A comparative study of different antiviral treatment protocols in HCV related cryoglobulinemic vasculitis.

The treatment of HCV and its sequelae are used to be predominantly based on Interferon (IFN). However, this was associated with significant adverse events as a result of its immunostimulant capabilities. Since their introduction, the directly acting antiviral drugs (DAAs), have become the standard of care to treat of HCV and its complications including mixed cryoglobulinemic vasculitis (MCV). In spite of achieving sustained viral response (SVR), there appeared many reports describing unwelcome complications such as hepatocellular and hematological malignancies as well as relapses. Prolonged inflammation induced by a multitude of factors, can lead to DNA damage and affects BAFF and APRIL, which serve as markers of B-cell proliferation. We compared, head-to-head, three antiviral protocols for HCV-MCV treatment As regards the treatment response and relapse, levels of BAFF and APRIL among pegylated interferon α-based and free regimens (Sofosbuvir + Ribavirin; SOF-RIBA, Sofosbuvir + Daclatasvir; SOF-DACLA). Regarding clinical response HCV-MCV and SVR; no significant differences could be identified among the 3 different treatment protocols, and this was also independent form using IFN. We found no significant differences between IFN-based and free regimens DNA damage, markers of DNA repair, or levels of BAFF and APRIL. However, individualized drug-to-drug comparisons showed many differences. Those who were treated with IFN-based protocol showed decreased levels of DNA damage, while the other two IFN-free groups showed increased DNA damage, being the worst in SOF-DACLA group. There were increased levels of BAFF through follow-up periods in the 3 protocols being the best in SOF-DACLA group (decreased at 24 weeks). In SOF-RIBA, CGs relapsed significantly during the follow-up period. None of our patients who were treated with IFN-based protocol had significant clinico-laboratory relapse. Those who received IFN-free DAAs showed a statistically significant relapse of constitutional manifestations. Our findings suggest that IFN-based protocols are effective in treating HCV-MCV similar to IFN-free protocols. They showed lower levels of DNA damage and repair. We believe that our findings may offer an explanation for the process of lymphoproliferation, occurrence of malignancies, and relapses by shedding light on such possible mechanisms.

Feasibility, safety, efficacy and potential scaling-up of sofosbuvir-based HCV treatment in Central and West Africa: (TAC ANRS 12311 trial).

Access to Hepatis C treatment in Sub-Saharan Africa is a clinical, public health and ethical concern. The multi-country open-label trial TAC ANRS 12311 allowed assessing the feasibility, safety, efficacy of a specific care model of HCV treatment and retreatment in patients with hepatitis C in Sub Saharan Africa. Between November 2015 and March 2017, with follow-up until mid 2019, treatment-naïve patients with HCV without decompensated cirrhosis or liver cancer were recruited to receive 12 week-treatment with either sofosbuvir + ribavirin (HCV genotype 2) or sofosbuvir + ledipasvir (genotype 1 or 4) and retreatment with sofosbuvir + velpatasvir + voxilaprevir in case of virological failure. The primary outcome was sustained virological response at 12 weeks after end of treatment (SVR12). Secondary outcomes included treatment adherence, safety and SVR12 in patients who were retreated due to non-response to first-line treatment. The model of care relied on both viral load assessment and educational sessions to increase patient awareness, adherence and health literacy. The study recruited 120 participants, 36 HIV-co-infected, and 14 cirrhotic. Only one patient discontinued treatment because of return to home country. Neither death nor severe adverse event occurred. SVR12 was reached in 107 patients (89%): (90%) in genotype 1 or 2, and 88% in GT-4. All retreated patients (n = 13) reached SVR12. HCV treatment is highly acceptable, safe and effective under this model of care. Implementation research is now needed to scale up point-of-care HCV testing and SVR assessment, along with community involvement in patient education, to achieve HCV elimination in Sub-Saharan Africa.

Respiratory syncytial virus: A new era / Virus respiratorio sincitial: un nuevo tiempo

Respiratory syncytial virus (RSV) is a major public health problem that has undergone significant changes in recent years. First of all, it has become easier to diagnose with highly reliable and rapidly available confirmatory tests. This has led to a better understanding of its epidemiology and RSV has gone from being a disease of the pediatric age group, severe only in infants and immunosuppressed children, to being a common disease in people of all ages, particularly important in patients of advanced age or with immunosuppressive diseases. Recent therapeutic and prophylactic advances, both with long-lasting monoclonal antibodies and vaccines, are another reason for satisfaction. For these reasons, the COVID and Emerging Pathogens Committee of the Illustrious Official College of Physicians of Madrid (ICOMEM) has considered it pertinent to review this subject in the light of new knowledge and new resources for dealing with this infection. We have formulated a series of questions that we believe will be of interest not only to members of the College but also to any non-expert in this subject, with a particular focus on the situation of RSV infection in Spain. (AU)

El Virus Respiratorio Sincitial (VRS), es un problema de salud pública de primera magnitud que en años recientes ha experimentado cambios muy importantes. En primer lugar, se ha producido una mayor facilidad diagnóstica con pruebas confirmatorias altamente fiables y rápidamente disponibles. Esto ha permitido conocer mejor su epidemiología y VRS ha pasado de ser una enfermedad de la edad pediátrica, grave sólo en lactantes y niños inmunodeprimidos, a ser una enfermedad común en personas de toda edad, particularmente importante en pacientes de edades avanzadas o con enfermedades que inmunodeprimen. Los avances terapéuticos y profilácticos, recientes, tanto con anticuerpos monoclonales de larga duración como con vacunas, constituyen otro motivo de satisfacción. Por estos motivos, el Comité de COVID y de patógenos emergentes del Ilustre Colegio Oficial de Médicos de Madrid (ICOMEM) ha considerado pertinente revisar este tema, a la luz de los nuevos conocimientos y de los nuevos recursos para afrontar esta infección. Hemos formulado una serie de preguntas que creemos de interés no sólo para los colegiados si no para cualquier persona no experta en este tema, con una vista particular en la situación de la infección por VRS en España. (AU)

Favipiravir Treatment Prolongs Survival in a Lethal BALB/c Mouse Model of Ebinur Lake Virus Infection.

Orthobunyavirus is the largest and most diverse genus in the family Peribunyaviridae. Orthobunyaviruses are widely distributed globally and pose threats to human and animal health. Ebinur Lake virus (EBIV) is a newly classified Orthobunyavirus detected in China, Russia, and Kenya. This study explored the antiviral effects of two broad-spectrum antiviral drugs, favipiravir and ribavirin, in a BALB/c mouse model. Favipiravir significantly improved the clinical symptoms of infected mice, reduced viral titer and RNA copies in serum, and extended overall survival. The median survival times of mice in the vehicle- and favipiravir-treated groups were 5 and 7 days, respectively. Favipiravir significantly reduced virus titers 10- to 100-fold in sera at all three time points compared to vehicle-treated mice. And favipiravir treatment effectively reduced the virus copies by approximately 10-fold across the three time points, relative to vehicle-treated mice. The findings expand the antiviral spectrum of favipiravir for orthobunyaviruses in vivo.

A nanobody-mediated drug system against largemouth bass virus delivered by bacterial nanocellulose in Micropterus salmoides.

Diseases caused by pathogens severely hampered the development of aquaculture, especially largemouth bass virus (LMBV) has caused massive mortality and severe economic losses to the culture of largemouth bass (Micropterus salmoides). Considering the environmental hazards and human health, effective and environmentally friendly therapy strategy against LMBV is of vital importance and in pressing need. In the present study, a novel nanobody (NbE4) specific for LMBV was selected from a phage display nanobody library. Immunofluorescence and indirect ELISA showed that NbE4 could recognize LMBV virions and had strong binding capacity, but RT-qPCR evidenced that NBE4 did not render the virus uninfectious. Besides, antiviral drug ribavirin was used to construct a targeted drug system delivered by bacterial nanocellulose (BNC). RT-qPCR revealed that NbE4 could significantly enhance the antiviral activity of ribavirin in vitro and in vivo. The targeted drug delivery system (BNC-Ribavirin-NbE4, BRN) reduced the inflammatory response caused by LMBV infection and improved survival rate (BRN-L, 33.3 %; BRN-M, 46.7 %; BRN-H, 56.7 %)compared with control group (13.3 %), ribavirin group (RBV, 26.7 %) and BNC-ribavirin (BNC-R, 40.0 %), respectively. This research provided an effective antiviral strategy that improved the drug therapeutic effect and thus reduced the dosage.

Impact of ITPA gene polymorphism for predicting anemia and treatment outcome in HCV infected patients taking Sofosbuvir Ribavirin therapy.

BACKGROUND: Globally, 80 million people are suffering from chronic Hepatitis C virus (HCV) infection. Sofosbuvir ribavirin-based anti-HCV therapy is associated with anemia and other adverse effects. Polymorphisms of Inosine triphosphatase (ITPA) gene may cause functional impairment in the Inosine triphosphate pyrophosphatase enzyme, resulting in enhanced sustained viral response (SVR) and protection from ribavirin-associated anemia in patients on therapy. The study objective was to investigate the effect of Inosine triphosphatase gene polymorphism on SVR achievement, hemoglobin decline and ribavirin dose reduction in patients on therapy. METHODS: This prospective cohort study was of 170 hepatitis C infected patients received 6-month sofosbuvir ribavirin therapy. Patient viral load, reduction in ribavirin amount, liver function test, and complete blood count were noted monthly. Inosine triphosphatase variants rs1127354 and rs7270101 were assessed through the restriction fragment length polymorphism and confirmed using Sanger sequencing. The impact of polymorphism on cumulative reduction of ribavirin, and anti-HCV therapy outcome were studied. RESULTS: A total of 74.3% of patients had ITPA rs1127354 CC genotype, 25.7% were CA and AA 0%. The frequency of ITPA genotype rs7270101-AA was 95%, AC 5%, and CC was 0%. ITPA rs1127354-CA had a notably positive impact on SVR achievement with a zero-relapse rate. ITPA rs1127354-CA genotype was significantly (P ˂0.05) protective against ≥ 2 g/dl Hb reduction from baseline to 1st, 2nd and 6th months of therapy. During treatment, Hb reduction ≥ 10 g/dl was frequently observed in rs1127354-CC genotype and rs7270101-AA genotype patients. Ribavirin dose reduction was significantly (P ˂0.05) high in rs1127354-CC genotype as compared to genotype CA whereas no significant difference was observed in ribavirin dose reduction in rs7270101 AA and non-AA genotype. Patient baseline characteristics such as age, body mass index, rs1127354-CC genotype, and baseline Hb were significantly associated with significant Hb reduction. CONCLUSION: Pretreatment evaluation of ITPA polymorphism can be a diagnostic tool to find out patients at risk of anemia and improve treatment adherence. ITPA genotype rs1127354-CA contributes to improved compliance with ribavirin dose and protects against hemoglobin decline in HCV patients while taking ribavirin-based therapy. However, ITPA rs1127354, rs7270101 polymorphism have no significant impact on SVR achievement.

Identification of Novel Bisamide-Decorated Benzotriazole Derivatives as Anti-Phytopathogenic Virus Agents: Bioactivity Evaluation and Computational Simulation.

As a notorious phytopathogenic virus, the tobacco mosaic virus (TMV) severely reduced the quality of crops worldwide and caused critical constraints on agricultural production. The development of novel virucides is a persuasive strategy to address this predicament. Herein, a series of novel bisamide-decorated benzotriazole derivatives were elaborately prepared and screened. Biological tests implied that the optimized compound 7d possessed the most brilliant antiviral inactive profile (EC50 = 157.6 µg/mL) and apparently surpassed that of commercial ribavirin (EC50 = 442.1 µg/mL) 2.8-fold. The preliminary antiviral mechanism was elaborately investigated via transmission electron microscopy, microscale thermophoresis (MST) determination, RT-qPCR, and Western blot analysis. The results showed that compound 7d blocked the assembly of TMV by binding with coat protein (Kd = 0.7 µM) and suppressed TMV coat protein gene expression and biosynthesis process. Computational simulations indicated that 7d displayed strong H-bonds and pi interactions with TMV coat protein, affording a lower binding energy (ΔGbind = -17.8 kcal/mol) compared with Ribavirin (ΔGbind = -10.7 kcal/mol). Overall, current results present a valuable perception of bisamide decorated benzotriazole derivatives with appreciably virustatic competence and should be profoundly developed as virucidal candidates in agrochemical.

The deleterious effects of sofosbuvir and ribavirin (antiviral drugs against hepatitis C virus) on different body systems in male albino rats regarding reproductive, hematological, biochemical, hepatic, and renal profiles and histopathological changes.

Sofosbuvir is one of the crucial drugs used in the treatment of chronic hepatitis C virus (HCV) in adults and children with compensated liver disease, including cirrhosis. It may be used alone or with other drugs. Ribavirin is an antiviral medication used to treat HCV infection. It is not effective when used alone and must be used in combination with other medications, such as sofosbuvir. This study pertains to a comprehensive assessment of the deleterious effects of sofosbuvir (an antiviral drug against chronic HCV) or sofosbuvir combined with ribavirin (an antiviral drug against RNA and DNA viruses) on several biological activities of the body, including hematological, hormonal, biochemical, histological, and immunohistochemical examinations during a long-standing period on male healthy rats. In addition, fertility assessments were performed, including sperm collections and semen parameter investigations. This study was conducted on 21 male rats divided into three equal groups. Group I (control group) received distilled water; group II (sofosbuvir group) received sofosbuvir (4 mg/kg); and group III (sofosbuvir + ribavirin) received sofosbuvir (4 mg/kg) plus ribavirin (30 ml/kg). All groups received the specific drug for six months. Blood and tissue samples were collected for hematological, hormonal, biochemical, histological, and immunohistochemical examinations. In addition, sperm collection and assessments of semen parameters were performed. Results revealed that sofosbuvir causes a highly significant decrease in the mean of most hematological, immunological, hormonal, and biochemical parameters, except for a few numbers of parameters such as neutrophils, monocytes, basophils, cortisol, GOT, and lipase, which exhibit a significant increase. The same occurred in the sofosbuvir + ribavirin group, but at much higher levels, as most hematological, immunological, hormonal, and biochemical parameters exhibit a highly significant decrease except for monocytes, triglyceride, and lipase, which exhibit a significant increase. When compared to the sofosbuvir group alone, the sofosbuvir + ribavirin group demonstrated a highly significant decline in the mean of most hematological, immunological, hormonal, and biochemical parameters except lymphocytes and triglycerides, which exhibit a substantial increase. For the reproductive parameters, both groups exhibit a significant decrease in the total sperm motility percentage. Finally, it can be concluded that sofosbuvir causes acute pancreatitis and combined immunodeficiency. Ribavirin is associated with hormonal deficiency, which indicates the occurrence of hypopituitarism. Moreover, sofosbuvir and ribavirin synergistically affect myelosuppression and cause iron-deficiency anemia. However, sofosbuvir, or its combination with ribavirin, is associated with a reduced risk of hepatocellular carcinoma. Besides, adding ribavirin to be combined with sofosbuvir improved the immunodeficiency caused by sofosbuvir; this confirms that using ribavirin with sofosbuvir reduces the side effects of both alone.

Comparative efficacy and safety of Sofosbuvir/Velpatasvir and Danoprevir for the treatment of chronic hepatitis C: the real-world data in China.

BACKGROUND: Sofosbuvir/Velpatasvir (Epclusa, ECS) is the first pan-genotype direct-acting antiviral agent (DAA) for hepatitis C virus (HCV) infection, and Danoprevir (DNV) is the first DAA developed by a Chinese local enterprise, which is suitable for combined use with other drugs to treat genotype 1b chronic hepatitis C. However, previous reports have never compared the real-world data of ECS and DNV. PATIENTS AND METHODS: 178 chronic hepatitis C patients were retrospectively recruited, and 94cases were accepted with Sofosbuvir/Velpatasvir ± Ribavirin (ECS group), and others (n = 84 treated with DNV combination therapy (DNV group). The HCV genotype, virological response, adverse effects and some laboratory biochemical indexes were contrasted between above two groups in the real world study. RESULTS: DNV group had significantly lower level of alpha-fetoprotein (AFP), lower rates of decompensated cirrhosis ( P < 0.05). ECS group possessed more 6a (31.91% vs.13.10%) while DNV group was provided with more 1b (48.81% vs. 22.34%) patients. Significantly poor liver function was detected in ECS group at 4-week treatment (ALT and AST) and 12-week follow-up (AST) (all P < 0.05). The SVR12 undetectable rates of both groups were 100%, and no serious event was observed during the treatment and follow-up in both groups. CONCLUSION: In this retrospective real-world study, the efficacy of DNV combined therapy is similar to Sofosbuvir/Velpatasvir ± Ribavirin for chronic HCV infection, and the safety is comparable. DNV based therapy is a promising regimen for chronic hepatitis C.

[Clinical comprehensive evaluation of Houyanqing Oral Liquid in treatment of acute pharyngitis].

This study systematically combed the existing evidence of Houyanqing Oral Liquid in the treatment of acute pharyngitis from the "6+1" dimensions of safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine(TCM) and carried out qualitative and quantitative analysis of the data from each dimension. The multi-criteria decision analysis(MCDA) model and CSC v2.0 were used to evaluate the clinical value of this drug, so as to provide evidence for the selection of essential drugs in the department of otolaryngology and for medical and health decision-making. The dimensions are graded A, B, C, or D. The adverse reactions of Houyanqing Oral Liquid in the treatment of acute pharyngitis were mainly manifested as abdominal pain, diarrhea, rash, etc., which were relieved after drug withdrawal. In terms of safety, it was considered that Houyanqing Oral Liquid had controllable risk and high safety, which was rated as grade B. Compared with ribavirin aerosol alone, Houyanqing Oral Liquid combined with ribavirin aerosol can significantly improve the total response rate, shorten the time to abatement of fever and di-sappearance of throat pain and mucosal congestion, and alleviate mucosal congestion and cough with sputum. With medium-quality evidence, the effectiveness was rated as grade B. Compared with ribavirin aerosol alone, Houyanqing Oral Liquid combined with ribavirin aerosol had cost-effectiveness advantages in the treatment of acute pharyngitis, and its economy was rated as grade C with the evidence of general quality. For acute pharyngitis, Houyanqing Oral Liquid can shorten the disease course and obviously relieve sore throat. Moreover, it can be used for the treatment of radioactive pharyngitis and oral ulcer, and thus its innovation was rated as grade B. With convenient and simple administration and standard and complete drug information, the suitability of this drug was rated as grade B. Houyanqing Oral Liquid is derived from the folk prescription in Hunan province and has been subjected to real-world studies, and thus the TCM characteristics was rated as grade B. According to the ratings of all the dimensions, the comprehensive value of Houyanqing Oral Liquid in the clinical treatment of acute pharyngitis was determined as grade B, with sufficient evidence and clear results. It is suggested that the results should be conditionally converted into relevant policy of clinical basic drug management according to procedures.

Vaccine Associated Measles Complicated by Suspected Measles Inclusion Body Encephalitis in a Pediatric Leukemia Patient and Stem Cell Transplant Recipient: A Focus on Clinical Evolution and Management.

BACKGROUND: Immunocompromised individuals are at increased risk for severe disease and complications from viral infections, highlighting the importance of vaccination. However, in extremely rare situations, vaccine associated viral infections can be associated with disseminated disease and complications in immunocompromised hosts. CASE: Herein, we present a case of a 1-year-old child diagnosed with acute myeloid leukemia less than 2 weeks after receiving live viral vaccines who developed acute vaccine-strain measles virus disease, later complicated by central nervous system involvement following hematopoietic stem cell transplantation. A brain biopsy specimen was positive for vaccine-strain measles virus detected by reverse transcriptase polymerase chain reaction. MANAGEMENT AND OUTCOME: She was treated with intravenous ribavirin, inosine pranobex, intrathecal interferon-alpha and donor lymphocyte infusion following measles-mumps-rubella vaccine boost. Despite these measures, the patient suffered neurologic decline and dysautonomia, expiring after compassionate extubation. Management and ideal risk mitigation strategies are discussed within the context of existing literature for this rare complication.

Chlorination of antiviral drug ribavirin: Kinetics, nontargeted identification, and concomitant toxicity evolution.

Residual antiviral drugs in wastewater may increase the risk of generating transformation products (TPs) during wastewater treatment. Therefore, chlorination behavior and toxicity evolution are essential to understand the secondary ecological risk associated with their TPs. Herein, chlorination kinetics, transformation pathways, and secondary risks of ribavirin (RBV), one of the most commonly used broad-spectrum antivirals, were investigated. The pH-dependent second-order rate constants k increased from 0.18 M-1·s-1 (pH 5.8) to 1.53 M-1·s-1 (pH 8.0) due to neutral RBV and ClO- as dominant species. 12 TPs were identified using high-resolution mass spectrometry in a nontargeted approach, of which 6 TPs were reported for the first time, and their chlorination pathways were elucidated. The luminescence inhibition rate of Vibrio fischeri exposed to chlorinated RBV solution was positively correlated with initial free active chlorine, probably due to the accumulation of toxic TPs. Quantitative structure-activity relationship prediction identified 7 TPs with elevated toxicity, concentrating on developmental toxicity and bioconcentration factors, which explained the increased toxicity of chlorinated RBV. Overall, this study highlights the urgent need to minimize the discharge of toxic chlorinated TPs into aquatic environments and contributes to environmental risk control in future pandemics and regions with high consumption of antivirals.

Effects on viral suppression and the early-immune expression of ribavirin against spring viremia of carp virus in vitro.

Spring viremia of carp virus (SVCV) is a globally distributed virus that causes severe clinical symptoms and high mortality in fish belonging to the families Cyprinidae and Siluridae. To protect the host against viral infection, understanding the relatedness between viral susceptibility and antiviral mechanisms must be crucial. Thus, we evaluated the viral suppression efficacy of ribavirin by measuring the transcription levels of viral and immune genes in vitro. The results showed that following ribavirin treatment after SVCV infection (MOI 0.1), ribavirin inhibited SVCV replication in epithelioma papulosum cyprini (EPC) cells and completely inhibited viral gene (G and N) expression at concentrations above 10 µg/mL at 48 h post-infection. Ribavirin does not directly damage SVCV particles but inhibits early viral replication. In the absence of SVCV infection, the immunological dynamics triggered by ribavirin resulted in upregulated pattern recognition receptors and proinflammatory cytokine-related genes (i.e., PI3K, MYD88, IRAK1, RIG-І, MAVS, Mx1, TNF-α, and NF-κB). Furthermore, EPC cells treated with ribavirin following SVCV infection showed upregulation of PI3K, MYD88, IRAK1, RIG-І, TNF-α, and NF-κB genes within 24 h post-SVCV infection, suggesting that ribavirin positively inhibits the SVCV infection in vitro.

Diabetic patients with chronic hepatitis C virus response compared to non diabetics when treated with directly acting antiviral therapy.

BACKGROUND AND STUDY AIMS: Hepatitis C virus (HCV) impairs glucose homoestasis, thus influences its clinical picture and prognosis. This study aimed at evaluating Diabetes mellitus (DM) on Egyptian patients with chronic hepatitis C (CHC), and its impact on their virologic response when treated with directly acting antiviral (DAA) medications. PATIENTS AND METHODS: Adult patients with CHC were divided into 2 groups; Diabetic patients, and Non diabetic patients serving as control group. All patients were subjected to thorough clinical evaluation, basic biochemical laboratory tests including fasting blood glucose/glycosylated haemoglobin (HbA1C), and virologic assay. They were treated with various combined DAAs, and were monitored during, at and after end of treatment. RESULTS: Diabetic patients constituted 9.85 % of CHC, and had generally worse laboratory tests (significantly higher transaminases, platelet count, Fib4 and hepatic steatosis) than non diabetic patients, and a less sustained virologic response (SVR) (significantly in Sofosbuvir (SOF) + pegylated interferon (PegIFN) + ribavirin (RBV), SOF + RBV, SOF + daclatasvir (DAC)). Although DM did not play a significant influence on SVR, yet Fib4 and SOF + RBV + PEG-IFN were significant factors affecting SVR among diabetics, while female gender and viraemia were significant factors affecting SVR among non diabetics. Hepatic fibrosis and SOF/RBV significantly influenced SVR in both groups. CONCLUSIONS: Diabetic patients with CHC have worse liver biochemical profile, yet DM per se did not influence the virologic response to DAAs, however, some factors played roles in affecting SVR among them.

The Severity of Depressive Symptoms as an Independent Predictor of Sustained Virological Response During Treatment of Hepatitis C With Pegylated Interferon-α2a and Oral Ribavirin.

BACKGROUND: Sustained virological response (SVR) is the best indicator of successful therapy for hepatitis C virus (HCV) infection. Patients with chronic HCV infection treated with pegylated interferon-α and ribavirin (PEG-IFN-α/RBV) can achieve SVR 56% of the time. OBJECTIVES: This study aimed to evaluate baseline predictors of SVR in patients treated with PEG-IFN-α/RBV for HCV chronic infection. METHODS: A total of 101 patients receiving PEG-IFN-α/RBV for chronic HCV infection participated in the prospective cohort study. Symptoms of depression were assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS) before the treatment. The multivariate regression analysis was applied to determine predictors of SVR. RESULTS: Of a total of 101 patients included, 99 patients reached the primary end point-24 weeks after completing treatment. After the initial analysis of probable predictive variables, the logistic analysis included age, sex, HCV genetic type, and MADRS score. The HCV genotype (odds ratio = 0.22 [confidence interval = 0.073-0.68, p = .008) and MADRS score (OR = 0.88 [confidence interval = 0.80-0.98), p = .013]) predicted an SVR outcome. CONCLUSIONS: The severity of depressive symptoms before treatment and HCV genotype are independent predictors of SVR.

Establishment of a novel minigenome system for the identification of drugs targeting Nipah virus replication.

Nipah virus (NiV) is a deadly zoonotic pathogen with high potential to cause another pandemic. Owing to biosafety concerns, studies on living NiV must be performed in biosafety level 4 (BSL-4) laboratories, which greatly hinders the development of anti-NiV drugs. To overcome this issue, minigenome systems have been developed to study viral replication and screen for antiviral drugs. This study aimed to develop two minigenome systems (transient and stable expression) based on a helper cell line expressing the NiV P, N and L proteins required to initiate NiV RNA replication. Stable minigenome cells were resistant to ribavirin, remdesivir and favipiravir but sensitive to interferons. Cells of the transient replication system were sensitive to ribavirin and favipiravir and suitable for drug screening. Our study demonstrates a feasible and effective platform for studying NiV replication and shows great potential for high-throughput drug screening in a BSL-2 laboratory environment.

A simplified molecularly imprinted ECL sensor based on Mn2SnO4 nanocubes for sensitive detection of ribavirin.

Conventional single-signal or emerging sandwich-type double-signal electrochemiluminescence (ECL) immunosensors/aptasensors have offered accurate detection of small molecules, yet suffer from complicated setup, long processing time, and non-reusability. Here, we demonstrate a simplified molecularly imprinted ECL sensor based on Mn2SnO4 nanocubes. As an n-type semiconductor, Mn2SnO4 has numerous active sites that can capture electrons to accelerate chemical reactions, resulting in enhanced ECL activity and stability. For the first time, we verify a robust cathodic ECL emission of Mn2SnO4 luminophores in the presence of K2S2O8 coreactants. The proposed ECL sensor applies to the sensitive detection of ribavirin (RBV), endowing a wide linear range (1-2000 ng mL-1), low detection limit (0.85 ng mL-1, S/N = 3), high stability, specificity, and reproducibility, and the detection capability in real milk and chicken samples. This work highlights single semiconductor luminophore-driven molecularly imprinted ECL sensors, meeting the original aspiration of uncomplicated but high-performance sensing in food safety inspection.

Treatment of the most difficult-to-cure hepatitis C virus-infected population with sofosbuvir / velpatasvir.

INTRODUCTION: Pangenotypic therapies for infections with hepatitis C virus (HCV), although universal and highly effective, entail a risk of treatment failure. OBJECTIVES: Our study aimed to identify the population of HCV­infected patients most difficult to cure with the sofosbuvir / velpatasvir (SOF/VEL) regimen. PATIENTS AND METHODS: The effectiveness of the SOF/VEL regimen with a possible addition of ribavirin (RBV) was evaluated in populations known to be less responsive to treatment, and then in a population characterized by the combination of all factors impairing effectiveness, comprising patients treated with this regimen in the EpiTer­2 multicenter retrospective study. RESULTS: A total of 2267 patients were treated with SOF/VEL±RBV. Of those, 2078 (96.4%) achieved sustained virologic response. The cure rate was 93.5% among 646 patients infected with genotype (GT) 3, 92.3% among 635 patients with cirrhosis, 95.5% in a population of 1233 men, and 94.1% among 421 patients with body mass index (BMI) above 30. An analysis in a group of 43 men with cirrhosis and obesity infected with GT3 showed the effectiveness of pangenotypic therapy at only 79.1%, falling to 66.7% in individuals with previous treatment failure. CONCLUSIONS: In a large population of SOF/VEL­treated HCV­infected patients, we showed relatively low effectiveness of the regimen in treatment­experienced men with cirrhosis and obesity, infected with GT3. Triple therapy should be considered when initiating the treatment of HCV infections in this group, which, however, needs to be confirmed in further studies. Previous studies were conducted in less demanding populations, because they did not take into account sex and BMI, which significantly affect the treatment effectiveness.

Hepatitis E virus infection of transplanted kidneys.

Immunocompromised patients are at risk of chronic hepatitis E (HEV) infection. Recurrent T cell and borderline rejections in a pediatric patient with high HEV copy numbers led us to study HEV infection within renal transplants. To investigate the frequency of renal HEV infection in transplanted patients, 15 samples from patients with contemporaneous diagnoses of HEV infection were identified at our center. Ten samples had sufficient residual paraffin tissue for immunofluorescence (IF) and RNA-fluorescence-in-situ-hybridization (RNA-FISH). The biopsy of the pediatric index patient was additionally sufficient for tissue polymerase chain reaction and electron microscopy. HEV RNA was detected in paraffin tissue of the index patient by tissue polymerase chain reaction. Subsequently, HEV infection was localized in tubular epithelial cells by IF, RNA-FISH, and electron microscopy. One additional biopsy from an adult was positive for HEV by RNA-FISH and IF. Focal IF positivity for HEV peptide was observed in 7 additional allografts. Ribavirin therapy was not successful in the pediatric index patient; after relapse, ribavirin is still administered. In the second patient, successful elimination of HEV was achieved after short-course ribavirin therapy. HEV infection is an important differential diagnosis for T cell rejection within transplanted kidneys. Immunostaining of HEV peptide does not necessarily prove acute infection. RNA-FISH seems to be a reliable method to localize HEV.