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Adel Abdel-Moneim, Alaa Aboud, Mohamed Abdel-Gabbar, Mohamed Zanaty, Mohamed Ramadan
BACKGROUND: The current standard of care for patients with chronic hepatitis C virus (HCV) infection is a combination of direct-acting antiviral agents (DAAs). However, rare clinical trials have been reported on the combination regimen of sofosbuvir (SOF) with ombitasvir, paritaprevir, and ritonavir (OBV/PTV/r) plus ribavirin (RBV) for treated patients with HCV genotype 4 (GT4) infection. AIMS: To clarify the retreatment efficacy and safety of the recent regimen, SOF with OBV/PTV/r + RBV, for chronic HCV GT4-experienced patients who failed treatment with DAA-based regimens...
March 15, 2018: Digestive Diseases and Sciences
Young-A Heo, Emma D Deeks
A fixed-dose combination of the hepatitis C virus (HCV) NS5B polymerase inhibitor sofosbuvir, the HCV NS5A inhibitor velpatasvir and the HCV NS3/4A protease inhibitor voxilaprevir (sofosbuvir/velpatasvir/voxilaprevir; Vosevi® ) is approved in the EU for the treatment of chronic HCV genotype 1, 2, 3, 4, 5 or 6 infection in adults. In the phase III POLARIS trials, in patients who had HCV genotype 1-6 infection with or without compensated cirrhosis, overall rates of sustained virological response at 12 weeks post-treatment (SVR12 ) with sofosbuvir/velpatasvir/voxilaprevir were high after 8 weeks of treatment in direct-acting antiviral (DAA)-naïve patients and 12 weeks of treatment in DAA-experienced patients...
March 15, 2018: Drugs
Soon Young Ko, Won Hyeok Choe
The advent of novel, direct-acting antiviral (DAA) regimens for hepatitis C viral (HCV) infection has revolutionized its treatment by producing a sustained virologic response of more than 95% with few side effects and no comorbidities in the general population. Until recently, ideal DAA regimens have not been available to patients with severe renal impairment and end-stage renal disease because there are limited data on the pharmacokinetics, safety, and efficacy of treatment in this unique population. In a hemodialysis context, identifying patients in need of treatment and preventing HCV transmission may also be a matter of concern...
March 16, 2018: Clinical and Molecular Hepatology
Ivan Schietroma, Giuseppe Corano Scheri, Claudia Pinacchio, Maura Statzu, Arnolfo Petruzziello, Vincenzo Vullo
Introduction: Globally, between 64 and 103 million people are chronically infected with Hepatitis C virus (HCV), with more than 4.6 million people in the United States and is associated with more than 15.000 deaths annually. Chronic infection can result in cirrhosis and hepatocellular carcinoma. Explanation: Epidemiological studies have indicated that persistent infection with hepatitis C virus (HCV) is a major risk for the development of hepatocellular carcinoma (HCC), mainly through chronic inflammation, cell deaths, and proliferation...
2018: Open Virology Journal
Ayana Suzuki, Mitsuyoshi Hirokawa, Aki Ito, Nami Takada, Miyoko Higuchi, Toshitetsu Hayashi, Seiji Kuma, Tsutomu Daa, Akira Miyauchi
The pathogenesis of thyroid lymphoepithelial cysts is controversial, and two hypotheses have been proposed, namely derivation from branchial-derived remnants or from squamous metaplasia of the follicular cells. The aim of this study was to clarify the pathogenesis of thyroid lymphoepithelial cysts. We performed pathological and immunohistochemical examination of 21 thyroid lymphoepithelial cysts, 13 non-neoplastic squamous metaplasia samples without thyroid carcinoma, 13 solid cell nests, and 14 lateral cervical cysts...
March 14, 2018: Endocrine Journal
Sofia R Bartlett, Penny Fox, Harris Cabatingan, Anissa Jaros, Carla Gorton, Rhondda Lewis, Eugene Priscott, Gregory J Dore, Darren B Russell
Micro-elimination of hepatitis C virus (HCV) infection through rapid uptake of government-funded direct-acting antiviral (DAA) therapy within an Australian prison setting is demonstrated. During a 22 month period, 119 patients initiated treatment for chronic HCV infection, with HCV in-prison viremic prevalence declining from 12% to 1%.
March 12, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
J von Felden, J Vermehren, P Ingiliz, S Mauss, T Lutz, K G Simon, H W Busch, A Baumgarten, K Schewe, D Hueppe, C Boesecke, J K Rockstroh, M Daeumer, N Luebke, J Timm, J Schulze Zur Wiesch, C Sarrazin, S Christensen
BACKGROUND: Twelve weeks of the pangenotypic direct-acting antiviral (DAA) combination sofosbuvir/velpatasvir (SOF/VEL) was highly efficient in patients with hepatitis C virus (HCV) genotype 3 (GT3) infection in the ASTRAL-3 approval study. However, presence of resistance-associated substitutions (RASs) in the HCV nonstructural protein 5A (NS5A) was associated with lower treatment response. AIM: To assess the efficacy and safety of SOF/VEL ± ribavirin (RBV) and the impact of NS5A RASs and RBV use on treatment outcome in HCV GT3 infection in a real-world setting...
March 14, 2018: Alimentary Pharmacology & Therapeutics
O El-Sherif, Z G Jiang, E B Tapper, K C Huang, A Zhong, A Osinusi, M Charlton, M Manns, N H Afdhal, K Mukamal, J McHutchison, D M Brainard, N Terrault, M P Curry
BACKGROUND & AIMS: Treatment with direct-acting antiviral (DAA) agents can reduce model for end-stage liver disease and Child-Pugh-Turcotte (CPT) scores in patients with decompensated cirrhosis caused by hepatitis C virus (HCV). However, many of these patients still die or require liver transplantation. We collected data on baseline features of patients and aimed to develop a scoring system to predict response to DAA therapy. METHODS: We performed a retrospective analysis of data from 4 trials of the effects of sofosbuvir-based therapy in patients with HCV-associated decompensated cirrhosis (502 of CPT class B and 120 of CPT class C)...
March 10, 2018: Gastroenterology
Narayan Ramamurthy, Emanuele Marchi, M Azim Ansari, Vincent Pedergnana, Angela Mclean, Emma Hudson, Rory Bowden, Chris C A Spencer, Ellie Barnes, Paul Klenerman
New directly acting antivirals (DAAs) provide very high cure rates in most patients infected by hepatitis C virus (HCV). However, some patient groups have been relatively harder to treat including those with cirrhosis or infected with HCV genotype 3. In the recent BOSON trial, genotype 3, cirrhotic patients receiving a 16 week course of sofosbuvir and ribavirin had a sustained virologic response rate (SVR) of around 50%. In cirrhotic patients, IFNL4 CC genotype was significantly associated with SVR. This genotype was also associated with a lower interferon-stimulated gene (ISG) signature in peripheral blood and in liver at baseline...
March 13, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Daniel Enosi Tuipulotu, Natalie E Netzler, Jennifer H Lun, Jason M Mackenzie, Peter A White
Norovirus infections are a significant health and economic burden globally, accounting for hundreds of millions of cases of acute gastroenteritis every year. In the absence of an approved norovirus vaccine, there is an urgent need to develop antivirals to treat chronic infections, and provide prophylactic therapy to limit viral spread during epidemics and pandemics. Toll-like receptor (TLR) agonists have been explored widely for their antiviral potential and several are progressing through clinical trials for the treatment of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and as adjuvants for norovirus virus-like particle (VLP) vaccines...
March 12, 2018: Antimicrobial Agents and Chemotherapy
Kelly H Schlendorf, Sandip Zalawadiya, Ashish S Shah, Mark Wigger, Chan Y Chung, Sarah Smith, Matthew Danter, Chun W Choi, Mary E Keebler, D Marshall Brinkley, Suzanne Brown Sacks, Henry Ooi, Roman Perri, Joseph A Awad, Samuel Lewis, Rachel Hayes, Heather O'Dell, Callie Darragh, Alicia Carver, Cori Edmonds, Shelley Ruzevich-Scholl, JoAnn Lindenfeld
BACKGROUND: Given the shortage of suitable donor hearts for cardiac transplantation, and the favorable safety and efficacy of current agents used to treat hepatitis C virus (HCV), our institution recently piloted transplantation of select patients using HCV-positive donors. METHODS: Between September 2016 and March 2017, 12 HCV-naive patients and 1 patient with a history of treated HCV underwent heart transplantation (HT) using hearts from HCV-positive donors after informed consent...
January 31, 2018: Journal of Heart and Lung Transplantation
Michael J Taunton, Robert T Trousdale, Rafael J Sierra, Ken Kaufman, Mark W Pagnano
BACKGROUND: The choice of surgical approach for THA remains controversial. Some studies suggest that the direct anterior approach (DAA) leads to less muscle damage than the miniposterior approach (MPA), but there is little high-quality evidence indicating whether this accelerates recovery, or whether this approach-which may be technically more demanding-is associated with component malposition or more complications. QUESTIONS/PURPOSES: (1) Does the DAA result in faster return to activities of daily living than the MPA? (2) Does the DAA have superior patient-reported outcome measures than the MPA? (3) Does the DAA result in improved radiographic outcomes than the MPA? (4) Does the DAA have a higher risk of complications than the MPA? METHODS: Between March 1, 2013, and May 31, 2016, 116 patients undergoing primary unilateral THA were randomized to either the DAA or MPA; 15 patients withdrew after randomization, and one died 6 months after surgery from a stroke unrelated to the procedure...
February 2018: Clinical Orthopaedics and related Research
Giovanni Damiani, Chiara Franchi, Paolo Pigatto, Andrea Altomare, Alessia Pacifico, Stephen Petrou, Sebastiano Leone, Maria Caterina Pace, Marco Fiore
AIM: To evaluate the outcomes in biological treatment and quality of life of psoriatic patients with chronic hepatitis C (CHC) treated with new Direct-Acting Antiviral agents (DAAs) compared to pegylated interferon-2α plus ribavirin (P/R) therapy. METHODS: This is a retrospective study involving psoriatic patients in biological therapy who underwent anti-hepatitis C virus (HCV) treatment at the Department of Dermatology Galeazzi Orthopaedic Institute Milan, Italy from January 2010 to November 2017...
February 27, 2018: World Journal of Hepatology
Amna Subhan Butt, Fatima Sharif, Shahab Abid
Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality worldwide. Chronic hepatitis C virus infection (HCV) is the most common cause of HCC in many European countries, Japan and Pakistan. Introduction of the new direct acting antivirals (DAAs) has revolutionized the management of HCV worldwide, with high rates of sustained virologic response in patients who could not have tolerated the previous interferon based treatments. However, recently there have been reports raising caution about the long term effects of DAAs, particularly a possible increased risk of HCC...
February 27, 2018: World Journal of Hepatology
Megumi Kawakubo, Yuichiro Eguchi, Michiaki Okada, Shinji Iwane, Satoshi Oeda, Taiga Otsuka, Syunya Nakashita, Norimasa Araki, Akemi Koga
Objective The aim of this study was to determine if direct-acting antiviral (DAA) treatment with daclatasvir (DCV) plus asunaprevir (ASV) for 24 weeks influenced the health-related quality of life (HRQOL) at 12 and 24 weeks after treatment initiation (end of treatment [EOT]). Methods This was a prospective, longitudinal study comparing the HRQOL of patients receiving DAA treatment at 12 weeks after treatment initiation and EOT with the HRQOL at baseline. We used a Japanese-validated version of the 8-item Short Form Health Survey (SF-8) to assess the HRQOL of patients...
March 9, 2018: Internal Medicine
Pil Soo Sung, Eun Byul Lee, Dong Jun Park, Angelo Lozada, Jeong Won Jang, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon
Background/Aims: Hepatitis C virus (HCV) replicates in the peripheral blood mononuclear cells (PBMCs), leading to the production of type I interferons (IFNs). It is well known that the gene expression profile of PBMC is similar to that of the liver. The present study explored the dynamic gene expression profile of PBMCs collected from HCV-infected patients undergoing direct-acting antiviral (DAA) therapy. Methods: A prospective cohort comprising 27 patients under DAA therapy was formed...
March 12, 2018: Clinical and Molecular Hepatology
Maria C Sorbo, Valeria Cento, Velia C Di Maio, Anita Y M Howe, Federico Garcia, Carlo F Perno, Francesca Ceccherini-Silberstein
Nowadays, due to the development of potent Direct-Acting Antiviral Agents (DAAs) that specifically target NS3, NS5A and NS5B viral proteins, several new and highly efficacious options to treat chronic Hepatitis C virus (HCV) infection are available. The natural presence of resistance associated substitutions (RASs), as well as their rapid emergence during incomplete drug-pressure, are intrinsic characteristics of HCV that greatly affect treatment outcome and the chances to achieve a virolgical cure. To date, a high number of RASs in NS3, NS5A, and NS5B have been associated in vivo and/or in vitro with reduced susceptibility to DAAs, but no comprehensive RASs list is available...
February 21, 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
Saverio G Parisi, Samantha Andreis, Carlo Mengoli, Nicola Menegotto, Silvia Cavinato, Renzo Scaggiante, Massimo Andreoni, Giorgio Palù, Monica Basso, Anna Maria Cattelan
Soluble CD163, soluble CD14 and cellular HIV-1-DNA levels reflect two different aspects of HIV infection: immune activation and the reservoir of infected cells. The aim of this study was to describe their relationships in a cohort of HIV-HCV co-infected patients successfully treated for both HCV and HIV infections. Fifty-five patients were recruited and studied prior to the start of direct-acting antivirals (DAAs) (T0), at week 12 of DAA treatment (T1) and 24 weeks after T0 (T2). The subjects were classified as having undetectable plasma HIV viraemia (UV) or low-level viraemia (LLV) in the 18 months before T2...
March 9, 2018: Medical Microbiology and Immunology
Robert J Wong, Mamta K Jain, George Therapondos, Mitchell L Shiffman, Onkar Kshirsagar, Christopher Clark, Mae Thamer
OBJECTIVE: Despite availability of highly effective direct acting antivirals (DAA), barriers in access to these therapies limit our ability to achieve HCV eradication. We aim to evaluate overall rates and predictors of HCV treatment across four community-based health-care systems focusing on race/ethnicity and insurance-specific disparities. METHODS: We retrospectively evaluated all adults with chronic HCV at four health care systems from 1 January 2011 to 28 February 2017, which included a large proportion of ethnic minorities, two safety-net systems, and a broad payer mix across four states...
March 9, 2018: American Journal of Gastroenterology
Victoire Bouveau, Thomas-Xavier Haen, Joel Poupon, Christophe Nich
BACKGROUND: Function after revision total hip arthroplasty (THA) in failed metal-on-metal (MoM) hip resurfacing arthroplasty (HRA) is variable, but post-operative complication rates are reportedly high. We hypothesized HRA conversion to THA using the direct anterior approach (DAA) would be associated with optimal outcome. METHODS: Seventeen MoM-HRAs in 15 patients (seven males, eight females) were revised through the DAA. The mean age was 45 years (28-59 yrs)...
March 8, 2018: International Orthopaedics
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