTION: Yakutia is a region of high prevalence of viral hepatitis B, C and D. The rating and ranking of risk factors for the formation of cirrhosis and primary liver cancer in patients with chronic viral hepatitis (CVH) B, C and D in the Republic of Sakha (Yakutia) (R S(Y)), it is a serious medical problem. AIM: Studying of the main reasons for the progression of chronic viral hepatitis B, C and D to cirrhosis and liver cancer in the Far North. MATERIALS AND METHODS: Materials of official statistics of theTerritorial Rospotrebnadzor and official registration of the Ministry of Health of RS (Y); serological and molecular biological research methods to the studying of HCV genotype B, C, D. RESULTS: On the basis of long-term morbidity of chronic viral hepatitis B, C and D and their outcomes in Yakutia defined a role in the progression to cirrhosis and primary liver cancer, ethnicity and genotype of HBV and HDV. Established fact of viral replication in cirrhosis and primary liver cancer under adverse social and environmental factors, genetically determined increased concentration of acetaldehyde due to impaired activity of alcohol dehydrogenases (ADH) and aldegiddegirogenases (AIDG) at the indigenous inhabitants of the republic proves the need for targeted therapy of complex events. CONCLUSIONS: The regions of Yakutia are the most affected by the virus of hepatitis B, C and D with progressive course of the disease to cirrhosis and cirrhosis liver cancer, defined by genotype hepatitis B & D, in which significantly usually occurs primary liver cancer, also noted that the combined mixed-replicating virus hepatitis is a risk factor for primary liver cancer.

BREADTH SPREADING OF VIRAL HEPATITIS MARKERS IN THE RISK GROUPS IN THE REPUBLIC OF SAKHA (YAKUTIA).

INTRODUCTION: Republic of Sakha (Yakutia) is a hyperendemic region of Russian Federation for spreading of parenteral viral hepatitis B, C and D. In risk groups of these diseases are firstly medical personnel, who contacting with infection carriers including latent infections family and members of families of chronic viral hepatitis carriers. AIM: To reveal the breadth of spreading of viral hepatitis markers in the risk groups. MATERIALS AND METHODS: The level of HBV- and HC- infection were determined in medical staff of large multi specialty hospital and family members of people with viral hepatitis B and C. Epidemiological, clinical, serological and molecular biology methods of viral hepatitis diagnostics were applied in this study. RESULTS: Results of this study showed that the staff at surgery and hematology departments and all nursing staff belong to the high-risk of HBV-infection groups. Therefore, they are a priority for active immunization. Attention is paid on the fact that infectivity of medical staff is not equally distributed in dependence on type of department and position of medical staff. Rate HBV-marker detecting in "family hearths" was dependent on degree of interrelationship with infection source. According received information, in families of patientwith chronic hepatitis B spreading of infection was higher (77.6%) then in families of patients with acute hepatitis B (39.7%). At primary examination of families an anti-HCV was detected in 9.3 ± 1.8% cases, i.e. the spreading of HCV was at low-activity. CONCLUSIONS: Results of our study on spreading of hepatitis B and C in Yakutia showed the high rate of appearance of HCV and HBV markers in the risk groups.