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Jacob Lauwring Andersen, Borbala Gesser, Erik Daa Funder, Christine Juul Fælled Nielsen, Helle Gotfred-Rasmussen, Mads Kirchheiner Rasmussen, Rachel Toth, Kurt Vesterager Gothelf, J Simon C Arthur, Lars Iversen, Poul Nissen
Dimethyl fumarate (DMF) has been applied for decades in the treatment of psoriasis and now also multiple sclerosis. However, the mechanism of action has remained obscure and involves high dose over long time of this small, reactive compound implicating many potential targets. Based on a 1.9 Å resolution crystal structure of the C-terminal kinase domain of the mouse p90 Ribosomal S6 Kinase 2 (RSK2) inhibited by DMF we describe a central binding site in RSKs and the closely related Mitogen and Stress-activated Kinases (MSKs)...
October 19, 2018: Nature Communications
Arash Vaziri, Alexander Gimson, Kosh Agarwal, Mark Aldersley, Andrew Bathgate, Douglas MacDonald, Stuart McPherson, David Mutimer, William Gelson
Following the introduction of direct acting antivirals (DAA), there have been reports of declining incidence of hepatitis C (HCV) related liver disease as a liver transplantation indication. In this study we assessed the impact of DAA on liver transplant indications in the UK and waiting list outcomes for patients with HCV. We assessed UK adult elective liver transplant registrants between 2006 and 2017. The aetiology of liver disease at registration was reclassified using an accepted hierarchical system and changes were assessed over time and compared before and after the introduction of DAA...
October 19, 2018: Journal of Viral Hepatitis
Jack Wallace, Bev Hanley, Mary Belfrage, Sandra Gregson, Niall Quiery, Jayne Lucke
Aboriginal and Torres Strait Islander peoples are disproportionately affected by hepatitis C, an infection that is curable with direct acting antivirals (DAAs). The Australian Government funded access to DAAs from March 2016 for all people with hepatitis C, with primary care physicians, along with clinical specialists, permitted to prescribe these treatments. The Victorian Aboriginal Health Service, in recognising the effect of liver disease from viral hepatitis within their community, and of the increased availability to DAAs, established a Liver Clinic to facilitate access to treatment for people attending the service...
October 19, 2018: Australian Journal of Primary Health
Mizuki Nishibatake Kinoshita, Tatsuya Minami, Ryosuke Tateishi, Taijiro Wake, Ryo Nakagomi, Naoto Fujiwara, Masaya Sato, Koji Uchino, Kenichiro Enooku, Hayato Nakagawa, Yoshinari Asaoka, Shuichiro Shiina, Kazuhiko Koike
BACKGROUND AND AIMS: It remains controversial whether direct-acting antivirals (DAA) accelerate the recurrence of hepatitis C-related hepatocellular carcinoma (HCC) after curative therapy. This study aimed to evaluate HCC recurrence after DAA treatment of chronic hepatitis C. METHODS: We enrolled patients with a history of successful radiofrequency ablation treatment for hepatitis C-related HCC who received antiviral therapy with DAA (DAA group: 147 patients) or with interferon (IFN)-based therapy (IFN group: 156 patients)...
October 15, 2018: Journal of Hepatology
Takao Watanabe, Yoshio Tokumoto, Kouji Joko, Kojiro Michitaka, Norio Horiike, Yoshinori Tanaka, Fujimasa Tada, Yoshiyasu Kisaka, Seiji Nakanishi, Kazuhiko Yamauchi, Atsushi Yukimoto, Masashi Hirooka, Masanori Abe, Yoichi Hiasa
AIM: The predictors for the development of hepatocellular carcinoma (HCC) after direct-acting antiviral (DAA) treatment were investigated. METHODS: A total of 1174 patients with chronic HCV infection were treated with DAA therapy (sofosbuvir and ledipasvir [n=615], sofosbuvir and ribavirin [n=380], and daclatasvir and asunaprevir [n=179]) and achieved sustained virological response (SVR). The HCC development rate and the factors that might contribute to the development of HCC after the end of DAA treatment were analyzed...
October 18, 2018: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Mitsutaka Osawa, Michio Imamura, Yuji Teraoka, Takuro Uchida, Kei Morio, Hatsue Fujino, Takashi Nakahara, Atsushi Ono, Eisuke Murakami, Tomokazu Kawaoka, Daiki Miki, Masataka Tsuge, Akira Hiramatsu, Hiroshi Aikata, C Nelson Hayes, Kazuaki Chayama
BACKGROUND: Combination therapy with glecaprevir (GLE) and pibrentasvir (PIB) has high efficacy for pan-genotypic hepatitis C virus (HCV)-infected patients. However, the efficacy of the therapy for failures to prior direct-acting antiviral (DAA) regimens in real-world practice is not well known. METHODS: Thirty patients infected with HCV genotype 1b, 2a, 2b, or 3a who failed to respond during prior DAA therapies were treated with GLE/PIB for 12 weeks. HCV NS3 and NS5A drug resistance-associated variants (RAVs) were determined by direct sequencing...
October 17, 2018: Journal of Gastroenterology
Andrea Casadei Gardini, Francesco Giuseppe Foschi, Fabio Conti, Elisabetta Petracci, Ranka Vukotic, Giorgia Marisi, Federica Buonfiglioli, Giovanni Vitale, Federico Ravaioli, Stefano Gitto, Gabriella Verucchi, Marco Lenzi, Luigi Bolondi, Giuseppe Mazzella, Stefano Brillanti, Pietro Andreone
BACKGROUND: Unexpectedly high occurrence or recurrence rate of hepatocellular carcinoma (HCC) has been observed in patients with chronic hepatitis C receiving direct-acting antivirals (DAAs) therapy. AIMS: We evaluated the predictive value of albumin-bilirubin (ALBI) score and immune-inflammation indicators to identify the risk of occurrence or recurrence of HCC in patients treated with DAAs in a real life setting. METHODS: In this retrospective cohort study, we analysed data from 514 patients with cirrhosis who were prospectively enrolled for treatment with DAAs...
September 22, 2018: Digestive and Liver Disease
Lele Zhou, Qi Kang, Oiongzheng Hu, Li Yu
Glutathione (GSH) is of significance in human pathology due to its many cellular functions. γ-Glutamyl transpeptidase (γ-GT) plays a key role in the balance of GSH by breaking down extracellular GSH. In this study, we proposed a novel strategy for sensitive and selective detection of GSH based on LC sensing platform coupled with its inhibition of γ-GT. The γ-GT cleavable surfactant, dodecyl N-ethanamide N, N, N-trimethylammonium bromide (DAA), was synthesized and utilized to decorate the aqueous/LC interface...
December 21, 2018: Analytica Chimica Acta
Maria Mazzitelli, Carlo Torti, Jolanda Sabatino, Greta Luana D'Ascoli, Chiara Costa, Vincenzo Pisani, Elena Raffetti, Salvatore De Rosa, Alessio Strazzulla, Alfredo Focà, Maria Carla Liberto, Ciro Indolfi
BACKGROUND: Possible cardiotoxicity of sofosbuvir in humans has not been demonstrated yet. Also, since HCV can exert deleterious effects on hearth function, it is of interest to know whether HCV eradication provides any benefits using global longitudinal strain (GLS), a measure of left ventricular function more reliable than ejection fraction (EF). METHODS: Patients eligible for treatment with the combination therapy for HCV were invited to perform a transthoracic cardiac ultrasound at four different time points: before starting treatment, after one month, at the end of treatment and, after six month...
October 16, 2018: BMC Infectious Diseases
Kathrin Krüger, Christian Krauth, Siegbert Rossol, Stefan Mauss, Klaus H W Boeker, Tobias Müller, Hartwig Klinker, Anita Pathil, Renate Heyne, Jona T Stahmeyer
OBJECTIVE: Chronic hepatitis C virus infection is associated with a significant health burden. Long-term consequences are the development of liver cirrhosis and hepatocellular carcinoma. The introduction of direct-acting antivirals (DAA) has led to an increase in sustained virologic response rates (SVR), but is accompanied by higher treatment costs. The aim of this study was to assess the outcomes and costs of treating hepatitis C virus infected patients with DAAs in clinical practice in Germany...
October 15, 2018: European Journal of Gastroenterology & Hepatology
Jens Jap, Ian J Saldanha, Bryant T Smith, Joseph Lau, Christopher H Schmid, Tianjing Li
INTRODUCTION: During systematic reviews, data abstraction is labor- and time-intensive and error-prone. Existing data abstraction systems do not track specific locations and contexts of abstracted information. To address this limitation, we developed a software application, the Data Abstraction Assistant (DAA), and surveyed early users about their experience using DAA. FEATURES OF DAA: We designed DAA to encompass three essential features: (1) a platform for indicating the source of abstracted information; (2) compatibility with a variety of data abstraction systems; and (3) user-friendliness...
October 16, 2018: Research Synthesis Methods
Adel Abdel-Moneim, Alaa Abood, Mohamed Abdel-Gabaar, Mohamed I Zanaty, Mohamed Ramadan
Introduction: New regimens involving direct-acting antiviral agents (DAAs) have recently been approved for the treatment of hepatitis C virus (HCV) genotype 4 (GT4). The current study aims to assess the efficacy and safety of sofosbuvir (SOF) with pegylated interferon (PegINF)/ribavirin (RBV) for chronic HCV GT4 patients at the beginning of the interferon-free era. Material and methods: Between March 2015 and November 2015, 99 patients (59 naïve and 40 experienced) infected with HCV GT4 were enrolled in the study...
September 2018: Clinical and Experimental Hepatology
Mohamed A Ibrahim, Asmaa Abdel-Aziz, Azza El-Sheikh, Maha Kamel, Al-Zahraa Khalil, Hisham Abdelhaleem
Introduction: The study aimed at investigating the hepatic effect of direct acting anti-hepatitis C virus drugs (DAAs), sofosbuvir (Sof) and daclatasvir (Dac), in thioacetamide (TAA)-induced liver injury in rats. Material and methods: Animals were allocated to 7 groups: a normal control group, a TAA group (receiving TAA 50 mg/kg, i.p. twice weekly), two TAA groups receiving either a low or a high dose of Sof (Sof-L and Sof-H; 41.1 mg/kg and 82.2 mg/kg, respectively), two TAA groups receiving either a low or a high dose of Dac (Dac-L and Dac-H; 6...
September 2018: Clinical and Experimental Hepatology
Juan Marín-Lahoz, Javier Pagonabarraga, Saul Martinez-Horta, Ramón Fernandez de Bobadilla, Berta Pascual-Sedano, Jesús Pérez-Pérez, Alexandre Gironell, Jaime Kulisevsky
Introduction: Impulse control disorders (ICDs) are a common complication of Parkinson's disease (PD) receiving dopamine agonist (DAA) Impulsivity is considered an underlying mechanism but evidence of this relationship is scarce. To explore the relationship between impulsivity and the presence and severity of ICD in PD. Methods: Prospective cross-sectional study of consecutive PD outpatients. Patients with dementia or previously known ICDs were excluded. Two measures of impulsivity were assessed: Barratt Impulsiveness Scale (BIS-11) for impulsiveness trait (main exposure) and commission errors in the Continuous Performance Test (CE) for motor inhibition...
2018: Frontiers in Psychiatry
Anne C Spaulding, Jagpreet Chhatwal, Madeline G Adee, Robert T Lawrence, Curt G Beckwith, William von Oehsen
The cost of treating all incarcerated people who have hepatitis C with direct-acting antiviral agents (DAAs) greatly stresses correctional facility budgets. Complex federal laws bar pharmaceutical companies from simply discounting expensive medications to prices that facilities can afford. This article discusses means by which correctional facilities may qualify under federal law as "safety-net providers" to allow sale of DAAs at a price <10% of the average manufacturer price (AMP). No new laws would need to be enacted to implement this strategy...
October 15, 2018: Journal of Correctional Health Care
Alexander Breskin, Daniel Westreich, Stephen R Cole, Michael G Hudgens, Christopher B Hurt, Eric C Seaberg, Chloe L Thio, Phyllis C Tien, Adaora A Adimora
Background: Persons living with human immunodeficiency virus (HIV; PLwH) are commonly co-infected with hepatitis C virus (HCV). Most co-infected individuals can achieve a sustained HCV virologic response after treatment with direct-acting antivirals (DAA). However, the effect of HCV co-infection and DAA treatment on mortality after initiating antiretroviral therapy (ART) is unknown for PLwH. Methods: We analyzed data from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study...
October 12, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Saikat Banerjee, Sampada Kumar Dash
Research on effectiveness of DAA is limited. Existing researches explore impact of DAA only on relationship between drug manufacturers and consumers. However, in reality, pharma marketing revolves around three major stakeholders: the pharmaceutical companies, physicians and consumers. Pharmaceutical professionals on behalf of drug manufacturers have last mile connectivity with end users and they are an important stakeholder in this entire marketing relationship network. So, it is important for marketers to capture views of pharma professionals in addition to physicians and consumers...
October 15, 2018: Health Marketing Quarterly
Dario Akaberi, Assar Bergfors, Midori Kjellin, Nader Kameli, Louise Lidemalm, Bhavya Kolli, Robert W Shafer, Navaneethan Palanisamy, Johan Lennerstrand
Background: Current combination treatments with direct-acting antiviral agents (DAAs) can cure more than 95% of hepatitis C virus (HCV) infections. However, resistance-associated substitutions (RASs) may emerge and can also be present in treatment-naïve patients. Methods, results and discussion: In this study, a semi-pan-genotypic population sequencing method was developed and used to assess all NS5B amino acid variants between residue positions 310 and 564. Our method successfully sequenced more than 90% of genotype (GT) 1a, 1b, 2b and 3a samples...
2018: Infection Ecology & Epidemiology
(no author information available yet)
Approved direct-acting antiviral agents (DAA ) in chronic hepatitis C were introduced. Metabolism and pharmacokinetics data of DAAs were analyzed. Comorbidity and concomitant medications of chronic hepatitis C (CHC) patients were extracted from Chinese Health Insurance database. Drug-drug interactions (DDIs) were calculated by integrated above data and confirmed by using Liverpool DDI website. Based on those data, experts propose consensus on management of drug-drug interaction with direct-acting antiviral agents in chronic hepatitis C, including pre-treatment, on-treatment, and post-treatment...
July 20, 2018: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Chun-Ming Hong, Chen-Hua Liu, Tung-Hung Su, Hung-Chih Yang, Pei-Jer Chen, Yu-Wen Chen, Jia-Horng Kao, Chun-Jen Liu
BACKGROUND/PURPOSE: Treatment of chronic hepatitis C (CHC) has entered a new era since the introduction of direct-acting antiviral agents (DAAs). Numerous clinical trials have shown that treatment response as well as tolerability of DAAs are superior to those of conventional therapy with pegylated interferon and ribavirin. However, the results of clinical trials may not be directly applied to real-world practice. Therefore our study tried to investigate the effectiveness of various DAA regimens in Taiwanese patients with chronic hepatitis C...
September 26, 2018: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
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