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https://www.readbyqxmd.com/read/29353349/daclatasvir-a-review-of-preclinical-and-clinical-pharmacokinetics
#1
REVIEW
Yash Gandhi, Timothy Eley, Aberra Fura, Wenying Li, Richard J Bertz, Tushar Garimella
Daclatasvir is a first-in-class, highly selective, hepatitis C virus, non-structural protein 5a polymerase replication complex inhibitor with picomolar potency and broad genotypic coverage in vitro. Daclatasvir undergoes rapid absorption, with a time to reach maximum plasma concentration of 1-2 h and an elimination half-life of ~ 10 to 14 h observed in single-ascending dose studies. Steady state was achieved by day 4 in multiple-ascending dose studies. Daclatasvir can be administered without regard to food or pH modifiers...
January 20, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29352420/diagnosis-and-management-of-hepatitis-c-infection-in-primary-care-settings
#2
Debra Guss, Jagannath Sherigar, Paul Rosen, Smruti R Mohanty
Hepatitis C virus (HCV) infection is a significant health problem worldwide, and is the leading cause of cirrhosis, hepatocellular carcinoma, and liver transplantation in the United States. The management of HCV has changed significantly over the last 5 years, as treatments have become simpler and more efficacious. Medication efficacy is now greater than 90%, with a high barrier to resistance and few side effects. This review is a collaboration between primary care and hepatology providers to explore all aspects of HCV management: acute versus chronic HCV infection, transmission and testing, and diagnosis and treatment...
January 19, 2018: Journal of General Internal Medicine
https://www.readbyqxmd.com/read/29352135/blocking-zika-virus-vertical-transmission
#3
Pinar Mesci, Angela Macia, Spencer M Moore, Sergey A Shiryaev, Antonella Pinto, Chun-Teng Huang, Leon Tejwani, Isabella R Fernandes, Nicole A Suarez, Matthew J Kolar, Sandro Montefusco, Scott C Rosenberg, Roberto H Herai, Fernanda R Cugola, Fabiele B Russo, Nicholas Sheets, Alan Saghatelian, Sujan Shresta, Jeremiah D Momper, Jair L Siqueira-Neto, Kevin D Corbett, Patricia C B Beltrão-Braga, Alexey V Terskikh, Alysson R Muotri
The outbreak of the Zika virus (ZIKV) has been associated with increased incidence of congenital malformations. Although recent efforts have focused on vaccine development, treatments for infected individuals are needed urgently. Sofosbuvir (SOF), an FDA-approved nucleotide analog inhibitor of the Hepatitis C (HCV) RNA-dependent RNA polymerase (RdRp) was recently shown to be protective against ZIKV both in vitro and in vivo. Here, we show that SOF protected human neural progenitor cells (NPC) and 3D neurospheres from ZIKV infection-mediated cell death and importantly restored the antiviral immune response in NPCs...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29351766/efficacy-and-safety-of-sofosbuvir-containing-regimens-in-patients-co-infected-with-chronic-hepatitis-c-virus-and-human-immunodeficiency-virus-a-meta-analysis
#4
Guotao Li, Ke Zang, Guoqiang Zhang, Danyan Zhu, Xiaozhao Deng
BACKGROUND: The treatment of hepatitis C virus (HCV) in HCV/human immunodeficiency virus (HIV) co-infected patients remains complex. This present meta-analysis evaluated the efficacy and safety of Sofosbuvir (SOF) for treatment in HCV/HIV co-infected patients using the most recent and available data. METHODS: A systematic search of the published data was conducted in PubMed Medline, EMBASE and Cochrane databases. Eligible studies were clinical trials, case-control studies or prospective cohort studies aiming at assessing the efficacy and safety of the SOF-containing regimens in patients co-infected with HCV and HIV...
January 19, 2018: Virology Journal
https://www.readbyqxmd.com/read/29351151/hepatitis-c-in-pregnancy-in-the-era-of-direct-acting-antiviral-treatment-potential-benefits-of-universal-screening-and-antepartum-therapy
#5
Helene B Bernstein, Jeffrey C Dunkelberg, Kimberly K Leslie
Hepatitis C in pregnancy is on the rise, and new direct-acting antiviral agents are available that cure the disease. Published recommendations need to be reviewed and clinically evaluated for the care of pregnant women who are at risk for or have chronic hepatitis C. Available evidence and some of the medical and ethical reasons to consider universal screening and antepartum therapy for hepatitis C during pregnancy are presented. Universal screening and proactive treatment during pregnancy is on the horizon, and these measures should be quickly evaluated for safety and implemented if appropriate...
March 2018: Clinical Obstetrics and Gynecology
https://www.readbyqxmd.com/read/29350417/hepatitis-c-virus-core-protein-induces-dysfunction-of-liver-sinusoidal-endothelial-cell-by-down-regulation-of-silent-information-regulator-1
#6
Li-Jie Sun, Jian-Wu Yu, Yu-Guang Shi, Xiao-Yu Zhang, Meng-Ni Shu, Mo-Yang Chen
Objective Hepatic fibrosis is a frequent feature of chronic hepatitis C virus (HCV) infection. Some evidence has suggested the potential role of silent information regulator 1 (SIRT1) in organ fibrosis. The aim of this study was to investigate the effect of HCV core protein on expression of SIRT1 of liver sinusoidal endothelial cell (LSEC) and function of LSEC. Methods LSECs were co-cultured with HepG2 cells or HepG2 cells expressing HCV core protein and LSECs cultured alone were used as controls. After co-culture, the activity and expression levels of mRNA and protein of SIRT1 in LSEC were detected by a SIRT1 fluorometric assay kit, real time-PCR (RT-PCR), Western blot, respectively...
January 19, 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/29350402/effectiveness-and-safety-of-original-and-generic-sofosbuvir-for-the-treatment-of-chronic-hepatitis-c-a-real-world-study
#7
Sebastián Marciano, Leila Haddad, María Virginia Reggiardo, Mirta Peralta, Cecilia Vistarini, Mónica Marino, Valeria Inés Descalzi, Claudia D'Amico, Sebastián Figueroa Escuti, Luis Alejandro Gaite, Roberto Pérez Ravier, Cristina Longo, Silvia Mabel Borzi, Omar Andrés Galdame, Fernando Bessone, Hugo Alberto Fainboim, Silvia Frías, Mariano Cartier, Adrián Carlos Gadano
We report the first real-world prospective multicenter cohort study that evaluated the effectiveness and safety of original or generic sofosbuvir-based regimens in patients with chronic hepatitis C in Latin America. The main endpoints were assessment of sustained virological response and serious adverse events rates. A total of 321 patients with chronic hepatitis C treated with the following regimens were included: sofosbuvir plus daclatasvir for 12 (n = 34) or 24 (n = 135) weeks, sofosbuvir plus daclatasvir plus ribavirin for 12 (n = 84) or 24 (n = 56) weeks, or sofosbuvir plus ribavirin for 12 (n = 8) or 24 (n = 2) weeks...
January 19, 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/29349793/the-effectiveness-and-safety-of-ledipasvir-plus-sofosbuvir-in-adolescents-with-chronic-hepatitis-c-virus-genotype-4-infection-a-real-world-experience
#8
H R El-Khayat, E M Kamal, M H El-Sayed, M El-Shabrawi, H Ayoub, A RizK, M Maher, R Y El Sheemy, Y M Fouad, D Attia
BACKGROUND: The combination of ledipasvir plus sofosbuvir was recently approved for treatment of adolescent (12-17 years) HCV genotype 1, 4, 5 & 6 patients. However, few clinical trials have been performed in genotype 1 patients. AIM: To investigate the effectiveness and safety of ledipasvir plus sofosbuvir in chronic HCV adolescent patients with genotype 4 in the real world. METHODS: This prospective multicentre (six centres) open-label study included 144 adolescent chronic HCV patients with genotype 4 (mean age 14 ± 2, 69% males)...
January 19, 2018: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29345847/characterizing-the-temporal-evolution-of-the-hepatitis-c-virus-epidemic-in-pakistan
#9
Houssein H Ayoub, Zaina Al Kanaani, Laith J Abu-Raddad
Pakistan has the second largest number of hepatitis C virus (HCV) infections in the world. We assessed past, present, and future levels and trends of the HCV epidemic in Pakistan. An age-structured mathematical model was developed and analyzed to describe transmission dynamics over 1980-2050. The model was fitted to a nationally-representative survey and a comprehensive database of systematically-gathered HCV antibody (Ab) prevalence data. HCV Ab and chronic infection prevalences peaked at 5.3% and 3.9% in 2000, but were projected to decline to 4...
January 18, 2018: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29345515/safety-of-biologic-agents-for-psoriasis-in-patients-with-viral-hepatitis
#10
Nawaf AlMutairi, Hesham Alaadin Abouzaid
INTRODUCTION: Biologics are highly effective, important treatment options for moderate-to-severe psoriasis. Biologics are well tolerated and have few side effects. However, the use of biologics in patients with concomitant chronic viral hepatitis is debatable. Recent reports have suggested a very low associated risk of reactivation of chronic hepatitis B (HBV) and C (HCB). OBJECTIVE: To evaluate the safety and effectiveness of biologics for moderate to severe psoriasis patients with concomitant chronic viral hepatitis...
January 18, 2018: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/29344726/the-safety-and-efficacy-of-elbasvir-and-grazoprevir-in-participants-with-hepatitis-c-virus-genotype-1b-infection
#11
Stefan Zeuzem, Lawrence Serfaty, John Vierling, Wendy Cheng, Jacob George, Jan Sperl, Simone Strasser, Hiromitsu Kumada, Peggy Hwang, Michael Robertson, Janice Wahl, Eliav Barr, Rohit Talwani, Heather Platt
BACKGROUND: Genotype 1b (GT1b) is the most common subtype of the hepatitis C virus (HCV). We present an integrated analysis of 1070 participants with HCV GT1b infection from 30 countries who received elbasvir/grazoprevir for 12 weeks. METHODS: This is a retrospective analysis of data from participants with chronic HCV GT1b infection enrolled in 11 phase II/III clinical trials. All participants received elbasvir 50 mg plus grazoprevir 100 mg once daily for 12 weeks...
January 17, 2018: Journal of Gastroenterology
https://www.readbyqxmd.com/read/29343250/evaluation-of-health-status-in-patients-with-hepatitis-c-treated-with-and-without-interferon
#12
R Ragusa, G Bertino, A Bruno, E Frazzetto, F Cicciu, G Giorgianni, L Lupo
BACKGROUND: The evolution of technology in healthcare has increased the health care's costs and, the universal healthcare systems, in developed countries, need to ensure proper allocation of resources. Thus, the major issue is assessing the effectiveness of new medical technologies. The evaluation of quality of life in response to new treatments has become a key indicator in chronic conditions for which medical interventions are evaluated not only in terms of increasing the number of expected life years but also in terms of increasing quality of life...
January 17, 2018: Health and Quality of Life Outcomes
https://www.readbyqxmd.com/read/29340806/distribution-of-il28b-and-il10-polymorphisms-as-genetic-predictors-of-treatment-response-in-pakistani-hcv-genotype-3-patients
#13
Humaira Naeemi, Rabia Aslam, Syed Mohsin Raza, Muhammad Aiman Shahzad, Shagufta Naz, Sobia Manzoor, Saba Khaliq
There are over 10 million hepatitis C virus (HCV)-infected patients in Pakistan. For these patients, a combination of interferon with ribavirin is the most economical and easily available treatment. Single-nucleotide polymorphisms in interleukin genes have been reported to be associated with the pathogenesis and clearance of HCV, and sustained virologic response (SVR). An interleukin 28B (IL28B) gene polymorphism has been shown to modify treatment outcomes, but the effects of interleukin 10 (IL10) polymorphisms have not been previously assessed in the Pakistani population...
January 16, 2018: Archives of Virology
https://www.readbyqxmd.com/read/29340553/hepatocellular-carcinoma-diagnosis-and-operative-management
#14
Marcio F Chedid, Cleber R P Kruel, Marcelo A Pinto, Tomaz J M Grezzana-Filho, Ian Leipnitz, Cleber D P Kruel, Leandro A Scaffaro, Aljamir D Chedid
INTRODUCTION: Hepatocellular carcinoma is an aggressive malignant tumor with high lethality. AIM: To review diagnosis and management of hepatocellular carcinoma. METHODS: Literature review using web databases Medline/PubMed. RESULTS: Hepatocellular carcinoma is a common complication of hepatic cirrhosis. Chronic viral hepatitis B and C also constitute as risk factors for its development. In patients with cirrhosis, hepatocelular carcinoma usually rises upon malignant transformation of a dysplastic regenerative nodule...
October 2017: Arquivos Brasileiros de Cirurgia Digestiva: ABCD, Brazilian Archives of Digestive Surgery
https://www.readbyqxmd.com/read/29339926/using-a-chronic-hepatitis-b-registry-to-support-population-level-liver-cancer-prevention-in-sydney-australia
#15
Monica C Robotin, Ximena Masgoret, Mamta Porwal, David Goldsbury, Chee Khoo, Jacob George
Background: Approximately 1% of Australians have chronic hepatitis B (CHB), which disproportionately affects people born in hepatitis B-endemic countries. Currently, approximately half of the people affected remain undiagnosed and antiviral treatment uptake is suboptimal (~5%). This increases the likelihood of developing end-stage disease complications, particularly hepatocellular cancer (HCC), and largely accounts for the significant increases in HCC incidence and mortality in Australia over the last decades...
2018: Clinical Epidemiology
https://www.readbyqxmd.com/read/29338702/estimating-the-scale-of-chronic-hepatitis-c-virus-infection-in-the-eu-eea-a-focus-on-migrants-from-anti-hcv-endemic-countries
#16
A M Falla, A A Ahmad, E Duffell, T Noori, I K Veldhuijzen
BACKGROUND: Increasing the proportion diagnosed with and on treatment for chronic hepatitis C (CHC) is key to the elimination of hepatitis C in Europe. This study contributes to secondary prevention planning in the European Union/European Economic Area (EU/EEA) by estimating the number of CHC (anti-HCV positive and viraemic) cases among migrants living in the EU/EEA and born in endemic countries, defining the most affected migrant populations, and assessing whether country of birth prevalence is a reliable proxy for migrant prevalence...
January 16, 2018: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29337905/the-role-of-mirnas-in-the-pathophysiology-of-liver-diseases-and-toxicity
#17
REVIEW
Florian Schueller, Sanchari Roy, Mihael Vucur, Christian Trautwein, Tom Luedde, Christoph Roderburg
Both acute and chronic liver toxicity represents a major global health burden and an important cause of morbidity and lethality worldwide. Despite epochal progress in the treatment of hepatitis C virus infections, pharmacological treatment strategies for most liver diseases are still limited and new targets for prevention or treatment of liver disease are urgently needed. MicroRNAs (miRNAs) represent a new class of highly conserved small non-coding RNAs that are involved in the regulation of gene expression by targeting whole networks of so called "targets"...
January 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29337848/identifying-pre-existing-ns3-and-ns5a-resistance-associated-variants-and-transmission-chains-in-the-polish-hiv-hcv-genotype-1-epidemic-impact-on-prevention-and-treatment
#18
Miłosz Parczewski, Iwona Cielniak, Justyna Kordek, Bogusz Aksak-Wąs, Anna Urbańska, Magdalena Leszczyszyn-Pynka, Ewa Siwak, Monika Bociąga-Jasik, Anna Nowak, Aleksandra Szymczak, Małgorzata Zalewska, Władysław Łojewski, Anne-Mieke Vandamme, Nadine Lübke, Lize Cuypers
BACKGROUND: Hepatitis C virus (HCV) resistance-associated variants (RAVs) have been shown to adversely affect treatment response of direct-acting antivirals (DAAs). Identifying pre-existing RAVs and transmission networks among HIV/HCV genotype 1 (G1) infected patients from Poland will assist in shaping surveillance strategies for HCV. METHODS: NS3 and NS5A sequences were obtained from samples of 112 DAA-naive G1 patients (45 G1a, 67 G1b), of which 74 were chronically infected and 38 were diagnosed with acute hepatitis C (AHC)...
January 15, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29335738/remission-of-psoriasis-after-treatment-of-chronic-hepatitis-c-virus-infection-with-direct-acting-antivirals
#19
Masaru Enomoto, Chiharu Tateishi, Daisuke Tsuruta, Akihiro Tamori, Norifumi Kawada
No abstract text is available yet for this article.
January 16, 2018: Annals of Internal Medicine
https://www.readbyqxmd.com/read/29334550/chronic-hepatitis-c-virus-infection-and-subsequent-hiv-viral-load-among-women-with-hiv-initiating-antiretroviral-therapy
#20
Sarah J Willis, Stephen R Cole, Daniel Westreich, Andrew Edmonds, Christopher B Hurt, Svenja Albrecht, Kathryn Anastos, Michael Augenbraun, Margaret Fischl, Audrey L French, Aley G Kalapila, Roksana Karim, Marion G Peters, Michael Plankey, Eric C Seaberg, Phyllis C Tien, Adaora A Adimora
OBJECTIVE(S): One in four persons living with HIV is coinfected with HCV. Biological and behavioral mechanisms may increase HIV viral load among coinfected persons. Therefore, we estimated the longitudinal effect of chronic HCV on HIV suppression after ART initiation among women with HIV (WWH). DESIGN: HIV RNA was measured every six months among 441 WWH in the Women's Interagency HIV Study who initiated ART from 2000-2015. METHODS: Log-binomial regression models were used to compare the proportion of study visits with detectable HIV RNA between women with and without chronic HCV...
January 13, 2018: AIDS
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