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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
#1
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/29346834/twelve-week-ravidasvir-plus-ritonavir-boosted-danoprevir-and-ribavirin-for-non-cirrhotic-hcv-genotype-1-patients-a-phase-2-study
#2
Jia-Horng Kao, Min-Lung Yu, Chi-Yi Chen, Cheng-Yuan Peng, Ming-Yao Chen, Huoling Tang, Qiaoqiao Chen, Jinzi J Wu
BACKGROUND AND AIM: The need for all-oral HCV treatments with higher response rates, improved tolerability and lower pill burden compared to interferon-inclusive regimen has led to the development of new direct-acting antiviral agents (DAAs). Ravidasvir (RDV) is a second-generation, pan-genotypic NS5A inhibitor with high barrier to resistance. The aim of this phase 2 study (EVERST study) was to assess the efficacy and safety of interferon-free, 12-week RDV plus ritonavir-boosted danoprevir (DNVr) and ribavirin (RBV) regimen for treatment-naïve Asian HCV genotype 1 (GT1) patients without cirrhosis...
January 18, 2018: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29345407/hepatitis-c-eradication-with-daa-and-risk-of-liver-cancer-recurrence-the-debate-unrests
#3
Massimo Colombo, Vincenzo Boccaccio
The advent of user friendly and highly successful oral regimens based on direct antiviral agents (DAA), has made a cure of hepatitis C possible in more than 95% of treated patients, including those who were considered difficult to cure with interferon, a vast category including patients with advanced liver disease and those who had a hepatocellular carcinoma (HCC) successfully eradicated by resection or local ablation1 . Despite low rates of treatment uptake and response to therapy with interferon, such hard to treat patients were able to gain significant health benefits, like halting of progression towards liver failure and prevention of second primary tumours, once replication of the hepatitis C virus (HCV) was permanently shut down2,3 ...
January 18, 2018: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29343250/evaluation-of-health-status-in-patients-with-hepatitis-c-treated-with-and-without-interferon
#4
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/29339810/extrahepatic-cancers-and-chronic-hcv-infection
#5
REVIEW
Stanislas Pol, Anaïs Vallet-Pichard, Olivier Hermine
Infectious agents, such as HCV, account for ∼15% of human cancers. HCV infects not only hepatocytes but also extrahepatic cells. Chronic HCV infection can induce chronic inflammation with qualitative and quantitative alterations of the immune repertoire and tissue microenvironment, which could induce various neoplasias. Epidemiological studies and meta-analyses suggest an increased rate of extrahepatic cancers in patients with chronic HCV infection along with a higher risk of intrahepatic cholangiocarcinoma, pancreatic cancer and non-Hodgkin lymphoma (NHL), highlighting the need to screen for HCV infection in patients with these cancers...
January 17, 2018: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29334502/risk-of-hepatitis-b-virus-reactivation-among-patients-treated-with-ledipasvir-sofosbuvir-for-hepatitis-c-virus-infection
#6
Beshoy T Yanny, Nyan L Latt, Sammy Saab, Steven Han, Gina Choi, Jason Kramer, Amandeep K Sahota
BACKGROUND: Direct acting antiviral (DAA) agents are the standard of care for treatment of hepatitis C virus (HCV)-infected individuals. Hepatitis B virus (HBV) reactivation during HCV treatment has been reported, the incidence and clinical outcome remains unclear. The aim of our study is to examine the risk of HBV reactivation in actively infected or previously exposed patients during or after HCV treatment with DAAs. METHODS: Adults with chronic HCV infection previously exposed or actively infected with HBV and treated with DAAs between December 2015 to 2016 were included...
January 12, 2018: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/29325885/9-aminoacridine-based-agents-impair-the-bovine-viral-diarrhea-virus-bvdv-replication-targeting-the-rna-dependent-rna-polymerase-rdrp
#7
Roberta Loddo, Valeria Francesconi, Erik Laurini, Silvia Boccardo, Suzana Aulic, Maurizio Fermeglia, Sabrina Pricl, Michele Tonelli
Bovine viral diarrhea virus (BVDV) infection is still a plague that causes important livestock pandemics. Despite the availability of vaccines against BVDV, and the implementation of massive eradication or control programs, this virus still constitutes a serious agronomic burden. Therefore, the alternative approach to combat Pestivirus infections, based on the development of antiviral agents that specifically inhibit the replication of these viruses, is of preeminent actuality and importance. Capitalizing from a long-standing experience in antiviral drug design and development, in this work we present and characterize a series of small molecules based on the 9-aminoacridine scaffold that exhibit potent anti-BVDV activity coupled with low cytotoxicity...
January 4, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29325299/-hepatitis-c-related-hepatocellular-carcinoma-and-the-treatment-with-direct-acting-antiviral-agents
#8
X Liu, Y H Gao, J Q Niu
With the wide use of direct-acting antiviral agents (DAAs), more and more patients with chronic hepatitis C achieve sustained virological response; however, no consensus has been reached on the application of DAAs in the treatment of hepatitis C virus-related hepatocellular carcinoma (HCC). This article summarizes and evaluates related issues in this field, including whether antiviral therapy with DAAs in patients with hepatitis C can increase the incidence or recurrence rate of HCC, as well as whether DAAs can be used for hepatitis C in HCC patients after antitumor treatment and the efficacy of DAAs in such patients...
December 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/29323755/direct-acting-antiviral-regimens-are-safe-and-effective-in-the-treatment-of-hepatitis-c-in-simultaneous-liver-kidney-transplant-recipients
#9
Anupama U Nookala, James Crismale, Thomas Schiano, Helen Te, Joseph Ahn, Suzanne Robertazzi, Colleen Rodigas, Rohit Satoskar, Mandip Kc, Mohamed Hassan, Coleman Smith
Hepatitis C (HCV) remains the single most common etiology of end-stage liver disease leading to simultaneous liver/kidney transplant (SLKT) and has worse post transplant survival compared to non-HCV patients. We aim to assess the effectiveness and tolerance of the all-oral direct acting antiviral (DAA) agents with or without ribavirin (RBV) in the treatment of HCV recurrence post SLKT. 34 patients were studied retrospectively, composed predominantly of treatment-naïve (73.5%) non-Caucasian (61.8%) males (82...
January 11, 2018: Clinical Transplantation
https://www.readbyqxmd.com/read/29321441/diabetes-mellitus-prevents-an-improvement-in-the-serum-albumin-level-during-interferon-free-sofosbuvir-based-therapy-for-chronic-hepatitis-c-patients-a-multi-institutional-joint-study
#10
Akira Kawano, Hirohisa Shigematsu, Koichiro Miki, Yasunori Ichiki, Chie Morita, Kimihiko Yanagita, Kazuhiro Takahashi, Kazufumi Dohmen, Hideyuki Nomura, Hiromi Ishibashi, Shinji Shimoda
Objective Interferon-free regimens of direct-acting antiviral agents have improved the treatment response for chronic hepatitis C virus (HCV) infection, and improvement in the serum albumin level during interferon-free therapy has been reported. The aim of this study was to identify the factors that influence the improvement in the serum albumin level in patients receiving interferon-free antiviral therapy. Methods This retrospective, multicenter study consisted of 471 Japanese patients with chronic hepatitis and compensated liver cirrhosis infected with HCV who completed 12-week interferon-free sofosbuvir (SOF)-based therapy (SOF plus ledipasvir for genotype 1 [n=276] and SOF with ribavirin for genotype 2 [n=195])...
January 11, 2018: Internal Medicine
https://www.readbyqxmd.com/read/29314670/eliminating-hepatitis-c-virus-as-a-public-health-threat-among-hiv-positive-men-who-have-sex-with-men-a-multi-modelling-approach-to-understand-differences-in-sexual-risk-behaviour
#11
Nick Scott, Mark Stoové, David P Wilson, Olivia Keiser, Carol El-Hayek, Joseph Doyle, Margaret Hellard
INTRODUCTION: Outbreaks of hepatitis C virus (HCV) infections among HIV-positive men who have sex with men (MSM) have been observed globally. Using a multi-modelling approach we estimate the time and number of direct-acting antiviral treatment courses required to achieve an 80% reduction in HCV prevalence among HIV-positive MSM in the state of Victoria, Australia. METHODS: Three models of HCV transmission, testing and treatment among MSM were compared: a dynamic compartmental model; an agent-based model (ABM) parametrized to local surveillance and behavioural data ("ABM1"); and an ABM with a more heterogeneous population ("ABM2") to determine the influence of extreme variations in sexual risk behaviour...
January 2018: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/29290649/retreatment-of-patients-with-treatment-failure-of-direct-acting-antivirals-focus-on-hepatitis-c-virus-genotype-1b
#12
REVIEW
Tatsuo Kanda, Kazushige Nirei, Naoki Matsumoto, Teruhisa Higuchi, Hitomi Nakamura, Hiroaki Yamagami, Shunichi Matsuoka, Mitsuhiko Moriyama
The recent development of direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) infection could lead to higher sustained virological response (SVR) rates, with shorter treatment durations and fewer adverse events compared with regimens that include interferon. However, a relatively small proportion of patients cannot achieve SVR in the first treatment, including DAAs with or without peginterferon and/or ribavirin. Although retreatment with a combination of DAAs should be conducted for these patients, it is more difficult to achieve SVR when retreating these patients because of resistance-associated substitutions (RASs) or treatment-emergent substitutions...
December 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29283325/emerging-trends-in-non-interferon-based-genotype-specific-antiviral-agents-pharmaceutical-perspectives
#13
Tahir Farooq, Arruje Hameed, Kanwal Rehman, Muhammad Ibrahim, Matloob Ahmed, Tahsin Gulzar, Muhammad Sajid Hamid Akash
Hepatitis C virus (HCV) presents a serious global health threat. Initially, the health-care community mainly focused on interferon (IFN)-based therapeutic options to eradicate HCV, but with the passage of time, these applications became unsuitable due to some serious side effects related to the use of IFN. In recent years, research conducted on different phases of HCV's life cycle has opened a new gateway for the use of a direct-acting new generation of anti-HCV agents. Their safer and ultrarapid response has made possible the introduction of triple therapy and use of IFN-free therapeutic treatment strategies...
2017: Critical Reviews in Eukaryotic Gene Expression
https://www.readbyqxmd.com/read/29279506/severe-steroid-responsive-skin-disorders-related-to-ledipasvir-and-sofosbuvir-for-hcv
#14
Tomoko Tadokoro, Asahiro Morishita, Koji Fujita, Kyoko Oura, Teppei Sakamoto, Takako Nomura, Joji Tani, Hirohito Yoneyama, Tsutomu Masaki
Combination therapy with ledipasvir and sofosbuvir (LDV/SOF), direct-acting antiviral agents, is highly effective against hepatitis C virus genotype 1 infection. Although LDV/SOF is safer than conventional treatment, reports have indicated that LDV/SOF was discontinued in certain cases due to severe skin disorders. A 68-year-old woman presented with a rash after starting LDV/SOF treatment. We interrupted LDV/SOF and began the oral administration of prednisolone (PSL). After the rash improved, we re-started LDV/SOF with PSL...
December 27, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29279486/differences-in-the-serum-4%C3%AE-hydroxycholesterol-levels-of-patients-with-chronic-hcv-infection-a-possible-impact-on-the-efficacy-and-safety-of-ifn-free-treatment
#15
Takeshi Hirayama, Tadashi Ikegami, Akira Honda, Teruo Miyazaki, Sho-Ichiro Yara, Motoyuki Kohjima, Makoto Nakamuta, Yasushi Matsuzaki
Since the majority of direct-acting antivirals (DAAs) that are used in the treatment of HCV infection are mainly metabolized by CYP3A4, it is hypothesized that inter-individual differences in CYP3A4 activity may be associated with the bioavailability of these agents. Methods The level of serum 4β-hydroxycholesterol (4βHC), a surrogate marker of CYP3A4 activity, was determined by LC-MS/MS in samples obtained from patients with HCV infection (CHCs) as well as healthy control subjects (CTLs). Serum samples obtained from patients treated with either asunaprevir/daclatasvir (ASV/DCV) or ombitasvir/paritaprevir/ritonavir (OTV/PTV/r) were used for additional assays...
December 27, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29276983/uplc-ms-ms-method-for-the-simultaneous-quantification-of-sofosbuvir-sofosbuvir-metabolite-gs-331007-and-daclatasvir-in-plasma-of-hiv-hcv-co-infected-patients
#16
Stefania Notari, Massimo Tempestilli, Gabriele Fabbri, Raffaella Libertone, Andrea Antinori, Adriana Ammassari, Chiara Agrati
Direct-acting antiviral agents (DAAs) represent the major advance in hepatitis C virus (HCV) infection treatment leading to extremely high eradication rates in HCV mono- and HIV/HCV co-infected patients. In this scenery, availability of Therapeutic Drug Monitoring (TDM) is of interest to assess plasma concentrations to prevent either therapeutic failure due to suboptimal medication adherence and drug-drug interactions or avoid adverse events. Aim of this study was to develop and validate an Ultra-Performance Liquid Chromatography Mass Spectrometry (UPLC-MS/MS) method for the simultaneous quantification of sofosbuvir, sofosbuvir metabolite (GS-331007), and daclatasvir in human plasma...
December 12, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29274192/uptake-of-direct-acting-antiviral-treatment-for-chronic-hepatitis-c-in-australia
#17
Behzad Hajarizadeh, Jason Grebely, Gail V Matthews, Marianne Martinello, Gregory J Dore
A Government-funded interferon-free direct acting antiviral (DAA) treatment program for chronic hepatitis C virus (HCV) infection has been available in Australia since March 2016. This study assessed the levels and patterns of DAA treatment uptake during March-December 2016 in Australia, and described the key features in development of the program. All prescriptions in Australia are submitted to the Pharmaceutical Benefits Scheme by dispensing pharmacies. Data on dispensed DAA prescriptions for a longitudinal cohort of individuals, representing a 10% random sample of the Pharmaceutical Benefits Scheme database, were used for estimating DAA treatment uptake and sub-group analyses...
December 23, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29247725/toll-like-receptor-7-agonist-gs-9620-induces-prolonged-inhibition-of-hbv-via-a-type-i-interferon-dependent-mechanism
#18
Congrong Niu, Li Li, Stephane Daffis, Julie Lucifora, Marc Bonnin, Sarah Maadadi, Eduardo Salas, Ruth Chu, Hilario Ramos, Christine M Livingston, Rudolf K Beran, Abhishek V Garg, Scott Balsitis, David Durantel, Fabien Zoulim, William E Delaney, Simon P Fletcher
BACKGROUND & AIMS: GS-9620, an oral agonist of toll-like receptor 7 (TLR7), is in clinical development for the treatment of chronic hepatitis B (CHB). GS-9620 was previously shown to induce prolonged suppression of serum viral DNA and antigens in the woodchuck and chimpanzee models of CHB. Here we investigated the molecular mechanisms that contribute to the antiviral response to GS-9620 using in vitro models of hepatitis B virus (HBV) infection. METHODS: Cryopreserved primary human hepatocytes (PHH) and differentiated HepaRG (dHepaRG) cells were infected with HBV and treated with GS-9620, conditioned media from human peripheral blood mononuclear cells (PBMCs) treated with GS-9620 (GS-9620 conditioned media; GS-9620-CM), or other innate immune stimuli...
December 13, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/29246310/inhibition-of-murine-cytomegalovirus-infection-in-animals-by-rnase-p-associated-external-guide-sequences
#19
Wei Li, Jingxue Sheng, Mengqiong Xu, Gia-Phong Vu, Zhu Yang, Yujun Liu, Xu Sun, Phong Trang, Sangwei Lu, Fenyong Liu
External guide sequence (EGS) RNAs are associated with ribonuclease P (RNase P), a tRNA processing enzyme, and represent promising agents for gene-targeting applications as they can direct RNase-P-mediated cleavage of a target mRNA. Using murine cytomegalovirus (MCMV) as a model system, we examined the antiviral effects of an EGS variant, which was engineered using in vitro selection procedures. EGSs were used to target the shared mRNA region of MCMV capsid scaffolding protein (mCSP) and assemblin. In vitro, the EGS variant was 60 times more active in directing RNase P cleavage of the target mRNA than the EGS originating from a natural tRNA...
December 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/29242710/retreatment-options-following-hcv-direct-acting-antiviral-failure
#20
Autumn Zuckerman, Cody A Chastain, Susanna Naggie
Despite the excellent efficacy of direct acting antivirals (DAA) for hepatitis C virus (HCV), treatment failures do occur. Until recently, retreatment decisions after DAA failure were influenced by the number of available agents, concerns about HCV drug resistance, and lack of data regarding retreatment. Recommended treatment approaches previously depended on limited clinical trials and expert opinion. In this article, we review the current state of the evidence for HCV retreatment after DAA failure. Based on recent clinical trial data, most patients who fail HCV treatment with DAA agents now have excellent retreatment options...
December 2017: Current Treatment Options in Infectious Diseases
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