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https://www.readbyqxmd.com/read/29232582/discovery-and-evolution-of-aloperine-derivatives-as-a-new-family-of-hcv-inhibitors-with-novel-mechanism
#1
Xin Zhang, Xiao-Qin Lv, Sheng Tang, Lin Mei, Ying-Hong Li, Jing-Pu Zhang, Jian-Dong Jiang, Zong-Gen Peng, Dan-Qing Song
Aloperine (1), a Chinese natural product with a unique endocyclic scaffold, was first identified to be a potent hepatitis C virus (HCV) inhibitor in our laboratory. Thirty-four new aloperine derivatives were designed, synthesized and evaluated for their anti-HCV activities taking 1 as the lead. Among them, compound 7f exhibited the potential potency with EC50 values in a micromolar range against both wild-type and direct-acting antiviral agents (DAAs)-resistant variants, and synergistically inhibited HCV replication with approved DAAs...
December 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29229584/eliminating-hepatitis-c-within-low-income-countries-the-need-to-cure-genotypes-4-5-6
#2
REVIEW
Tarik Asselah, Tarek Hassanein, Imam Waked, Abdellah Mansouri, Geoffrey Dusheiko, Edward Gane
Around 70 to 100 million people are chronically infected with HCV worldwide. HCV anti-viral drug development has been remarkable and this revolution led to several direct-acting antiviral agents achieving an HCV cure after only 8-12 weeks of treatment duration. Drug development has focused first on HCV genotype 1 infection, since it was the most prevalent worldwide, although clinical trials included all genotypes prevalent in the US and Europe. Because the earliest in vitro assays utilised the GT 1b and 2 replicons, the initial classes of direct acting antivirals (protease inhibitors, non-nucleotide polymerase inhibitors) were genotype 1-specific, albiet had an effect on other less prevalent genotypes...
December 8, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/29228983/characterization-of-interactions-between-hepatitis-c-virus-ns5b-polymerase-annexin-a2-and-rna-effects-on-ns5b-catalysis-and-allosteric-inhibition
#3
Sara M Ø Solbak, Eldar Abdurakhmanov, Anni Vedeler, U Helena Danielson
BACKGROUND: Direct acting antivirals (DAAs) provide efficient hepatitis C virus (HCV) therapy and clearance for a majority of patients, but are not available or effective for all patients. They risk developing HCV-induced hepatocellular carcinoma (HCC), for which the mechanism remains obscure and therapy is missing. Annexin A2 (AnxA2) has been reported to co-precipitate with the non-structural (NS) HCV proteins NS5B and NS3/NS4A, indicating a role in HCC tumorigenesis and effect on DAA therapy...
December 11, 2017: Virology Journal
https://www.readbyqxmd.com/read/29228501/hcv-clearance-by-direct-acting-antiviral-treatments-reverses-insulin-resistance-in-chronic-hepatitis-c-patients
#4
Luigi E Adinolfi, Riccardo Nevola, Barbara Guerrera, Giovanni D'Alterio, Aldo Marrone, Mauro Giordano, Luca Rinaldi
BACKGROUND AND AIM: Chronic hepatitis C (HCV), particularly genotype 1, is associated with insulin resistance (IR) and diabetes. We evaluated the impact of HCV clearance by all-oral direct-acting antiviral (DAAs) treatments on IR and glycemic control. METHODS: Included in this prospective case-control study were 133 consecutive HCV-genotype 1 patients with advance liver fibrosis (F3-F4) without type 2 diabetes. Sixty-eight treated with DAAs and 65 untreated. Liver fibrosis was assessed by transient elastography...
December 11, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29226102/timing-of-hepatitis-c-virus-treatment-in-liver-transplant-candidates-in-the-era-of-direct-acting-antiviral-agents
#5
REVIEW
George Cholankeril, Mairin Joseph-Talreja, Brandon J Perumpail, Andy Liu, Eric R Yoo, Aijaz Ahmed, Aparna Goel
Chronic hepatitis C virus (HCV) infection remains the leading indication for liver transplantation (LT) in the United States. While most patients with chronic HCV infection remain asymptomatic, up to one-third develop progressive liver disease resulting in cirrhosis. LT is often the only curative treatment once significant hepatic decompensation develops. However, antiviral therapy for HCV infection has advanced markedly in the past 5 years with the discovery and approval of direct-acting antiviral agents. These new regimens are well tolerated, of short duration and highly effective, unlike the traditional treatment with pegylated-interferon and ribavirin...
December 28, 2017: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/29226099/efficacy-and-safety-of-direct-acting-antivirals-in-hepatitis-c-virus-infected-patients-taking-proton-pump-inhibitors
#6
Karn Wijarnpreecha, Supavit Chesdachai, Charat Thongprayoon, Veeravich Jaruvongvanich, Patompong Ungprasert, Wisit Cheungpasitporn
Background and Aims: Direct-acting antiviral (DAA) therapy is the cornerstone of the treatment of chronic hepatitis C virus (HCV) infection. Eradication of HCV, predicted by the attainment of a sustained virologic response (SVR) 12 weeks following DAA therapy, is the goal of this treatment. Interestingly, recent studies have reported the possible association between HCV-infected patients with DAA therapy concomitant use of proton pump inhibitors (PPIs) and lower odds of achieving SVR. This meta-analysis was conducted to summarize all available data and to estimate this potential association...
December 28, 2017: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/29225673/update-on-hepatitis-c-and-implications-for-pregnancy
#7
REVIEW
Jeffrey J Post
Mother-to-child transmission of hepatitis C virus infection occurs in a significant minority of cases and the diagnosis, treatment and cure of hepatitis C virus infection with direct acting antivirals prior to pregnancy can eliminate this risk in almost all cases. Women with hepatitis C virus infection have increased risks of adverse events in pregnancy and poor perinatal outcomes for their children, although the contribution of hepatitis C virus per se is difficult to determine. Altering the mode of delivery does not reduce mother to child transmission of hepatitis C virus infection, although avoidance of fetal scalp electrodes and other potential high risk procedures is recommended during pregnancy and delivery...
December 2017: Obstetric Medicine
https://www.readbyqxmd.com/read/29223371/planning-and-prioritizing-direct-acting-antivirals-treatment-for-hcv-patients-in-countries-with-limited-resources-lessons-from-the-egyptian-experience
#8
Aisha Elsharkawy, Maissa El Raziky, Wafaa El Akel, Kadry El Saeed, Rasha Eletreby, Mohamed Hassany, Manal Hamdy El-Sayed, Khaled Kabil, Sohier A Ismail, Magdy El-Serafy, Ashraf Omar Abdelaziz, Mohamed Kamal Shaker, Ayman Yosry, Wahid Doss, Yehia El Shazly, Gamal Esmat, Imam Waked
BACKGROUND AND AIM: The introduction of direct acting antivirals for HCV in Egypt led to massive treatment uptake to become the largest HCV treatment program worldwide. The aim of this paper is to present the Egyptian experience in planning and prioritizing mass treatment for HCV patients, highlighting the difficulties and limitations of the program as guide to other countries of similar limited resources. METHODS: Baseline data of 337,042 patients who started treatment from October 2014 to March 2016 were grouped into three equal time intervals of 6 months each...
December 6, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/29222916/transplanting-hcv-positive-livers-into-hcv-negative-patients-with-preemptive-antiviral-treatment-a-modeling-study
#9
Jagpreet Chhatwal, Sumeyye Samur, Emily D Bethea, Turgay Ayer, Fasiha Kanwal, Chin Hur, Mark S Roberts, Norah Terrault, Raymond T Chung
Under current guidelines hepatitis C virus (HCV)-positive livers are not transplanted into HCV-negative recipients because of adverse post-transplant outcomes associated with allograft HCV infection. However, HCV can now be cured post liver transplant (LT) using direct-acting antivirals (DAAs) with >90% success; therefore, HCV-negative patients on the liver transplant (LT) waiting list may benefit from accepting HCV-positive organs with preemptive treatment. Our objective was to evaluate if and in which HCV-negative patients the potential benefit of accepting an HCV-positive (i...
December 9, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29221500/analysis-of-naturally-occurring-resistance-associated-variants-to-ns3-4a-protein-inhibitors-ns5a-protein-inhibitors-and-ns5b-polymerase-inhibitors-in-patients-with-chronic-hepatitis-c
#10
Danhui Sun, Mingjia Dai, Shanshan Shen, Chunyang Li, Xuebing Yan
The first NS3/4A hepatitis C virus (HCV) protease inhibitors telaprevir and boceprevir were approved in 2011,and both NS5A and NS5B polymerase inhibitors were launched. Recently, direct-acting antivirals (DAAs) have had a major impact on patients infected with Hepatitis C virus (HCV). HCV DAAs are highly effective antivirals with fewer side effects. DAAs have been developed for treatment of HCV infection in combination with PEG-IFNα/RBV as well as in IFN-free regimens. However, some drug resistance mutations occur when a single oral DAA is used for treatment, which indicates that there is a low-frequency drug resistance mutation in HCV patients before the application of antiviral drugsOur research showed that natural resistance to HCV DAAs was found in treatment-naïve CHC patients and that the drug resistance mutation rates differ in various HCV genotypes...
December 8, 2017: Gene Expression
https://www.readbyqxmd.com/read/29219790/hepatitis-c-virus-infection-in-kidney-transplant-patients-current-treatment-options
#11
Pavlina Dzekova-Vidimliski, Aleksandar Sikole
Hepatitis C virus infection is highly prevalent among kidney transplant recipients, occurring consequently to their previous treatment with hemodialysis. Hepatitis C virus infection has been associated with lower graft and patient survival compared with that shown in patients without infection. The lower survival has been associated with the posttransplant progression of liver disease and increased risk for development of extrahepatic complications. The choice of immunosuppressive drugs could significantly affect the course of the infection with an accelerated viral replication after kidney transplant...
December 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/29217468/availability-of-hepatitis-c-diagnostics-and-therapeutics-in-european-and-eurasia-countries
#12
Hakan Leblebicioglu, Joop E Arends, Resat Ozaras, Giampaolo Corti, Lurdes Santos, Christoph Boesecke, Andrew Ustianowski, Ann-Sofi Duberg, Simona Ruta, Nermin N Salkic, Petr Husa, Ivana Lazarevic, Juan A Pineda, Natalia Yurievna Pshenichnaya, Tengiz Tsertswadze, Mojca Matičič, Edmond Puca, Gulzhan Abuova, Judit Gervain, Ramin Bayramli, Salih Ahmeti, Mairi Koulentaki, Badreddine Kilani, Adriana Vince, Francesco Negro, Mustafa Sunbul, Dominique Salmon
BACKGROUND: Treatment with direct acting antiviral agents (DAAs) has provided sustained virological response rates in >95% of patients with chronic hepatitis C virus (HCV) infection. However treatment is costly and market access, reimbursement and governmental restrictions differ among countries. We aimed to analyze these differences among European and Eurasian countries. METHODS: A survey including 20-item questionnaire was sent to experts in viral hepatitis...
December 4, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29212314/rapid-changes-in-serum-lipid-profiles-during-combination-therapy-with-daclatasvir-and-asunaprevir-in-patients-infected-with-hepatitis-c-virus-genotype-1b
#13
Takeshi Chida, Kazuhito Kawata, Kazuyoshi Ohta, Erika Matsunaga, Jun Ito, Shin Shimoyama, Satoru Yamazaki, Hidenao Noritake, Tetsuro Suzuki, Takafumi Suda, Yoshimasa Kobayashi
Background/Aims: Changes in lipid profiles in patients infected with hepatitis C virus (HCV) during direct-acting antiviral therapy have been reported in recent years. However, the clinical aspects of disturbed lipid metabolism in chronic HCV infection have not been fully elucidated. Methods: Dynamic changes in serum total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol and apolipoprotein levels in patients infected with HCV genotype 1b were examined during combination therapy with daclatasvir (DCV) and asunaprevir (ASV)...
December 8, 2017: Gut and Liver
https://www.readbyqxmd.com/read/29209282/identification-and-analysis-of-novel-inhibitors-against-ns3-helicase-and-ns5b-rna-dependent-rna-polymerase-from-hepatitis-c-virus-1b-con1
#14
Na Yang, Chaomin Sun, Lixin Zhang, Jianguo Liu, Fuhang Song
Hepatitis C virus (HCV) leads to severe liver diseases, including liver fibrosis, cirrhosis and hepatocellular carcinoma. Non-structural protein 3 helicase (NS3h) and non-structural protein 5B RNA-dependent RNA polymerase (NS5B) are involved in the replication of HCV RNA genome, and have been proved to be excellent targets for discovery of direct-acting antivirals. In this study, two high-throughput screening systems, fluorescence polarization (FP)-based ssDNA binding assay and fluorescence intensity (FI)-based dsRNA formation assay, were constructed to identify candidate NS3h and NS5B inhibitors, respectively...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29209223/timing-strategies-of-direct-acting-antivirals-and-biologics-administration-in-hcv-infected-subjects-with-inflammatory-bowel-diseases
#15
REVIEW
Nicola Imperatore, Fabiana Castiglione, Antonio Rispo, Anna Sessa, Nicola Caporaso, Filomena Morisco
Background: In the last years, inflammatory bowel disease (IBD) and hepatitis C virus (HCV) infection management has completely changed. However, the role of direct-acting antivirals (DAAs) and the correct timing of antiviral drugs administration in IBD patients needing biologics has not been evaluated. Objective: To discuss the management of HCV-infected IBD patients, focusing our attention on the timing of DAAs administration subjects needing biologics. Methods: Relevant articles addressing HCV management in patients needing biologics were identified by searching from PubMed, MEDLINE and Scopus...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29207613/changes-in-renal-function-indices-in-cirrhotic-chronic-hepatitis-c-patients-treated-with-sofosbuvir-containing-regimens
#16
Jianhong Chen, Xiaxia Zhang, Hao Luo, Chihong Wu, Min Yu, Dan Liu, Hongli Xi, Yihang Zhou, Yaoyu An, Xiaoyuan Xu
This study aimed to explore changes in hepatic and renal function indices in chronic hepatitis C (CHC) patients treated with direct-acting antivirals (DAAs). Forty-three CHC patients treated with sofosbuvir (SOF)-containing regimens were enrolled. At the end of treatment, the estimated glomerular filtration rate (eGFR) level was significantly decreased and the serum creatinine (Scr) and uric acid (UA) levels were significantly increased compared with baseline levels (eGFR: 86.7 ± 20.4 vs 80.5 ± 21.3, P01 = 0...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29206910/state-medicaid-hepatitis-c-treatment-eligibility-criteria-and-use-of-direct-acting-antivirals
#17
Shashi N Kapadia, Philip J Jeng, Bruce R Schackman, Yuhua Bao
Medicaid program criteria for accessing hepatitis C treatment are changing. Using Medicaid drug utilization data from 2014-6, we found that programs that have relaxed their criteria have seen significant increases in treatment utilization compared to those that have not. States with Medicaid expansions also had marked increases in utilization.
December 1, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29205441/hepatitis-c-transmission-from-seropositive-non-viremic-donors-to-non-hepatitis-c-liver-transplant-recipients
#18
Khurram Bari, Keith Luckett, Tiffany Kaiser, Tayyab Diwan, Madison Cuffy, Michael Schoech, Kamran Safdar, Jason T Blackard, Senu Apewokin, Flavio Paterno, Kenneth E Sherman, Stephen D Zucker, Nadeem Anwar, Shimul A Shah
Breakthroughs in Hepatitis C virus (HCV) treatment and rising rates of intravenous drug use have led to an increase in the number of organ donors that are HCV antibody positive but serum nucleic acid test (NAT) negative. The risk of HCV transmission from the liver grafts of these donors to recipients is unknown. To estimate the incidence of HCV transmission, we prospectively followed 26 consecutive HCV antibody (n=25) or NAT (n =1) negative transplant recipients who received a liver graft from donors that were HCV antibody positive but serum NAT negative between March 2016 and March 2017...
December 2, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29205416/the-short-term-incidence-of-hepatocellular-carcinoma-is-not-increased-after-hepatitis-c-treatment-with-direct-acting-antivirals-an-erchives-study
#19
Darrick K Li, Yanjie Ren, Daniel S Fierer, Stephanie Rutledge, Obaid S Shaikh, Vincent Lo Re, Tracey Simon, Abdul-Badi Abou-Samra, Raymond T Chung, Adeel A Butt
Recent studies have reported higher rates of hepatocellular carcinoma (HCC) in individuals treated with direct-acting antivirals (DAAs). However, making definitive conclusions has been challenging due to the heterogeneous populations and methodologies of these reports. We investigated whether DAA use is associated with higher rates of incident HCC compared to treatment with interferon-based regimens. We performed a retrospective population-based cohort study using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database...
December 2, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29205405/interferon-free-therapy-of-chronic-hepatitis-c-with-direct-acting-antivirals-does-not-change-the-short-term-risk-for-de-novo-hepatocellular-carcinoma-in-patients-with-liver-cirrhosis
#20
F Mettke, B Schlevogt, K Deterding, A Wranke, A Smith, K Port, M P Manns, A Vogel, M Cornberg, H Wedemeyer
BACKGROUND: Hepatitis C virus (HCV) clearance with IFN-based therapies reduces the incidence of hepatocellular carcinoma (HCC). There has been some debate if IFN-free therapy with direct-acting antivirals alters the risk for HCC. AIM: To investigate the HCC incidence in cirrhotic HCV patients who cleared HCV with direct-acting antivirals vs untreated controls. METHODS: We prospectively monitored 373 patients with chronic hepatitis C who received IFN-free therapies with direct-acting antiviral after January 2014...
December 4, 2017: Alimentary Pharmacology & Therapeutics
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