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Acta Medica Portuguesa May 2024Information about pan-genotypic treatments for hepatitis in Portugal is scarce. We aimed to evaluate the effectiveness and safety of glecaprevir plus pibrentasvir... (Observational Study)
Observational Study
INTRODUCTION
Information about pan-genotypic treatments for hepatitis in Portugal is scarce. We aimed to evaluate the effectiveness and safety of glecaprevir plus pibrentasvir (GLE/PIB) treatment for hepatitis C virus (HCV) infection in real-world clinical practice.
METHODS
An observational prospective study was implemented in six hospitals with 121 adult HCV patients who initiated treatment with GLE/PIB between October 2018 and April 2019, according to clinical practice. Eligible patients had confirmed HCV infection genotype (GT) 1 to 6 and were either treatment-naïve or had experience with interferon-, ribavirin- or sofosbuvir-based regimens, with or without compensated cirrhosis. Baseline sociodemographic and safety data are described for the total population (N = 115). Effectiveness [sustained virologic response 12 weeks after treatment (SVR12)] and patient-reported outcomes are presented for the core population with sufficient follow-up data (n = 97).
RESULTS
Most patients were male (83.5%), aged < 65 years (94.8%), with current or former alcohol consumption (77.3%), illicit drug use (72.6%), and HCV acquisition through intravenous drug use (62.0%). HIV co-infection occurred in 22.6% of patients. The prevalence of each GT was: GT1 51.3%, GT2 1.7%, GT3 30.4%, GT4 16.5%, and GT5.6 0%. Most patients were non-cirrhotic (80.9%) and treatment-naïve (93.8%). The SVR12 rates were 97.9% (95% CI: 92.8 - 99.4), and > 95% across cirrhosis status, GT, illicit drug use, alcohol consumption, and HCV treatment experience. The adverse event rate was 2.6%, and no patient discontinued treatment due to adverse events related to GLE/PIB.
CONCLUSION
Consistent with other real-world studies and clinical trials, treatment with GLE/PIB showed high effectiveness and tolerability overall and in difficult-to-treat subgroups (ClinicalTrials.gov: NCT03303599).
Topics: Humans; Male; Female; Benzimidazoles; Hepatitis C, Chronic; Middle Aged; Prospective Studies; Quinoxalines; Antiviral Agents; Sulfonamides; Pyrrolidines; Aged; Drug Combinations; Portugal; Sustained Virologic Response; Treatment Outcome; Adult; Leucine; Hepacivirus; Lactams, Macrocyclic; Aminoisobutyric Acids
PubMed: 38325411
DOI: 10.20344/amp.19178 -
Veterinarni Medicina Dec 2023Peste des petits ruminants virus (PPRV), a member of the family Paramyxoviridae, belongs to the genus Morbillivirus. It causes devastating viral diseases in small...
Peste des petits ruminants virus (PPRV), a member of the family Paramyxoviridae, belongs to the genus Morbillivirus. It causes devastating viral diseases in small ruminants and has been rapidly spreading over various regions in Africa, the Middle East, and Asia. Although vaccination is thought to be an effective management strategy against PPR infections, the heat sensitivity of PPRV vaccines severely restricts their use in regions with hot climates. In this research, we studied the antiviral activities of ribavirin and aimed to understand the potential mechanisms of action of ribavirin in the African green monkey kidney cells (Vero cells). In brief, the adsorption, intrusion, replication, and release of PPRV, as well as the mRNA expression level of RNA-dependent RNA polymerase (), were significantly inhibited in the ribavirin-treated Vero cells compared to those in the PPRV-infected cells that were not treated with ribavirin. Additionally, ribavirin has potential as an antiviral drug against PPRV, and its antiviral activity is mediated by the Janus kinase signal transducer and activator of transcription (JAK/STAT) and PI3K/AKT pathways.
PubMed: 38303996
DOI: 10.17221/56/2023-VETMED -
Frontiers in Pharmacology 2023Hepatitis C virus (HCV) infection is a significant global health concern, prompting the need for effective treatment strategies. This in-depth review critically assesses... (Review)
Review
Hepatitis C virus (HCV) infection is a significant global health concern, prompting the need for effective treatment strategies. This in-depth review critically assesses the landscape of HCV treatment, drawing parallels between traditional interferon/ribavirin therapy historically pivotal in HCV management and herbal approaches rooted in traditional and complementary medicine. Advancements in therapeutic development and enhanced clinical outcomes axis on a comprehensive understanding of the diverse HCV genome, its natural variations, pathogenesis, and the impact of dietary, social, environmental, and economic factors. A thorough analysis was conducted through reputable sources such as Science Direct, PubMed, Scopus, Web of Science, books, and dissertations. This review primarily focuses on the intricate nature of HCV genomes and explores the potential of botanical drugs in both preventing and treating HCV infections.
PubMed: 38283838
DOI: 10.3389/fphar.2023.1334160 -
Biosensors Dec 2023Amantadine (AMD) is an antiviral drug that is prohibited for use in livestock and poultry. In this study, carboxyl-modified magnetic nanoparticles (MNPs) were...
Amantadine (AMD) is an antiviral drug that is prohibited for use in livestock and poultry. In this study, carboxyl-modified magnetic nanoparticles (MNPs) were synthesized using the solvothermal method in one step with harmless and inexpensive regents, and they were used to label monoclonal antibodies (mAbs) of AMD in microwells with electrostatic adsorption. Then, a magnetic immunochromatography assay (MICA) method was successfully established. Under optimal conditions, the MICA showed a good performance, with a linear range of 0.2~10.0 µg/L. The limit of detection (LOD) was 0.068 µg/L with the instrument, and the visual LOD (vLOD) was 0.5 µg/L. There was no cross-reaction with rimantadine and ribavirin. The vLOD in real samples was 1.0 µg/kg. The developed MICA has the advantages of convenience, speed, and sensitivity, which make it suitable for the on-site rapid detection of AMD residues in chicken tissues and eggs.
Topics: Amantadine; Antiviral Agents; Chromatography, Affinity; Nanoparticles; Static Electricity
PubMed: 38248400
DOI: 10.3390/bios14010023 -
Revista Espanola de Quimioterapia :... Apr 2024Respiratory 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... (Review)
Review
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.
Topics: Infant; Humans; Child; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Antibodies, Monoclonal; Spain
PubMed: 38205560
DOI: 10.37201/req/147.2023 -
Clinical Pharmacology : Advances and... 2024The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a betacoronavirus responsible for the COVID-19 pandemic, causing respiratory disorders, and even... (Review)
Review
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a betacoronavirus responsible for the COVID-19 pandemic, causing respiratory disorders, and even death in some individuals, if not appropriately treated in time. To face the pandemic, preventive measures have been taken against contagions and the application of vaccines to prevent severe disease and death cases. For the COVID-19 treatment, antiviral, antiparasitic, anticoagulant and other drugs have been reused due to limited specific medicaments for the disease. Drug repurposing is an emerging strategy with therapies that have already tested safe in humans. One promising alternative for systematic experimental screening of a vast pool of compounds is computational drug repurposing (in silico assay). Using these tools, new uses for approved drugs such as chloroquine, hydroxychloroquine, ivermectin, zidovudine, ribavirin, lamivudine, remdesivir, lopinavir and tenofovir/emtricitabine have been conducted, showing effectiveness in vitro and in silico against SARS-CoV-2 and some of these, also in clinical trials. Additionally, therapeutic options have been sought in natural products (terpenoids, alkaloids, saponins and phenolics) with promising in vitro and in silico results for use in COVID-19 disease. Among these, the most studied are resveratrol, quercetin, hesperidin, curcumin, myricetin and betulinic acid, which were proposed as SARS-CoV-2 inhibitors. Among the drugs reused to control the SARS-CoV2, better results have been observed for remdesivir in hospitalized patients and outpatients. Regarding natural products, resveratrol, curcumin, and quercetin have demonstrated in vitro antiviral activity against SARS-CoV-2 and in vivo, a nebulized formulation has demonstrated to alleviate the respiratory symptoms of COVID-19. This review shows the evidence of drug repurposing efficacy and the potential use of natural products as a treatment for COVID-19. For this, a search was carried out in PubMed, SciELO and ScienceDirect databases for articles about drugs approved or under study and natural compounds recognized for their antiviral activity against SARS-CoV-2.
PubMed: 38197085
DOI: 10.2147/CPAA.S429064 -
World Journal of Virology Dec 2023Hepatitis E virus (HEV) is a small non-enveloped virus that is transmitted the fecal-oral route. It is a highly common cause of acute hepatitis, particularly in low to... (Review)
Review
Hepatitis E virus (HEV) is a small non-enveloped virus that is transmitted the fecal-oral route. It is a highly common cause of acute hepatitis, particularly in low to middle income regions of Asia, Africa, and Central America. Most cases are self-limited, and symptomatic patients usually present with acute icteric hepatitis. A subset of patients including pregnant women, older men, those with pre-existing liver disease and immunocompromised patients however, may develop severe disease and hepatic failure. Immunocompromised patients are also at risk for chronic infection, and their immunosuppression should be decreased in order to facilitate viral clearance. HEV can also present with a variety of extra-intestinal manifestations including neurological, renal, hematological, and pancreatic derangements. The gold standard of diagnosis is HEV ribonucleic acid detection nucleic acid amplification testing. Currently, there are no approved treatments for Hepatitis E, though ribavirin is the most commonly used agent to reduce viral load. Studies assessing the safety and efficacy of other antiviral agents for HEV are currently underway. HEV vaccination has been approved in China, and is currently being investigated in other regions as well. This review article aims to discuss the epidemiology, pathogenesis, presentation, diagnosis, complications, and treatment of Hepatitis E infection.
PubMed: 38187497
DOI: 10.5501/wjv.v12.i5.262 -
Health Science Reports Jan 2024Direct-acting antiviral agents (DAAs) have revolutionized the treatment of patients with chronic hepatitis C virus (HCV) infection, resulting in a high sustained...
BACKGROUND AND AIMS
Direct-acting antiviral agents (DAAs) have revolutionized the treatment of patients with chronic hepatitis C virus (HCV) infection, resulting in a high sustained virologic response (SVR) rate. However, the published data from the Eastern Province of Saudi Arabia are limited to small patient groups and specific DAAs used for patients with genotype-4.(GT-4). This study aimed to investigate the effectiveness and safety of DAAs for treating HCV infection in Saudi Arabia in a real-life setting.
METHODS
This retrospective study from January 2015 to December 2019 included all HCV-infected patients who received DAAs at a tertiary university hospital in Saudi Arabia. Baseline characteristics and laboratory data were collected from health records, including HCV RNA level, genotype, and presence of liver cirrhosis or steatosis. The primary outcome was undetectable HCV RNA at 12 weeks posttreatment (SVR12). Results were stratified based on different DAAs and HCV genotypes. Treatment-related adverse events were recorded. Statistical analyses were performed using SPSS version 25.0.
RESULTS
Of the 117 patients included, 43.2% had advanced fibrosis or cirrhosis, and the majority (90.6%) were treatment-naïve. The mean age was 50.1 ± 15.5 years, with 57.3% females. The most common genotype was GT-4 (44.4%), followed by GT-1 (40.2%). Most patients (64.3%) received sofosbuvir and daclatasvir ± ribavirin, while the remaining patients received various DAAs. Overall, 98.3% of the patients achieved SVR12. The therapy was well tolerated, with fatigue and headache being the most common side effects.
CONCLUSIONS
Treatment with DAAs is highly effective across different genotypes and various DDA regimens in the real world for treating HCV infection in the Eastern Province of Saudi Arabia, contributing to improved patient outcomes and the overall goal of HCV elimination.
PubMed: 38186940
DOI: 10.1002/hsr2.1795 -
The American Journal of Managed Care Dec 2023To estimate the comprehensive value of direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) compared with peginterferon alfa and ribavirin...
OBJECTIVES
To estimate the comprehensive value of direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) compared with peginterferon alfa and ribavirin (PEG/riba) employing a generalized cost-effectiveness analysis (GCEA).
STUDY DESIGN
To assess the societal-level cost-effectiveness of DAA treatment for HCV, we extended a previously published discrete-time Markov simulation model of HCV transmission and progression to include market dynamics and broader elements of value.
METHODS
We followed a stepwise process to add novel value elements to a traditional CEA model for HCV treatments. For each additional element of value, we estimated incremental cost-effectiveness ratios (ICERs) of DAAs compared with PEG/riba.
RESULTS
The health technology assessment (HTA)-style model yielded an ICER value of $64,512 per quality-adjusted life-year (QALY). Adding transmission dynamics resulted in an ICER value of $52,971 per QALY, whereas accounting for transmission dynamics and dynamic price and efficacy further decreased ICER values by 90% to $6406 per QALY. Incorporating genericization, productivity loss, caregiver spillover, and differential valuations of LYs vs quality of life, disease severity, and insurance value further decreased the ICER value to $4487 per QALY, a 93% reduction from the baseline HTA-style CEA to the fully realized GCEA.
CONCLUSIONS
Our GCEA study results confirm that DAAs are a cost-effective treatment for HCV compared with PEG/riba even when using conventional cost-effectiveness approaches. Incorporating broader elements of value resulted in more than a 10-fold improvement in cost-effectiveness, emphasizing the substantive impact of a generalized approach and the importance of incorporating GCEAs into decision-making.
Topics: Humans; Antiviral Agents; Hepacivirus; Cost-Effectiveness Analysis; Quality of Life; Hepatitis C, Chronic; Cost-Benefit Analysis; Ribavirin; Quality-Adjusted Life Years; Hepatitis C
PubMed: 38170486
DOI: 10.37765/ajmc.2023.89468 -
Polish Archives of Internal Medicine Feb 2024Pangenotypic therapies for infections with hepatitis C virus (HCV), although universal and highly effective, entail a risk of treatment failure.
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 HCV‑infected 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 EpiTer‑2 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/VEL‑treated HCV‑infected patients, we showed relatively low effectiveness of the regimen in treatment‑experienced 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.
Topics: Male; Humans; Sofosbuvir; Hepacivirus; Antiviral Agents; Retrospective Studies; Hepatitis C; Ribavirin; Treatment Outcome; Liver Cirrhosis; Obesity; Benzimidazoles; Benzopyrans; Carbamates; Heterocyclic Compounds, 4 or More Rings
PubMed: 38164647
DOI: 10.20452/pamw.16644