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https://www.readbyqxmd.com/read/28804573/changing-landscape-of-hepatitis-c-virus-positive-donors
#1
Catherine E Kling, Ajit P Limaye, Lena Sibulesky
With the introduction of the new highly effective antiviral therapies, there has been a dramatic increase in the use of the hepatitis C virus (HCV)-positive livers in HCV-positive recipients. In the majority of studies, HCV positivity was defined as a donor testing HCV Ab positive. In 2015, all Organ Procurement Organizations were mandated to perform and report HCV Nucleic Acid Amplification Testing (NAT) results on all deceased and living donors. Studies are not yet available on how organs are being utilized based on NAT status and whether NAT status affects recipient outcomes...
July 18, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28802816/safety-and-efficacy-of-an-8-week-regimen-of-grazoprevir-plus-ruzasvir-plus-uprifosbuvir-compared-with-grazoprevir-plus-elbasvir-plus-uprifosbuvir-in-participants-without-cirrhosis-infected-with-hepatitis-c-virus-genotypes-1-2-or-3-c-crest-1-and-c-crest-2-part
#2
Edward J Gane, Stephen Pianko, Stuart K Roberts, Alexander J Thompson, Stefan Zeuzem, Eli Zuckerman, Ziv Ben-Ari, Graham R Foster, Kosh Agarwal, Alex L Laursen, Jan Gerstoft, Wei Gao, Hsueh-Cheng Huang, Brian Fitzgerald, Doreen Fernsler, Jerry J Li, Anjana Grandhi, Hong Liu, Feng-Hsiu Su, Shuyan Wan, Zhen Zeng, Huei-Ling Chen, Frank J Dutko, Bach-Yen T Nguyen, Janice Wahl, Michael N Robertson, Eliav Barr, Wendy W Yeh, Rebeca M Plank, Joan R Butterton, Rafael Esteban
BACKGROUND: New hepatitis C virus (HCV) therapies with pan-genotypic efficacy are needed. The goals of part A of C-CREST-1 and C-CREST-2 were to compare the efficacies of two doses (300 mg or 450 mg once daily) of uprifosbuvir (MK-3682; NS5B inhibitor) in an 8-week regimen combined with grazoprevir (NS3/4A inhibitor; 100 mg once daily) and an NS5A inhibitor, either elbasvir (50 mg once daily) or ruzasvir (MK-8408; 60 mg once daily), and to evaluate the safety and tolerability of these combination regimens in individuals infected with genotypes 1, 2, or 3...
August 9, 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28802815/shortening-the-duration-of-therapy-for-chronic-hepatitis-c-infection
#3
REVIEW
Benjamin Emmanuel, Eleanor M Wilson, Thomas R O'Brien, Shyam Kottilil, George Lau
Combination direct-acting antiviral therapy of 8-24 weeks is highly effective for the treatment of chronic hepatitis C infection. However, shortening the treatment duration to less than 8 weeks could potentially reduce overall treatment costs and improve adherence. Here we explore the arguments for and against the development of short-duration regimens and existing data on treatment for 6 weeks or less among patients with chronic hepatitis C virus genotype 1 infection. Additionally, we identify potential predictors of response to short-course combination therapies with direct-acting antiviral drugs that might be explored in future clinical trials...
August 9, 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28802814/safety-and-efficacy-of-a-fixed-dose-combination-regimen-of-grazoprevir-ruzasvir-and-uprifosbuvir-with-or-without-ribavirin-in-participants-with-and-without-cirrhosis-with-chronic-hepatitis-c-virus-genotype-1-2-or-3-infection-c-crest-1-and-c-crest-2-part-b-two
#4
Eric Lawitz, Maria Buti, John M Vierling, Piero L Almasio, Savino Bruno, Peter J Ruane, Tarek I Hassanein, Beat Muellhaupt, Brian Pearlman, Ligita Jancoriene, Wei Gao, Hsueh-Cheng Huang, Aimee Shepherd, Brynne Tannenbaum, Doreen Fernsler, Jerry J Li, Anjana Grandhi, Hong Liu, Feng-Hsiu Su, Shuyan Wan, Frank J Dutko, Bach-Yen T Nguyen, Janice Wahl, Michael N Robertson, Eliav Barr, Wendy W Yeh, Rebeca M Plank, Joan R Butterton, Eric M Yoshida
BACKGROUND: There is a need for hepatitis C virus (HCV) therapies with excellent efficacy across genotypes and in diverse populations. Part A of the C-CREST-1 and C-CREST-2 trials led to the selection of a three-drug regimen of grazoprevir (MK-5172; an HCV NS3/4A protease inhibitor; 100 mg/day) plus ruzasvir (MK-8408; an NS5A inhibitor; 60 mg/day) plus uprifosbuvir (MK-3682; an HCV NS5B polymerase inhibitor; 450 mg/day). Part B of the studies tested this combination as a single formulation in different treatment durations in a broader population...
August 9, 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28801074/rational-heart-transplant-from-hepatitis-c-donor-new-antiviral-weapons-conquer-the-trojan
#5
Robert L Gottlieb, Teena Sam, Suzanne Y Wada, James F Trotter, Sumeet K Asrani, Brian Lima, Susan M Joseph, Gonzalo Gonzalez-Stawinski, Shelley A Hall
BACKGROUND: Donors with hepatitis C (HCV) viremia are rarely utilized for orthotopic heart transplantation (OHTx) due to post-transplant risks. New, highly effective HCV antivirals may alter the landscape. METHODS: An adult patient unsuitable for bridging mechanical support therapy accepted a heart transplant offer from a donor with HCV viremia. Upon daily logarithmic rise in HCV viral load and adequate titers to ensure successful genotyping, once daily sofosbuvir 400 mg / velpatasvir 100 mg (Epclusa) was initiated empirically pending HCV genotype (genotype 3a confirmed after initiation of therapy)...
August 8, 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/28800195/pharmacokinetics-safety-and-tolerability-of-glecaprevir-and-pibrentasvir-in-healthy-white-chinese-and-japanese-adult-subjects
#6
Chih-Wei Lin, Sandeep Dutta, Bifeng Ding, Tianli Wang, Neddie Zadeikis, Armen Asatryan, Jens Kort, Andrew Campbell, Thomas Podsadecki, Wei Liu
Glecaprevir and pibrentasvir are direct-acting antiviral agents being developed as combination therapy for the treatment of chronic hepatitis C virus infection. The aim of the present studies was to assess the effect of race and ethnicity (white, Han Chinese, Japanese) on the pharmacokinetics and safety of multiple oral doses of glecaprevir and pibrentasvir given alone and in combination. Two multiple-dose, single-center, phase 1 studies were conducted in healthy adult male and female subjects (n = 170) of respective Asian and white race/ethnicity...
August 11, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28800033/predictors-of-early-discontinuation-of-interferon-free-direct-antiviral-agents-in-patients-with-hepatitis-c-virus-and-advanced-liver-fibrosis-results-of-a-real-life-cohort
#7
Noelle Miotto, Leandro C Mendes, Letícia P Zanaga, Eduardo S L Goncales, Maria S K Lazarini, Marcelo N Pedro, Fernando L Gonçales, Raquel S B Stucchi, Aline G Vigani
AIM: The aim of this study was to determine risk factors for premature treatment discontinuation among patients with hepatitis C and advanced fibrosis with advanced fibrosis treated with interferon (IFN)-free direct antiviral agents (DAA)-based therapy. PATIENTS AND METHODS: We included all patients with chronic hepatitis C virus infection and advanced liver fibrosis in whom treatment was initiated with IFN-free DAA therapy at a university hospital from December 2015 through June 2016...
August 10, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28799277/the-italian-compassionate-use-of-sofosbuvir-itacops-observational-cohort-study-for-the-treatment-of-recurrent-hepatitis-c-clinical-and-virological-outcomes
#8
Paola Carrai, Cristina Morelli, Gabriella Cordone, Antonietta Romano, Mariarosa Tamé, Raffaella Lionetti, Giada Pietrosi, Ilaria Lenci, Guido Piai, Francesco Paolo Russo, Carmine Coppola, Mario Melazzini, Simona Montilla, Luca Pani, Sandra Petraglia, Pierluigi Russo, Maria Paola Trotta, Silvia Martini, Pierluigi Toniutto
Direct antivirals are available for treating recurrent hepatitis C (RHC). This study reported outcomes of 424 patients with METAVIR F3-F4 RHC who were treated for 24 weeks with sofosbuvir/ribavirin and followed for 12 weeks within the Italian sofosbuvir compassionate use program. In 55 patients, daclatasvir or simeprevir were added. Child-Pugh class and MELD scores were evaluated at baseline and 36 weeks after the start of therapy. The sustained viral response (SVR) was 86.7% (316/365) in patients who received sofosbuvir/ribavirin and 98...
August 11, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28798283/healthcare-costs-for-chronic-hepatitis-c-in-south-korea-from-2009-to-2013-an-analysis-of-the-national-health-insurance-claims-data
#9
Moran Ki, Hwa Young Choi, Kyung-Ah Kim, Eun Sun Jang, Sook-Hyang Jeong
Background/Aims: The introduction of direct-acting antivirals (DAA) in 2013 revolutionized hepatitis C virus (HCV) treatment, offering a cure rate >90%. However, this therapy is expensive, and estimations of the number of chronic HCV-infected (CHC) patients and their treatment costs pre-2013 are therefore essential for creating policies and expanding drug access. Herein, we aimed to investigate the number of HCV-related liver disease patients, their healthcare utilization, their annual direct medical costs, and the interferon-based antiviral treatment rates and costs from 2009 to 2013 in South Korea...
August 14, 2017: Gut and Liver
https://www.readbyqxmd.com/read/28797532/assessment-of-in-vitro-antifungal-efficacy-and-in-vivo-toxicity-of-amphotericin-b-loaded-plga-and-plga-peg-blend-nanoparticles
#10
T C Moraes Moreira Carraro, C Altmeyer, N Maissar Khalil, R Mara Mainardes
Amphotericin B (AmB) is widely applied in treatment of systemic fungal infections. However, the emergence of severe adverse effects, such as nephrotoxicity, hepatotoxicity and hemolytic anemia, can limit its clinical use. Poly(lactide-co-glycolide) (PLGA) or poly(lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) blend nanoparticles containing AmB were developed with the aim to decrease AmB toxicity and propose the oral route for AmB delivery. Nanoparticles were characterized by particle size, polydispersity index, Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffraction analyses...
August 7, 2017: Journal de Mycologie Médicale
https://www.readbyqxmd.com/read/28797497/reaching-hepatitis-c-virus-elimination-targets-requires-health-system-interventions-to-enhance-the-care-cascade
#11
Nick Scott, Joseph S Doyle, David P Wilson, Amanda Wade, Jess Howell, Alisa Pedrana, Alexander Thompson, Margaret E Hellard
BACKGROUND: Modelling suggests that achieving the World Health Organization's elimination targets for hepatitis C virus (HCV) is possible by scaling up use of direct-acting antiviral (DAA) therapy. However, poor linkage to health services and retention in care presents a major barrier, in particular among people who inject drugs (PWID). We identify and assess the cost-effectiveness of additional health system interventions required to achieve HCV elimination targets in Australia, a setting where all people living with HCV have access to DAA therapy...
August 7, 2017: International Journal on Drug Policy
https://www.readbyqxmd.com/read/28797159/clinical-implication-of-serum-uric-acid-level-in-pegylated-interferon-and-ribavirin-combination-therapy-for-chronic-hepatitis-c-infection
#12
In Soo Oh, Joung Won Won, Hyung Joon Kim, Hyun Woong Lee
Background/Aims: Combined treatment of pegylated interferon-α (PEG-IFN) and ribavirin (RBV) has long been accepted as the standard treatment for chronic hepatitis C virus (HCV) infection. Many predictive factors for treatment response have been identified. The aim of this study was to evaluate the efficacy and safety of combined PEG-IFN plus RBV and to examine the value of serum uric acid as a predictive factor in the treatment of chronic hepatitis C. Methods: A total of 74 patients chronically infected with HCV were enrolled between December 2004 and June 2009...
August 11, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28797106/the-risks-of-hepatocellular-carcinoma-development-after-hcv-eradication-are-similar-between-patients-treated-with-peg-interferon-plus-ribavirin-and-direct-acting-antiviral-therapy
#13
Yuko Nagaoki, Michio Imamura, Hiroshi Aikata, Kana Daijo, Yuji Teraoka, Fumi Honda, Yuki Nakamura, Masahiro Hatooka, Reona Morio, Kei Morio, Hiromi Kan, Hatsue Fujino, Tomoki Kobayashi, Keiichi Masaki, Atsushi Ono, Takashi Nakahara, Tomokazu Kawaoka, Masataka Tsuge, Akira Hiramatsu, Yoshiiku Kawakami, C Nelson Hayes, Daiki Miki, Hidenori Ochi, Kazuaki Chayama
The risk of hepatocellular carcinoma (HCC) development is reduced following viral elimination by interferon therapy in chronic hepatitis C patients. However, the risk in patients treated with interferon-free direct-acting antivirals (DAAs) is unknown. We evaluated chronic hepatitis C patients who achieved viral eradication by pegylated-interferon plus ribavirin (PEG-IFN/RBV, n = 244) or daclatasvir plus asunaprevir (DCV/ASV, n = 154) therapy. None of the patients had prior history of HCC or antiviral therapy...
2017: PloS One
https://www.readbyqxmd.com/read/28797039/impact-of-pnpla3-and-ifnl3-polymorphisms-on-hepatic-steatosis-in-asian-patients-with-chronic-hepatitis-c
#14
Chao-Min Huang, Kuo-Chin Chang, Chao-Hung Hung, King-Wah Chiu, Sheng-Nan Lu, Jing-Houng Wang, Chien-Hung Chen, Kwong-Ming Kee, Yuan-Hung Kuo, Ming-Chao Tsai, Po-Lin Tseng, Ming-Tsung Lin, Cheng-Kun Wu, Tsung-Hui Hu, Chung-Lung Cho, Yi-Hao Yen
BACKGROUND AND AIMS: A recent meta-analysis revealed that the genotype PNPLA3 rs738409 GG is associated with a higher risk of hepatic steatosis (HS) in Caucasian patients with chronic hepatitis C (CHC). However, controversial results were found regarding Asian populations. Furthermore, previous studies have shown a negative association between interferon lambda 3 (IFNL3) rs12979860 CC and HS in Caucasian CHC patients, but there have been no reports indicating any such association in Asian populations...
2017: PloS One
https://www.readbyqxmd.com/read/28796673/human-immunodeficiency-virus-viral-load-rebound-near-delivery-in-previously-suppressed-combination-antiretroviral-therapy-treated-pregnant-women
#15
Isabelle Boucoiran, Arianne Y K Albert, Karen Tulloch, Emily C Wagner, Neora Pick, Julie van Schalkwyk, P Richard Harrigan, Deborah Money
OBJECTIVE: To assess the stability of human immunodeficiency virus (HIV) viral load suppression within 1 month before birth in pregnant women receiving antenatal combination antiretroviral therapy (CART). METHODS: This is a retrospective cohort study of a Canadian provincial perinatal HIV database from 1997 to 2015. Inclusion criteria were live birth and CART received for at least 4 weeks. Viral load rebound, defined as viral load greater than 50 copies/mL (or greater than 400 copies/mL for 1997-1998) and measured within 1 month before delivery, was identified in women who had at least one previous undetectable viral load during pregnancy...
August 4, 2017: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28796591/utilization-of-buprenorphine-and-methadone-among-opioid-users-who-inject-drugs
#16
Judith I Tsui, Richard Burt, Hanne Thiede, Sara N Glick
BACKGROUND: There has been a rise in opioid abuse and related injection drug use in the United States and treatment for opioid use disorders may be underutilized. The study aim was to describe utilization of opioid agonist therapy (OAT), and assess factors associated with utilization of OAT, among persons who inject drugs (PWID) in the Seattle metropolitan area. METHODS: We used data from the 2015 National HIV Behavioral Surveillance (NHBS) system among PWID in the Seattle area...
August 10, 2017: Substance Abuse
https://www.readbyqxmd.com/read/28796032/nomogram-for-individualized-prediction-of-recurrence-after-postoperative-adjuvant-tace-for-hepatitis-b-virus-related-hepatocellular-carcinoma
#17
Jiang Jiang, Hao Hu, Rong Liu, Jian Hua Wang, Xiao Ran Long, Jia Fan, Zhi Ping Yan
This study sought to develop an effective and reliable nomogram for predictions of recurrence for postoperative adjuvant transarterial chemoembolization (PA-TACE) in patients with hepatitis B virus-related (HBV) hepatocellular carcinoma (HCC).The nomogram was established based on data obtained from a retrospective study on 235 consecutive patients with HBV HCC who received PA-TACE as an initial therapy from 2006 to 2010 in our center. Eighty-four patients who were collected at another institution between 01/2008 and 12/2010 served as an external validation set...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28795238/efficacy-and-safety-of-sofosbuvir-based-interferon-free-therapy-the-management-of-rheumatologic-extrahepatic-manifestations-associated-with-chronic-hepatitis-c%C3%A2-virus-infection
#18
A A Shahin, H S Zayed, M Said, S A Amer
BACKGROUND: The use of pegylated interferon alpha (IFN) has been of concern in chronic hepatitis C virus (HCV) patients with rheumatologic extrahepatic manifestations (EHM) due to the immunostimulatory effects of IFN. AIM: To study the efficacy and safety of sofosbuvir-based, IFN-free antiviral therapy in chronic HCV patients with rheumatologic EHM. MATERIAL AND METHODS: Group A included 24 patients with arthropathy (arthralgia or arthritis, n = 15) or vasculitis (n = 9) who received sofosbuvir and ribavirin (n = 17) or sofosbuvir and simeprevir (n = 7)...
August 9, 2017: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/28794069/phase-i-study-of-the-anti-cd22-immunotoxin-moxetumomab-pasudotox-for-childhood-acute-lymphoblastic-leukemia
#19
Alan S Wayne, Nirali N Shah, Deepa Bhojwani, Lewis B Silverman, James A Whitlock, Maryalice Stetler-Stevenson, Weili Sun, Meina Liang, Jie Yang, Robert J Kreitman, Mark C Lanasa, Ira Pastan
Novel therapies are needed to overcome chemotherapy resistance for children with relapsed/refractory acute lymphoblastic leukemia (ALL). Moxetumomab pasudotox is a recombinant anti-CD22 immunotoxin. A multicenter, phase I study was conducted to determine the maximum tolerated cumulative dose (MTCD) and evaluate safety, activity, pharmacokinetics, and immunogenicity of moxetumomab pasudotox in children, adolescents, and young adults with ALL (n=55). Moxetumomab pasudotox was administered as a 30-minute intravenous infusion at doses of 5 to 50 µg/kg every other day (QOD) for six (Cohorts A and B) or 10 (Cohort C) doses, on 21-day cycles...
August 9, 2017: Blood
https://www.readbyqxmd.com/read/28793934/statin-therapy-causes-gut-dysbiosis-in-mice-through-a-pxr-dependent-mechanism
#20
Jose A Caparrós-Martín, Ricky R Lareu, Joshua P Ramsay, Jörg Peplies, F Jerry Reen, Henrietta A Headlam, Natalie C Ward, Kevin D Croft, Philip Newsholme, Jeffery D Hughes, Fergal O'Gara
BACKGROUND: Statins are a class of therapeutics used to regulate serum cholesterol and reduce the risk of heart disease. Although statins are highly effective in removing cholesterol from the blood, their consumption has been linked to potential adverse effects in some individuals. The most common events associated with statin intolerance are myopathy and increased risk of developing type 2 diabetes mellitus. However, the pathological mechanism through which statins cause these adverse effects is not well understood...
August 9, 2017: Microbiome
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