Intracellular metabolism and potential cardiotoxicity of a β-D-2'-C-methyl-2,6-diaminopurine ribonucleoside phosphoramidate that inhibits hepatitis C virus replication.

Intracellular metabolism and potential cardiotoxicity of a β-D-2'-C-methyl-2,6-diaminopurine ribonucleoside phosphoramidate that inhibits hepatitis C virus replication. Nucleosides Nucleotides Nucleic Acids. 2019 Oct 09;:1-21 Authors: Tao S, Zhou L, Zhang H, Zhou S, Amiralaei S, Shelton J, Ehteshami M, Jiang Y, Amblard F, Coats SJ, Schinazi RF Abstract β-D-2'-C-Methyl-2,6-diaminopurine ribonucleoside (2'-C-Me-DAPN) phosphoramidate prodrug (DAPN-PD) is a selective hepatitis C virus inhibitor that is metabolized intracellularly into two active metabolites: 2'-C-Methyl-DAPN triphosphate (2'-C-Me-DAPN-TP) and 2'-C-methyl-guanosine 5'-triphosphate (2'-C-Me-GTP). BMS-986094 and IDX-184 are also bioconverted to 2'-C-Me-GTP. A phase IIb clinical trial with BMS-986094 was abruptly halted due to adverse cardiac and renal effects. Herein, we developed an efficient large scale synthesis of DAPN-PD and determined intracellular pharmacology of DAPN-PD in comparison with BMS-986094 and IDX-184, versus Huh-7, HepG2 and interspecies primary hepatocytes and human cardiomyocytes. Imaging data of drug treated human cardiomyocytes was found to be most useful in determining toxicity potential as no obvious beating rate change was observed for IDX-184 up to 50 µM up at 48 h. However, with BMS-986094 and DAPN-PD at 10 µM changes to both beat rate and rhythm were noted. PMID: 31595843 [PubMed - as supplied by publisher]
Source: Nucleosides, Nucleotides and Nucleic Acids - Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

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CONCLUSIONS: At the time the HEPLA study was carried out, the data from this cross-section of patients in Latin America showed that the CHC population has variation in disease and viral characteristics, with a minority of patients receiving treatment and many patients having advanced disease. Increased awareness and access to treatment are necessary in Latin America in order to meet the goal of hepatitis C virus elimination by 2030. PMID: 31718995 [PubMed - as supplied by publisher]
Source: Annals of Hepatology - Category: Gastroenterology Tags: Ann Hepatol Source Type: research
ConclusionsThe SVR is high within BCLC B HCV-HCC patients by DAAs treatment. The risk of HCC recurrence and progression is not increased by DAAs.
Source: Journal of Microbiology, Immunology and Infection - Category: Microbiology Source Type: research
AbstractOver the last decade, genome-wide association studies led to major advances in identifying human genetic variants associated with infectious disease susceptibility. On the pathogen side, comparable methods are now applied to identify disease-modulating pathogen variants. As host and pathogen variants jointly determine disease outcomes, the most recent development has been to explore simultaneously host and pathogen genomes, through so-called genome-to-genome studies. In this review, we provide some background on the development of genome-to-genome analysis and we detail the first wave of studies in this emerging fi...
Source: Human Genetics - Category: Genetics & Stem Cells Source Type: research
The scheme will run in Newcastle and offer an incentive for needle users, who are at high risk of contracting the infectious virus from dirty syringes, to get a blood test at their local pharmacy.
Source: the Mail online | Health - Category: Consumer Health News Source Type: news
CONCLUSIONS: This study confirms the higher rate of risk behaviors and the levels of impulsiveness commonly observed in patients with HCV, along with comparisons to patients with HTLV-1. PMID: 31711914 [PubMed - as supplied by publisher]
Source: Annals of Hepatology - Category: Gastroenterology Tags: Ann Hepatol Source Type: research
We present a narrative review of HCC in Africa, discussing present and future trends. [...] Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.Article in Thieme eJournals: Table of contents  |  Abstract  |  Full text
Source: Seminars in Liver Disease - Category: Gastroenterology Authors: Tags: Review Article Source Type: research
The advent of direct-acting antivirals (DAAs) has revealed high rates of sustained virological response at 12 weeks (SVR 12) in Hepatitis C (HCV) treatment. Since the introduction of DAAs, in our centre, 42% of patients treated for HCV are HIV co-infected. Our study aimed to identify the SVR 12 rates between this group and HCV mono-infected patients.
Source: Journal of Infection - Category: Infectious Diseases Authors: Tags: Letter to the Editor Source Type: research
This large community-based educate, test and treat programme in more than 200,000 villagers demonstrates the feasibility and effectiveness of this model for elimination of HCV infection in rural communities. We estimate treatment coverage and cure of 84.6% of the estimated 17137 infected persons aged 12-80 years across the 73 villages.
Source: Journal of Hepatology - Category: Gastroenterology Authors: Source Type: research
Substance misuse and needle exchange patients in Newcastle will be given  “up to £25 of Greggs vouchers” if they present for a blood spot test for hepatitis C in a community pharmacy.
Source: The Pharmaceutical Journal - Category: Drugs & Pharmacology Source Type: research
AbstractBackground and AimsThe features of non-viral, nonalcohol hepatocellular carcinoma (NBNC-HCC) remain elusive. The aim of this study was to investigate this clinical characteristics and overall survival of NBNC-HCC compared to hepatitis B- (HBV-HCC) and hepatitis C-related (HCV-HCC) HCC.MethodsWe analyzed the etiologies, fibrosis stages, clinical data, and outcomes of newly diagnosed patients with HCC.ResultsA total of 1777 HCC patients were recruited, including 332 patients with NBNC-HCC, 682 patients with HBV-HCC, 680 patients with HCV-HCC, and 83 patients with HBV/HCV HCC. Patients with NBNC-HCC were older (69.9 &...
Source: Digestive Diseases and Sciences - Category: Gastroenterology Source Type: research
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