Genotype Distribution and Characteristics of Chronic Hepatitis C Infection in Estonia, Latvia, Lithuania, and Ukraine: The RESPOND-C Study.

Background and objectives: Since 2013, highly effective direct-acting antiviral (DAA) treatment for chronic hepatitis C (CHC) has become available, with cure rates exceeding 95%. For the choice of optimal CHC treatment, an assessment of the hepatitis C virus (HCV) genotype (GT) and liver fibrosis stage is necessary. Information about the distribution of these parameters among CHC patients in Estonia, Latvia, and Lithuania (the Baltic states) and especially in Ukraine is scarce. This study was performed to obtain epidemiologic data regarding CHC GT and fibrosis stage distribution for better planning of resources and prioritization of patients for DAA drug treatment according to disease severity in high-income (the Baltic states) and lower-middle-income (Ukraine) countries. Materials and methods: The retrospective RESPOND-C study included 1451 CHC patients. Demographic and disease information was collected from medical charts for each patient. Results: The most common suspected mode of viral transmission was blood transfusions (17.8%), followed by intravenous substance use (15.7%); however, in 50.9% of patients, the exact mode of transmission was not clarified. In Ukraine (18.4%) and Estonia (26%), transmission by intravenous substance use was higher than in Lithuania (5%) and Latvia (5.3%). Distribution of HCV GT among patients with CHC was as follows: GT1-66.4%; GT3-28.1; and GT2-4.1%. The prevalence of GT1 was the highest in Latvia (84%) and the lowest in Ukraine (63%, p < 0.001). Liver fibrosis stages were distributed as follows: F0-12.2%, F1-26.3%, F2-23.5%, F3-17.1%, and F4-20.9%. Cirrhosis (F4) was more prevalent in Lithuanian patients (30.1%) than in Estonians (8.1%, p < 0.001). Conclusions: This study contributes to the knowledge of epidemiologic characteristics of HCV infection in the Baltic states and Ukraine. The data regarding the patterns of HCV GT and fibrosis stage distribution will be helpful for the development of national strategies to control HCV infection in the era of DAA therapy.

ADDITIONAL RISKS ARISING IN THE PROCESS OF PROVIDING MEDICAL AID TO PATIENTS WITH COVID-19.

OBJECTIVE: The aim: In order to assess the degree of transforming danger, for face masks, used in the providing respiratory support process to specialized department patients with varying degrees of the COVID-19 course severity, we conducted a series of bacteriological studies into an additional opportunistic bacteria reservoir. With the purpose of assessment of the face respiratory masks inner surface bacterial contamination intensity during their use to provide respiratory support to patients with COVID-19. PATIENTS AND METHODS: Materials and methods: A bacteriological study of the inner surface of 60 disposable individual face respiratory masks was carried out at different times of providing respiratory support to patients with COVID-19. RESULTS: Results: It is shown that during use, the inner surface of the respiratory mask is colonized by staphylococci and gram-negative opportunistic bacteria. With increasing time of the mask using, the density of colonization of its inner surface increases. CONCLUSION: Conclusions: In the process of long-term non-invasive lung ventilation and oxygen therapy for patients with COVID-19, the inner surface of face respiratory masks is colonized with opportunistic bacteria, which creates the risk of contamination by the latter of the pathologically changed lung parenchyma and the addition of secondary bacterial infection.

Simeprevir with pegylated interferon alfa 2a plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-1): a phase 3, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Although the addition of the HCV NS3/4A protease inhibitors boceprevir and telaprevir to pegylated interferon (peginterferon) alfa plus ribavirin has improved sustained virological response (SVR) in treatment-naive and treatment-experienced patients infected with hepatitis C virus (HCV) genotype 1, the regimens have a high pill burden and are associated with increased rates and severity of adverse events, such as anaemia and rash. The efficacy and safety of the combination of simeprevir, a one pill, once-daily, oral HCV NS3/4A protease inhibitor, plus peginterferon alfa 2a plus ribavirin were assessed in treatment-naive patients with HCV genotype 1 infection. METHODS: In QUEST-1, a phase 3, randomised, double-blind multicentre trial undertaken in 13 countries (Australia, Europe, North America, Puerto Rico, and New Zealand), 394 patients (aged ≥18 years) with chronic HCV genotype 1 infection and no history of HCV treatment, stratified by HCV subtype and host IL28B genotype, were randomly assigned in a 2:1 ratio with a computer-generated allocation sequence to receive simeprevir (150 mg once daily, orally) plus peginterferon alfa 2a plus ribavirin for 12 weeks, followed by peginterferon alfa 2a plus ribavirin (simeprevir group), or placebo orally plus peginterferon alfa 2a plus ribavirin for 12 weeks, followed by peginterferon alfa 2a plus ribavirin (placebo group). Treatment duration was 24 weeks or 48 weeks in the simeprevir group according to criteria for response-guided therapy (ie, HCV RNA <25 IU/mL [undetectable or detectable] at week 4 and <25 IU/mL undetectable at week 12) and 48 weeks in the placebo group. Patients, study personnel, and the sponsor were masked to the treatment group assignment. The primary efficacy endpoint was sustained virological response 12 weeks after the planned end of treatment (SVR12) and was assessed with an intention-to-treat analysis. The results of the primary analysis (week 60) are presented for safety and SVR12. This trial is registered with ClinicalTrials.gov, number NCT01289782. FINDINGS: Treatment with simeprevir, peginterferon alfa 2a, and ribavirin was superior to placebo, peginterferon alfa 2a, and ribavirin (SVR12 in 210 [80%] patients of 264 vs 65 [50%] of 130, respectively, adjusted difference 29·3% [95% CI 20·1-38·6; p<0·0001). Adverse events in the first 12 weeks of treatment led to discontinuation of simeprevir in two (<1%) patients and discontinuation of placebo in one patient (<1%); fatigue (106 [40%] vs 49 [38%] patients, respectively) and headache (81 [31%] vs 48 [37%], respectively) were the most common adverse events. The prevalences of anaemia (42 [16%] vs 14 [11%], respectively) and rash (72 [27%] vs 33 [25%]) were similar in the simeprevir and placebo groups. Addition of simeprevir did not increase severity of patient-reported fatigue and functioning limitations, but shortened their duration. INTERPRETATION: Simeprevir once daily with peginterferon alfa 2a and ribavirin shortens therapy in treatment-naive patients with HCV genotype 1 infection without worsening the adverse event profiles associated with peginterferon alfa 2a plus ribavirin. FUNDING: Janssen Infectious Diseases-Diagnostics.

Prognostic influence of toll-like receptor 4 gene polymorphism into community-acquired pneumonia course among young patients with cytomegalovirus persistence.

OBJECTIVES: The aim of this study was to determine the predictive role of TLR4 polymorphism in CAP course among young cytomegalovirus-positive patients. SUBJECTS AND METHODS: One hundred and five patients with pneumonia (age range: 18-44 years) and 61 healthy respondents were observed clinically and specifically (by cytomegalovirus markers and TLR4 + 3725 G/C polymorphism). RESULTS: Among CAP patients, there were 51 male (48.6%) and 54 female (51.4%), with average age 34.1 ± 0.8 years, and there were 19 (18.1%) patients with Pneumonia Patient Outcomes Research Team (PORT) I, 46 (43.8%) patients with PORT II, 31 (29.5%) patients with PORT III, and 9 (8.6%) patients with PORT IV. Cytomegalovirus persistence was detected in 80 (48.2%) patients and 34 (20.5%) healthy respondents (P = 0.003). G/G genotype of TLR4 signaling was found in 78 (74%) patients with pneumonia, G/C in 24 (23%) patients, and C/C in 3 (3%) patients. Among G/C patients, there were 16.2% cytomegalovirus-positive patients versus 6.7% negative patients (P < 0.05), as well as among G/G patients, and there were 59% versus 15,2%, accordingly (P < 0.01). The patients of the main group with G/G genotype were characterized by mostly mild (PORT I - 15 [14.3%]) and moderate pneumonia severity (PORT II - 32 [30.5%] and PORT III - 26 [24.8%] patients). The patients with G/C genotype were characterized by mostly PORT II (11 [10.5%] patients). All C/C genotype patients have PORT II (P < 0.05). CONCLUSIONS: Cytomegalovirus persistence worsens the pneumonia course. G/G and G/C TLR4 genotypes are associated with mild pneumonia severity.