Hepatitis C Virus Research Articles

Changes in hepatic steatosis before and after direct acting antiviral treatment in people living with HIV and Hepatitis C coinfection.

Both HIV and hepatitis C virus (HCV) infection increase the risk of hepatic steatosis (HS), which in turn contributes to the severity and progression of liver disease. Direct acting antivirals (DAAs) can cure HCV but whether they reduce HS is unclear. HS was assessed using the controlled attenuation parameter (CAP) and the hepatic steatosis index (HSI) in participants coinfected with HIV-HCV from the Canadian Coinfection Cohort. Changes in HS, before, during and after successful DAA treatment, were estimated using generalized additive mixed models, adjusted for covariates measured prior to treatment (age, sex, duration of HCV infection, body mass index, diabetes, prior exposure to dideoxynucleosides and hazardous drinking). 431 participants with at least one measure of CAP or HSI before treatment were included. CAP steadily increased over time: adjusted annual slope 3.3 dB/m (95% credible interval (CrI) 1.6, 4.9) before, and 3.9 dB/m (95% CrI: 1.9, 5.9) after DAA treatment, irrespective of pre-treatment CAP. In contrast, HSI changed little over time: annual slope 0.2 (95% CrI: -0.1, 0.5) before and 0.2 (95% CrI -0.1, 0.5) after, but demonstrated a marked reduction during treatment -4.5 (95% CrI -5.9, -3.1). When assessed by CAP, HS was unaffected by DAA treatment and steadily increased over time. In contrast, HSI did not appear to reflect changes in HS, with the decrease during treatment likely related to resolution of hepatic inflammation. Ongoing HS may pose a risk for liver disease in coinfected people cured of HCV.

Activation-Induced Marker Assay to Identify and Isolate HCV-Specific T Cells for Single-Cell RNA-Seq Analysis.

Identification and isolation of antigen-specific T cells for downstream transcriptomic analysis is key for various immunological studies. Traditional methods using major histocompatibility complex (MHC) multimers are limited by the number of predefined immunodominant epitopes and MHC matching of the study subjects. Activation-induced markers (AIM) enable highly sensitive detection of rare antigen-specific T cells irrespective of the availability of MHC multimers. Herein, we have developed an AIM assay for the detection, sorting and subsequent single-cell RNA sequencing (scRNA-seq) analysis of hepatitis C virus (HCV)-specific T cells. We examined different combinations of the activation markers CD69, CD40L, OX40, and 4-1BB at 6, 9, 18 and 24 h post stimulation with HCV peptide pools. AIM+ CD4 T cells exhibited upregulation of CD69 and CD40L as early as 6 h post-stimulation, while OX40 and 4-1BB expression was delayed until 18 h. AIM+ CD8 T cells were characterized by the coexpression of CD69 and 4-1BB at 18 h, while the expression of CD40L and OX40 remained low throughout the stimulation period. AIM+ CD4 and CD8 T cells were successfully sorted and processed for scRNA-seq analysis examining gene expression and T cell receptor (TCR) usage. scRNA-seq analysis from this one subject revealed that AIM+ CD4 T (CD69+ CD40L+) cells predominantly represented Tfh, Th1, and Th17 profiles, whereas AIM+ CD8 T (CD69+ 4-1BB+) cells primarily exhibited effector and effector memory profiles. TCR analysis identified 1023 and 160 unique clonotypes within AIM+ CD4 and CD8 T cells, respectively. In conclusion, this approach offers highly sensitive detection of HCV-specific T cells that can be applied for cohort studies, thus facilitating the identification of specific gene signatures associated with infection outcome and vaccination.

Seropositivity of hepatitis A and E viruses in patients attending a tertiary care center in central India

Objectives: Hepatitis A virus (HAV) and hepatitis E virus (HEV) infections are significant global health concerns that contribute to acute viral hepatitis. This study aimed to investigate the prevalence of HAV, HEV, and co-infections in a tertiary care hospital setting in central India. Materials and Methods: This retrospective observational study analyzed 987 clinical specimens collected from suspected acute viral hepatitis cases over 5 years (2019–2023). Commercially available enzyme-linked immunosorbent assay kits were used to detect HAV and HEV immunoglobulin M antibodies. Statistical analysis: Demographic data and clinical information were collected and analyzed using Chi-square tests. P < 0.05 was considered statistically significant, indicating a significant association between the variables under investigation. Results: Overall, 32.72% of patients were seropositive for either HAV, HEV, or both. The prevalence of HAV was 22.9%, HEV was 9.83%, and co-infection was 3.24%. HAV infection was more prevalent in children (0–14 years), whereas HEV was more prevalent in adults. Both HAV and HEV infections were associated with elevated liver function markers, with the highest levels observed in co-infected cases. The monsoon season had the highest number of cases. Conclusions: This study revealed a substantial burden of HAV, HEV, and co-infections in central India. The observed sex—and age-specific prevalence patterns warrant further investigation. Effective public health strategies addressing sanitation, hygiene practices, and HAV vaccination programs are crucial to reducing the disease burden.

Validation of a Simplified Laboratory-Based HCV Clearance Definition Using New York City Hepatitis C Program and Surveillance Data.

Laboratory-based hepatitis C virus (HCV) clearance cascades are an important tool for health departments to track progress toward HCV elimination, but a laboratory-based definition of HCV clearance has not yet been validated. To compare agreement between a laboratory-based HCV clearance definition with a clinical cure definition. Observational. New York City Department of Health and Mental Hygiene HCV surveillance system data and New York City hepatitis C linkage-to-care program data. Linkage-to-care program participants who were diagnosed with hepatitis C and enrolled in the linkage-to-care program from July 1, 2016, through June 30, 2020. Percent agreement between a laboratory-based HCV clearance definition (surveillance system) and a clinical cure definition (program data). Among 591 program participants with known treatment outcome, the laboratory-based HCV clearance definition and clinical cure definition were concordant in 573 cases (97%). A laboratory-based HCV clearance definition based on public health surveillance data can be a reliable source for monitoring HCV elimination.

Impact of Chronic Hepatitis C Virus on Acute Kidney Injury After Living Donor Liver Transplantation.

Acute kidney injury (AKI) is one of the most common complications after liver transplantation (LT) and can significantly impact outcomes. The presence of hepatitis C virus (HCV) infection increases the risk of AKI development. However, the impact of HCV on AKI after LT has not been evaluated. The aim of this study was to assess the effect of HCV on AKI development in patients who underwent LT. Between January 2008 and April 2023, 2183 patients who underwent living donor LT (LDLT) were included. Patients were divided into 2 groups based on the presence of chronic HCV infection. We compared LT recipients using the propensity score matching (PSM) method. Factors associated with AKI development were evaluated using multiple logistic regression analysis. In addition, 1-year mortality and graft failure were assessed using a Cox proportional regression model. Among 2183 patients, the incidence of AKI was 59.2%. After PSM, the patients with HCV showed a more frequent development of AKI (71.9% vs 63.9%, P = .026). In multivariate analysis after PSM, HCV was associated with AKI development (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.06-2.20, P = .022), 1-year mortality (Hazard ratio [HR], 1.98; 95% CI, 1.12-3.52, P = .019), and graft failure (HR, 2.12; 95% CI, 1.22-3.69, P = .008). The presence of HCV was associated with increased risk for the development of AKI, 1-year mortality, and graft failure after LT.

Integrating Universal Hepatitis C Screening into Adolescent Well Visits is a "Win-Win" Scenario: Rationale and Demonstration of Real-World Feasibility and Implementation.

Hepatitis C virus (HCV) testing is recommended for all adults 18 years and older to increase identification of those with infection and facilitate prompt referral for curative antiviral therapy. While critical to promote elimination, this strategy excludes a key demographic group who are clearly at risk of undetected HCV infection and who could benefit from early treatment: adolescents. In this paper, we review the available data on the burden of HCV and the close association with injection drug use, discuss the rationale of universal testing in adolescents and, finally, present data from a quality improvement project implementing HCV testing into routine adolescent health visits.

Comparison of Characteristics and Outcomes of Hepatitis B and Hepatitis C Patients in the Fars Hepatitis Registry

Background: Hepatitis, which refers to liver inflammation, can have various causes, with viral hepatitis being the most common. Objectives: This study aimed to compare demographic and laboratory variables, risk factors, and outcomes between Hepatitis B (HBV) and Hepatitis C (HCV) patients in the Fars hepatitis registry. Methods: In this cross-sectional study, a total of 6,690 eligible patients, consisting of 3,840 (57.4%) with HBV and 2,820 (42.6%) with HCV, were assessed from the database covering the period from 1995 to 2023. Comparisons between HBV and HCV were made using the Chi-square test, Fisher's exact test, or independent sample t-test with SPSS software. Results: The average age of the patients was 52.56 years (standard deviation: 13.24). Significant differences were found between HBV and HCV patients regarding sex, marital status, education level, family history of HBV and HCV, smoking status, drug use, and body mass index (P < 0.001 for all). Hepatitis B patients had a higher prevalence of dental procedures (P < 0.001) and uncertain sexual contacts (P = 0.009), while blood transfusion, intravenous drug use, major thalassemia (P < 0.001 for all), tattoos (P = 0.004), and hemodialysis (P = 0.001) were more common in HCV patients. Hepatitis C patients showed higher levels of liver enzymes (P < 0.001) and total bilirubin (P = 0.002) but lower levels of albumin (P < 0.001) and prothrombin time (P = 0.034) compared to HBV patients. Cirrhosis was also more common in HCV patients (P < 0.001). Conclusions: Our findings highlight different patterns of demographic factors, risk factors, and outcomes between HBV and HCV patients, which could influence their prevention and management strategies.

Association between Chronic Hepatitis B/C and Incidence of Osteoporosis and Bone Fractures: Results from a Retrospective Cohort Study.

Background: Osteoporosis and bone fractures affect health and quality of life. Since bone disease is multifactorial, identifying risk factors is key in prevention. There are multiple reports on how viral hepatitis, especially chronic hepatitis B (CHB) and chronic hepatitis C (CHC), are affecting bone disease, but results vary. Here, we analyzed the potential association between CHB/CHC and osteoporosis or bone fractures in a large outpatient cohort in Germany. Methods: We included 3136 outpatients with CHB and 15,608 matched non-hepatitis individuals as well as 2867 outpatients with CHC and 14,335 matched non-hepatitis individuals from the Disease Analyzer Database between 2005 and 2022. The main outcome was the 5-year cumulative incidence of osteoporosis and bone fractures as a function of either CHB or CHC. Results: Within 5 years of the index date, 2.9% vs. 1.6% of patients with and without CHB were diagnosed with osteoporosis (p = 0.001) and 1.0% vs. 0.4% were diagnosed with bone fractures (p < 0.001). Moreover, 3.3% of CHC patients and 2.2% of individuals without hepatitis C were diagnosed with osteoporosis (p = 0.002). In Cox regression analyses, CHB was significantly associated with an increased risk for osteoporosis (HR: 1.76) and fractures (HR:2.43) and CHC with osteoporosis (HR: 1.54). For both CHB and CHC, the association with osteoporosis was restricted to the female subgroup. Conclusions: CHB and CHC are associated with osteoporosis in women. CHB in male patients is associated with a higher risk of fractures. More research is needed to understand the underlying pathophysiological mechanisms.

Transforming growth factor-beta and Epithelial-mesenchymal transition is considered an attractive pivotal Genetic-Biomarker for Hepatocellular carcinoma with hepatitis C virus-infection patients

Abstract Introduction/Objective Hepatocellular carcinoma (HCC) is the most common cause of cancer worldwide. HCC is induced by hepatitis C-virus (HCV) which represents a major health problem in Egypt. The transforming growth factor- beta (TGF-β) is a potent cytokine that has a multifunctional pro-fibrotic activity, for enhancing liver-inflammation, fibrosis, tumor-progression, and metastasis. TGF-β has a vital role in the regulation of tumorigenesis, by controlling epithelial-mesenchymal-transition (EMT), apoptosis, proliferation, and differentiation process. The dysregulation of TGF-β, Wnt/β-catenin signaling pathways, by HCV-core protein is implicated in the development of HCC. Methods/Case Report The study aims to determine the effect of the HCV-infection in HCC patients with a set of growth-factors, EMT, and anti-apoptotic protein expression levels by using western blotting and immunohistochemistry staining analysis. Results (if a Case Study enter NA) These results observed an insignificant increase in the expression of TGF-β protein for HCC/HCV-infected cells compared to the HCV-uninfected cells, and the expression of the β-catenin protein level is elevated in the nucleus. Also, it showed that Bcl-2 protein is a significant increase in HCV-infected when compared to HCV-free groups. Positive staining for p53 protein was detected in the HCC/HCV-infected, more than in HCC/HCV-uninfected cells. This data indicated that the core-protein of HCV can switch TGF-β from a tumor suppressor to a tumor promoter by suppressing apoptosis of hepatocytes and increasing EMT expression by activation of Wnt/β-catenin signaling pathway. Therefore, HCV-core protein enhances the nuclear accumulation of β-catenin expression protein to activate downstream target genes, which regulate cell-growth and cell-cycle progression. Conclusion It is speculated that HCV may exert an anti-apoptotic effect, and thus enhance tumorigenesis. Also, the accumulation of nuclear Wnt/β-catenin and p53 correlates with TGF-β expression, typically a late event in hepato- carcinogenesis. Taken together, the expression level of TGF-β, Wnt/β-catenin, Bcl-2, and p53 genotype in HCV is considered an indicator of shortened survival in patients, and may be an attractive clinically pivotal genetic biomarker to mediate liver pathogenesis.

Predictors of early and interim culture un-conversion in multidrug-resistant/rifampicin-resistant tuberculosis: a retrospective multi-center cohort study in China

BackgroundWe aimed to evaluate the predictors for early and interim culture conversion within 2 months and 6 months of treatment in multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) patients in China.MethodsThis study included adult MDR/RR-TB patients with a positive baseline sputum culture from 8 institutions located in different cities in China from May 2018 to January 2022. We mainly used logistic regression model to derive possible predictors of early and interim culture conversion.ResultsA total of 813 patients were enrolled and 28.5% of them received multidrug-resistant treatment regimens containing bedaquiline. Of these, 362 (44.5%) patients experienced culture conversion within 2 months of treatment, and 649 (79.8%) within 6 months. The results of the multivariable logistic regression analysis revealed that acid-fast bacilli smear positive (adjusted odds ratio [aOR] = 1.637, 95% confidence interval [CI] = 1.197–2.238), cavities (aOR = 1.539, 95% CI = 1.132–2.092), bilateral disease (aOR = 1.638, 95% CI = 1.183–2.269), and viral hepatitis (aOR = 2.585, 95% CI = 1.189–5.622) were identified as risk factors for early culture un-conversion within 2 months of treatment. Additionally, smoking history (aOR = 2.197, 95% CI = 1.475–3.273), previous treatment for tuberculosis (aOR = 1.909, 95% CI = 1.282–2.844), bilateral disease (aOR = 2.201, 95% CI = 1.369–3.537), viral hepatitis (aOR = 2.329, 95% CI = 1.094–4.962) were identified as risk factors for interim culture un-conversion within 6 months of treatment, while patients with regimen containing bedaquiline (aOR = 0.310, 95% CI = 0.191–0.502) was a protective factor.ConclusionsA history of smoking, a baseline sputum AFB smear positive, lung cavities, bilateral disease, previous anti-tuberculosis treatment, or a comorbidity of viral hepatitis can be used as the predictors for early and interim culture un-conversion in MDR/RR-TB patients, while bedaquiline was a protective factor .

Thrombospondin 2 as a Predictive Biomarker for HCC inHepatitis C Patients: A Longitudinal Study Following DAA Therapy.

This multicentre study investigated the dynamics of thrombospondin 2 (TSP2) levels during direct-acting antiviral (DAA) therapy in hepatitis C virus (HCV) infected patients and evaluated TSP2's potential as a predictive marker for hepatocellular carcinoma (HCC). All 134 participants achieved sustained virological response at 12 weeks (SVR12) with DAA therapy, and serum TSP2 levels significantly decreased from before and after treatment (p < 0.001). During the median follow-up period of 6.0 years, HCC after DAA therapy was observed in 16 patients (11.9%). Patients with serum TSP2 High (≥ 32 ng/mL) at SVR12 had a significantly higher cumulative occurrence of HCC than did those without (26.5% vs. 7.0%, p = 0.0033). A multivariate Cox proportional hazards model identified male gender (HR 4.84, p = 0.005), HCC history (HR 4.61, p = 0.017) and TSP2 High (HR 3.93, p = 0.009) as significant independent predictors of HCC occurrence after DAA therapy. The model had a high concordance index of 0.878. Additionally, combining TSP2 High and FIB-4 High (≥ 3.538) at SVR12 yielded high specificity and negative predictive value (0.941 and 0.917, respectively) for predicting HCC. Kaplan-Meier analysis showed a higher HCC incidence in the TSP2 High + FIB-4 High group (log-rank p < 0.0001). In conclusion, TSP2 may be a promising biomarker for personalised HCC surveillance in DAA-treated hepatitis C patients.

Acute toxicity and anti-inflammatory activity of an improved traditional medicine developed in Burkina Faso

An Improved Traditional Medicine (ITM) in capsule form presented by traditional health practitioners in Burkina Faso as used for hepatoprotective and hepatocurative treatment for viral hepatitis B. The study's main objective was to investigate the anti-inflammatory properties of this ITM, which is used in treating viral hepatitis B in traditional medicine in Burkina Faso. Phytochemical screening revealed the presence of flavonoids, saponins, tannins, coumarins, alkaloids, sterols and triterpenes. The in vitro anti-inflammatory assay inhibited LOX by 15.69 ± 0.50% at a 100 µg/mL concentration. The LD50 was estimated to be greater than 5000 mg/kg. In vivo activity using the carrageenan anti-oedema test showed good dose-dependent anti-inflammatory activity of ITM at 30, 65 and 130 mg/kg bw. After 3 hours, the extract at various doses reduced edema to over 50% inhibition. After 5 h, oedema was reduced to 85.209% at the 130 mg/kg. However, the reference acetylsalicylic acid (ASA) at 100 mg/kg bw showed a percentage of 85.048% at 5 h. The IC50 obtained after the ABTS, FRAP and LPO antioxidant tests of the phytomedicine were 351.00 µg/mL, 353.20 mM EAA/L and 81.13%. However, the IC50 with the DPPH method was higher than 104 mg/mL. The phytomedicine would have anti-inflammatory and antioxidant properties due to the presence of bioactive phytochemicals on inflammation and free radicals. Keywords: ITM, Phytochemical, Acute toxicity, Anti-inflammatory, Antioxidants

STUDY OF THE ENDOMETRIAL GLANDULAR COMPONENT IN WOMEN WITH FERTILITY AND POST-COVID SYNDROME IN ANAMNESIS

The aim. To increase the effectiveness of the endometrial endometrial glandular component study in women with infertility and post-COVID syndrome. Materials and methods. A study was conducted at the State institution "Carpathian Human Reproduction Centre" of the Ministry of Health of Ukraine in the period from 2022 to the end of the first half-year of 2024. There were included 80 women in the experimental group and 40 women in the control group. The selection criterion for the study group was the presence of documented post-COVID syndrome (COVID-19 symptoms lasted longer than 12 weeks). The selection criterion for the control group was the absence of confirmed SARS-CoV-2 virus in the anamnesis. The following characteristics were common for both groups: diagnosed infertility, age – 25-42 years, written informed consent of the patient to participate in the study. The criteria for exclusion from the study for patients of both groups were: detection of human immunodeficiency virus, viral hepatitis, other sexually transmitted infections, tuberculosis of the genitourinary system, malignant diseases, mental disorders that make communication with person impossible or the awareness of written consent is questioned. General clinical and laboratory examinations and transvaginal sonographic examination of the pelvic organs were performed in the middle stage of proliferation and the middle stage of secretion according to the calendar calculation the menstrual cycle. A visually guided diagnostic office hysteroscopy was performed with the collection of biological material from the most changed areas (biopsies were collected in the middle stage of proliferation and the middle stage of secretion in different menstrual cycles). A routine staining of samples with hematoxylin-eosin, morphometry of the endometrial glandular component, optical determination of the number of glands and measurement of the diameter of the lumen of the studied glands, considering the possible measurement error, glandular-stromal ratio, functional activity of the glands, were performed. A histochemical PAS-reaction to identify the glycoproteins of gland secretions and immunohistochemical staining of the glandular epithelium to express the receptivity of the glands to estrogen and progesterone were carried out. The results. After conducting the PAS-reaction, a higher secretion was noted in the glands than in the stroma of the endometrium during the period of the implantation window in both cohorts. No statistically significant difference between the groups in the amount of glycogen of the middle proliferative phase in the glands (p=0.315) or stroma (p=0.486). Glycogen in this phase was visualized of very small granules and coarse granules, without their formation in clusters. A decrease in secretion was established in 16 (40%) patients of the control group and 49 (61.3%) women of the experimental group in the middle secretory phase, which was statistically significant (p=0.028). A decrease in the expression level of the progesterone receptor in the middle secretory phase was found to be significantly more pronounced in the experimental group than in the control group (р=0.044). Conclusions. In the middle secretory phase, a decrease in the secretion of glycogen by the endometrial glands and a decrease in the level of expression of the progesterone receptor in endometrial biopsies were detected by the routine histological, histochemical techniques and immunohistochemical stude in women with infertility and a history of post-COVID syndrome.

Metastatic Melanoma of Unknown Primary with Plasmacytoid Morphology Presenting as Acute Liver Failure

Abstract Introduction/Objective Viral hepatitis, drug toxicity, and autoimmune disorders are common etiologies of acute liver failure (ALF). Very rarely, a cause like metastatic melanoma may present as a primary driver of ALF. Malignant melanoma is histologically diverse and plasmacytoid melanoma is an unusual variant that may present as a solitary tumor or metastatic disease. Methods/Case Report A 48-year-old female presented with 2 weeks of right upper quadrant pain, nausea, coffee ground emesis and bleeding per rectum. She had no history of liver disease or alcohol use. On presentation, AST was 83 U/L, ALT was 29U/L, ALP was 159U/L and total bilirubin was 12.7g/dl. Viral hepatitis panel, HIV and chronic liver disease workup was negative. Esophagogastroduodenoscopy and colonoscopy showed no sources of bleeding. She was diagnosed with decompensated cirrhosis, ALF, and acute kidney injury from hepatorenal syndrome. Cirrhosis and multifocal indeterminate T1 hyper/T2 hypo intense lesions (dysplastic or regenerative nodules) were seen on MRI. Liver biopsy revealed metastatic melanoma. Almost entire liver parenchyma on biopsy was replaced by a population of neoplastic cells with plasmacytoid features. Immunostaining was positive for MART-1, HMB45 and SOX-10. Staining for Pan Cytokeratin and CK-7 highlighted the bile ducts and negative staining was seen for CK20, CD3, CD20, PAX-8, GATA-3, CDX-2 and P63. No primary lesion was found. It was deemed unlikely that she would benefit from therapy before complications occur. She passed away in 16 days. Results (if a Case Study enter NA) NA Conclusion In most cases of ALF associated with malignant melanoma, the liver may have a seemingly normal appearance on imaging studies due to the distinctive histology of leukemoid tumor infiltration within the liver sinusoids, resulting in sinusoidal obstruction and subsequent hepatocellular dysfunction. The rapidity of liver failure in these cases is related to the replacement of liver parenchyma by malignant cells. The plasmacytoid morphology is seen in a variety of malignancies and to avoid a potential misdiagnosis of an aggressive malignant melanoma, it is imperative to perform a thorough histopathological evaluation aided with immunohistochemistry. It is important to keep in mind that the potential involvement of malignant tumor cell infiltration may cause ALF and early histological assessment with a liver biopsy may be of paramount significance and may possibly change the course of the disease.

CHARACTERISTICS OF THE HOSPITALIZATION PERIOD IN PATIENTS WHO DIED AS A RESULT OF COVID-19 WITH ACUTE CARDIOVASCULAR COMPLICATIONS

The aim. To identify adverse risk factors in hospitalized patients with fatal consequences of the coronavirus disease-2019 and its acute cardiovascular complications. Materials and methods. A retrospective study was conducted of 66 people in the study group with acute respiratory failure and cardiovascular complications due to COVID-19. The comparison group was 48 people who died of acute cardiovascular events without SARS-CoV-2 infection or other bacterial or viral diseases. The criteria for inclusion in the study group were the presence of confirmed SARS-CoV-2 infection by the polymerase chain reaction method, the presence of acute cardiovascular complications during COVID-19, and patients hospitalized during its treatment. Inclusion criteria for the comparison group were hospitalized patients with acute cardiovascular diseases that led to death without SARS-CoV-2 infection. The exclusion criteria for both groups were: age before 18 years old; absence of informed consent of the authorized person of dead person or the decision of the authorized person to withdraw from the study at any of the stages; the presence of other co-infections that could have a cumulative negative effect on the state of the respiratory and cardiovascular systems (flu virus, hepatitis virus, human immunodeficiency virus, pathogens that led to symptoms of acute intestinal infections). Age and gender distribution, comorbidities, length of hospitalization, and laboratory markers were evaluated in both cohorts. Cardiovascular complications were confirmed by the results of ultrasound examinations, computed tomography angiography and comparison with postmortem morphological findings in autopsy reports for the analysis of the current study,. The results. There were 48 men (72.7%) and 18 women (27.3%) in the study group of 66 patients who developed cardiovascular complications at the background of COVID-19, and in the comparison group – 39 men (81.3%) and 9 women (18.7%), which indicates acceptable comparability of the groups among themselves due to sex (p=0.374) and age (p=0.338). In particular, the age median for men in the study group was 65 years (IQR - 21 years), with minimum and maximum age values ​​– 36 and 83 years, respectively; the median age for women in the study group was also 65 years (IQR – 12.5 years), with the lower and upper age limits in the group being 41 and 78 years. The age median for men in the comparison group was 62 years (IQR 15 years), with a lower and upper age range of 54 and 81 years. The age median for women in the comparison group was 68 years (IQR – 16.5 years), with the lower and upper age values ​​in the group being 55 and 79 years. Men and women of the comparison group did not statistically differ from each other in terms of age (р=0.412). A significant difference was found between the length of hospitalization in both cohorts (р˂0.00001) – the median length of stay in hospital for the study group was 15 days, and for the comparison group – 10 days. It was established that malignant diseases were an additional concomitant factor of mortality in the group of patients with COVID-19 (р=0.043). The percentage ratio of neutrophils (p=0.048) and lymphocytes (p=0.031) in patients of the study group significantly differed. Conclusions. Unfavorable risk factors in patients with fatal consequences of Coronavirus disease-2019 and acute cardiovascular complications were concomitant oncological pathology, a long period of hospitalization, and changes in the percentage ratio of neutrophils and lymphocytes.

Evaluation of Hepatitis C Virus Transmission Through Endoscopy Procedures in the Country of Georgia.

Exposure to healthcare procedures might be a source of hepatitis C virus (HCV) transmission in Georgia, one of the few countries currently on track to eliminate hepatitis C. While there has been a history of iatrogenic transmission of HCV, the risk of HCV transmission related to endoscopic procedures has not been previously assessed in Georgia. The goal of this study was to assess HCV seroconversion among individuals undergoing endoscopic procedures to estimate the relative role and incidence of HCV infection attributable to endoscopic procedures. A prospective cohort study was conducted in four endoscopy units in two cities (Tbilisi and Kutaisi) of Georgia during April-September, 2021. Recruitment of study participants was conducted using convenience sampling, and every eligible patient was approached and invited to participate in the study. Study population included adults (age ≥ 18 years) who received an endoscopic procedure (gastroscopy, colonoscopy and bronchoscopy) in inpatient or outpatient unit at the study sites. HCV antibody (anti-HCV) testing was conducted using rapid diagnostic test (RDT) on the same day they underwent the endoscopic procedure. Patients with a non-reactive anti-HCV baseline test were retested after 6 months. Patients with reactive baseline tests were excluded from the study and linked to further testing and care. Participants with a reactive result on follow-up RDTs were retested using a lab-based anti-HCV and HCV ribonucleic acid (RNA) test. A total of 981 HCV antibody non-reactive participants were enrolled; 590 (64.8%) of them were reached and retested after 6 months. At retesting, two out of 590 (0.3%) individuals had a reactive anti-HCV result on RDT and both were negative on laboratory-based anti-HCV and HCV RNA tests. Based on the results of this study, endoscopic procedures were not shown to contribute to HCV transmission in Georgia.

HEV ORF2 protein-antibody complex deposits are associated with glomerulonephritis in hepatitis E with reduced immune status

Hepatitis E virus (HEV) infection, one of the most common forms of hepatitis worldwide, is often associated with extrahepatic, particularly renal, manifestations. However, the underlying mechanisms are incompletely understood. Here, we report the development of a de novo immune complex-mediated glomerulonephritis (GN) in a kidney transplant recipient with chronic hepatitis E. Applying immunostaining, electron microscopy, and mass spectrometry after laser-capture microdissection, we show that GN develops in parallel with increasing glomerular deposition of a non-infectious, genome-free and non-glycosylated HEV open reading frame 2 (ORF2) capsid protein. No productive HEV infection of kidney cells is detected. Patients with acute hepatitis E display similar but less pronounced deposits. Our results establish a link between the production of HEV ORF2 protein and the development of hepatitis E-associated GN in the immunocompromised state. The formation of glomerular IgG-HEV ORF2 immune complexes discovered here provides a potential mechanistic explanation of how the hepatotropic HEV can cause variable renal manifestations. These findings directly provide a tool for etiology-based diagnosis of hepatitis E-associated GN as a distinct entity and suggest therapeutic implications.

NHC-Catalyzed Aldimine Umpolung/6π-Electrocyclization Cascade to Access Tetracyclic Dihydrochromeno Indoles.

The umpolung of aldimines using N-heterocyclic carbenes (NHCs) is less explored compared to the established polarity reversal of aldehydes. Described herein is an NHC-catalyzed imine umpolung /6π-electrocyclization cascade, which leads to the atom- and pot-economic synthesis of biologically important dihydrochromeno indoles. For the first time, the nucleophilic aza-Breslow intermediates have been intercepted with unactivated alkynes. Preliminary mechanistic and DFT studies shed light on the role of the phenolic -OH moiety in promoting the addition of the aza-Breslow intermediate to the unactivated alkyne via an intramolecular proton transfer in a stepwise manner. DFT studies also support the regioselectivity preference for the 5-exo-dig cyclization pathway, leading to the exclusive formation of the indole products. Moreover, a comparison of Gibbs free energies provides insight into a thermodynamically preferred 6π-electrocyclization over a competing oxa-Michael pathway. Further, this strategy is applied to the formal synthesis of a Hepatitis C Virus (HCV) NS5A inhibitor in a step-economical method.

NHC‐Catalyzed Aldimine Umpolung/6π‐Electrocyclization Cascade to Access Tetracyclic Dihydrochromeno Indoles

The umpolung of aldimines using N‐heterocyclic carbenes (NHCs) is less explored compared to the established polarity reversal of aldehydes. Described herein is an NHC‐catalyzed imine umpolung /6π‐electrocyclization cascade, which leads to the atom‐ and pot‐economic synthesis of biologically important dihydrochromeno indoles. For the first time, the nucleophilic aza‐Breslow intermediates have been intercepted with unactivated alkynes. Preliminary mechanistic and DFT studies shed light on the role of the phenolic ‐OH moiety in promoting the addition of the aza‐Breslow intermediate to the unactivated alkyne via an intramolecular proton transfer in a stepwise manner. DFT studies also support the regioselectivity preference for the 5‐exo‐dig cyclization pathway, leading to the exclusive formation of the indole products. Moreover, a comparison of Gibbs free energies provides insight into a thermodynamically preferred 6π‐electrocyclization over a competing oxa‐Michael pathway. Further, this strategy is applied to the formal synthesis of a Hepatitis C Virus (HCV) NS5A inhibitor in a step‐economical method.

Acacetin, a Natural Flavone with Potential in Improving Liver Disease Based on Its Anti-Inflammation, Anti-Cancer, Anti-Infection and Other Effects.

Liver disease is a global public problem, and the cost of its therapy is a large financial burden to governments. It is well known that drug therapy plays a critical role in the treatment of liver disease. However, present drugs are far from meeting clinical needs. Lots of efforts have been made to find novel agents to treat liver disease in the past several decades. Acacetin is a dihydroxy and monomethoxy flavone, named 5,7-dihydroxy-4'-methoxyflavone, which can be found in diverse plants. It has been reported that acacetin exhibits multiple pharmacological activities, including anti-cancer, anti-inflammation, anti-virus, anti-obesity, and anti-oxidation. These studies indicate the therapeutic potential of acacetin in liver disease. This review discussed the comprehensive information on the pathogenesis of liver disease (cirrhosis, viral hepatitis, drug-induced liver injury, and hepatocellular carcinoma), then introduced the biological source, structural features, and pharmacological properties of acacetin, and the possible application in preventing liver disease along with the pharmacokinetic and toxicity of acacetin, and future research directions. We systemically summarized the latest research progress on the potential therapeutic effect of acacetin on liver disease and existing problems. Based on the present published information, the natural flavone acacetin is an anticipated candidate agent for the treatment of liver disease.