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HCV treatment failure

C Masetti, R Lionetti, M Lupo, M Siciliano, V Giannelli, F R Ponziani, E Teti, C Dell'Unto, S Francioso, A Brega, M Montalbano, U Visco-Comandini, C Taibi, G Galati, U Vespasiani Gentilucci, A Picardi, M Andreoni, M Pompili, A M Pellicelli, G D'Offizi, A Gasbarrini, A De Santis, M Angelico
Risk of HCC in HCV cirrhotic patients treated with DAA is still debating. We investigated it in a large cohort. The cohort comprised 1045 cirrhotic patients who completed treatment with DAA, with a median follow up of 17.3 months after EOT, including 943 patients without history of HCC and 102 previously treated for HCC. The majority were males (59.9%), with compensated cirrhosis (88.8%), genotype 1b (44.7%). Univariate, multivariate analysis and Kaplan Meier curves were performed to detect predictors of HCC in patients with and without reduction in AFP during treatment...
August 16, 2018: Journal of Viral Hepatitis
Dominique L Braun, Benjamin Hampel, Roger Kouyos, Huyen Nguyen, Cyril Shah, Markus Flepp, Marcel Stöckle, Anna Conen, Charles Béguelin, Patrizia Künzler-Heule, Dunja Nicca, Patrick Schmid, Julie Delaloye, Mathieu Rougemont, Enos Bernasconi, Andri Rauch, Huldrych F Günthard, Jürg Böni, Jan S Fehr
Background: This study was performed to investigate the efficacy and safety of grazoprevir-elbasvir guided by baseline resistance-associated substitutions (RASs) in the Swiss HCVree Trial ( NCT02785666). Methods: We performed hepatitis C virus (HCV) RNA screening among all men who have sex with men (MSM) enrolled in the Swiss HIV Cohort Study. Individuals with replicating HCV genotype 1 or 4 infection were eligible for grazoprevir-elbasvir treatment...
August 13, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Christoph Sarrazin, Curtis L Cooper, Michael P Manns, K Rajender Reddy, Kris V Kowdley, Stuart K Roberts, Hadas Dvory-Sobol, Evguenia Svarovskia, Ross Martin, Gregory Camus, Brian P Doehle, Luisa M Stamm, Robert H Hyland, Diana M Brainard, Hongmei Mo, Stuart C Gordon, Marc Bourliere, Stefan Zeuzem, Steven L Flamm
BACKGROUND & AIMS: The pangenotypic direct-acting antiviral agents of sofosbuvir (SOF), velpatasvir (VEL), and voxilaprevir (VOX), inhibit distinct HCV targets: the NS5B polymerase, the NS5A protein, and NS3/4A protease, respectively. In Phase 3 studies, fixed dose combination of SOF/VEL/VOX administered for 12 weeks demonstrated a 96% SVR12 rate in NS5A inhibitor-experienced patients, and a 98% SVR12 rate in DAA-experienced patients who had not previously received an NS5A inhibitor...
August 8, 2018: Journal of Hepatology
Cameron Sikavi, Lisa Najarian, Sammy Saab
BACKGROUND: Clinical trials evaluating efficacy of direct-acting antiviral (DAA) therapies demonstrate sustained virologic response (SVR) rates greater than 90% in patients infected with hepatitis C (HCV) and human immunodeficiency virus (HIV). However, generalizability of this data to real-world coinfected populations is unknown. AIM: We aim to compare efficacy data from clinical trials to effectiveness data of real-world observational studies that evaluate oral interferon-free HCV treatment regimens in patients infected with HIV and HCV...
August 9, 2018: Digestive Diseases and Sciences
Norio Akuta, Hitomi Sezaki, Fumitaka Suzuki, Shunichiro Fujiyama, Yusuke Kawamura, Tetsuya Hosaka, Masahiro Kobayashi, Mariko Kobayashi, Satoshi Saitoh, Yoshiyuki Suzuki, Yasuji Arase, Kenji Ikeda, Hiromitsu Kumada
In real-world setting, no many information is probably available on the treatment efficacy with the combination of glecaprevir and pibrentasvir (G/P) as salvage therapy in failures to prior direct-acting antivirals (DAAs) regimens. Especially, the evolution of NS5A resistance-associated variants (RAVs) and treatment efficacy in patients, who received G/P for failures to prior treatment more than once, is unknown. 20 patients, who were introduced glecaprevir 300 mg/day and pibrentasvir 120 mg/day for 12 weeks in failures to prior DAAs regimens, could be evaluated sustained virological response at 12 weeks after end of treatment (SVR12)...
August 9, 2018: Journal of Medical Virology
Edward R Cachay, Lucas Hill, Francesca Torriani, Craig Ballard, David Grelotti, Abigail Aquino, W Christopher Mathews
Background: We estimated and characterized the proportion of patients living with HIV (PLWH) who missed hepatitis C (HCV) intake appointments and subsequently failed to establish HCV care. Methods: Logistic regression analyses were used to identify factors associated with missed HCV intake appointments and failure to establish HCV care among PLWH referred for HCV treatment between January 2014 and December 2017. In addition to demographics, variables included HIV treatment characteristics, type of insurance, liver health status, active alcohol or illicit drug use, unstable housing, and history of a mental health disorder (MHD)...
July 2018: Open Forum Infectious Diseases
J A Perez-Molina, F Pulido, S Di Giambenedetto, E Ribera, S Moreno, J Zamora, C Coscia, B Alejos, J Pitch, J M Gatell, A De Luca, J R Arribas
Background: Dual therapy (DT) with a ritonavir-boosted PI (PI/r) plus lamivudine has proven non-inferior (12% margin) to triple therapy (TT) with PI/r plus two nucleos(t)ide reverse transcriptase inhibitors [N(t)RTIs] in four clinical trials. It remains unclear whether DT is non-inferior based on the US FDA endpoint (virological failure with a margin of 4%) or in specific subgroups. Methods: We performed a systematic search (January 1990 to March 2017) of randomized controlled trials that compared switching of maintenance ART from TT to DT...
August 3, 2018: Journal of Antimicrobial Chemotherapy
Farhad Zamani, Hossein Ajdarkosh, Fahimeh Safarnezhad-Tameshkel, Azita Azarkeivan, Hossein Keyvani, Farshad Naserifar, Jamshid Vafaeimanesh
Context: Patients with thalassaemia are at risk of infections such as hepatitis C virus (HCV) due to their repeated blood transfusions; meanwhile, the treatment of thalassaemia patients who had developed HCV infection is a controversial issue. Aims: Although the effectiveness of direct-acting antivirals on HCV infection has been confirmed, their side-effects as well as effects on haematological factors due to the resultant need for blood transfusion remain to be further understood...
April 2018: Indian Journal of Medical Microbiology
Evangelista Sagnelli, Mario Starace, Carmine Minichini, Mariantonietta Pisaturo, Margherita Macera, Caterina Sagnelli, Nicola Coppola
BACKGROUND: Introduced in 2013-2014, the second- and third-wave directly acting antivirals (DAAs) have strongly enhanced the efficacy and tolerability of anti-HCV treatment, with a sustained virological response (SVR) in 90-95% of cases treated. The aim of this paper was to focus on the type and prevalence of viral strains with a reduced sensitivity to DAAs and on treatment choices for DAA-experienced patients. METHODS: The Medline was searched for "HCV infection", "HCV treatment", "Directly acting antivirals","HCV resistance"...
August 6, 2018: Infection
Niyaz Ali, Wajid Hussain, Azam Hayat, Tariq Shah, Ronghui Wen, Ifra Zeb, Attiya Abdul Malik, Rahdia Ramzan, Mujaddad-Ur Rehman, Ibrar Khan
BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are important causes of morbidity and mortality among haemodialysis (HD) patients and create problems in the management of patients in the renal dialysis units, as patients with chronic renal failure do not absolutely clear these viral infections. AIM: The aim of the study is molecular detection of HBV and HCV and their possible risk factors among the HD patients in northern Pakistan. MATERIALS AND METHODS: A cross-sectional study was conducted from November 2013 to June 2014...
August 3, 2018: European Journal of Gastroenterology & Hepatology
Preethi Krishnan, Tami Pilot-Matias, Gretja Schnell, Rakesh Tripathi, Teresa I Ng, Thomas Reisch, Jill Beyer, Tatyana Dekhtyar, Michelle Irvin, Wangang Xie, Lois Larsen, Federico J Mensa, Christine Collins
Over 2200 HCV genotype (GT)1-6 infected patients with or without cirrhosis who were treatment-naïve or experienced to interferon, ribavirin and/or sofosbuvir were treated with glecaprevir/pibrentasvir for 8, 12 or 16 weeks in 8 registrational phase 2/3 clinical studies. High SVR12 rates were achieved with <1% virologic failure (VF) rate. The prevalence of baseline polymorphisms (BP) in NS3 at amino acid positions 155 or 168 was low (<3%) in GT1, GT2, GT3, GT4, and GT6, while 41.9% of the GT5-infected patients had NS3-D168E; BPs were not detected at position 156 in NS3...
July 30, 2018: Antimicrobial Agents and Chemotherapy
Susanna Naggie, Meredith Clement, Sam Lusk, Anu Osinusi, Tiffany Himmel, Joseph E Lucas, Will J Thompson, Laura Dubois, M Arthur Moseley, Paul J Clark, Shyam Kottilil, Keyur Patel
PURPOSE: In the interferon era of hepatitis C virus (HCV) therapies, genotype/subtype, cirrhosis, prior treatment failure, sex, and race predicted relapse. Our objective was to validate a targeted proteomics platform of 17 peptides to predict sustained virologic response (SVR). EXPERIMENTAL DESIGN: Stored plasma from three, open-label, trials of HIV/HCV co-infected subjects receiving interferon-containing regimens was identified. LC-MS/MS was used to quantitate the peptides directly from plasma, and IL28B genotyping was completed using stored PBMC...
July 30, 2018: Proteomics. Clinical Applications
Stephanie Popping, Valeria Cento, Federico García, Francesca Ceccherini-Silberstein, Carole Seguin-Devaux, David Amc Vijver, Charles A Boucher
The World Health Organization (WHO) has declared that hepatitis C virus (HCV) should be eliminated as a public health threat. A key recommendation to reach this elimination goal, is to reduce new infections by 90% and liver-related mortality by 65%. Highly effective direct-acting antiviral agents (DAA) play a major role in this elimination. Unfortunately, DAA treatment fails approximately 2.5-5% of patients, often in the presence of resistance-associated substitutions (RAS). This could eventually lead to a total number of 1...
July 1, 2018: Journal of Virus Eradication
Ayumi Sugiura, Satoru Joshita, Takeji Umemura, Tomoo Yamazaki, Naoyuki Fujimori, Takefumi Kimura, Akihiro Matsumoto, Koji Igarashi, Yoko Usami, Shuichi Wada, Hiromitsu Mori, Soichiro Shibata, Kaname Yoshizawa, Susumu Morita, Kiyoshi Furuta, Atsushi Kamijo, Akihiro Iijima, Satoko Kako, Atsushi Maruyama, Masakazu Kobayashi, Michiharu Komatsu, Makiko Matsumura, Chiharu Miyabayashi, Tetsuya Ichijo, Aki Takeuchi, Yuriko Koike, Yukio Gibo, Toshihisa Tsukadaira, Hiroyuki Inada, Kendo Kiyosawa, Eiji Tanaka
Direct-acting antiviral (DAA) treatment can achieve a high sustained virological response (SVR) rate in patients with hepatitis C virus (HCV) infection regardless of a history of hepatocellular carcinoma (HCC [+]). We examined 838 patients (370 men, median age: 69 years) who were treated with DAAs for comparisons of clinical findings between 79 HCC (+) (9.4%) and 759 HCC (-) (90.6%) patients and associations with treatment outcome. Male frequency was significantly higher in the HCC (+) group (60.8% vs. 42.4%, p = 0...
July 25, 2018: Journal of Viral Hepatitis
Piotr Czubkowski, Jan Pertkiewicz, Małgorzata Markiewicz-Kijewska, Piotr Kaliciński, Małgorzata Rurarz, Irena Jankowska, Joanna Pawłowska
BACKGROUND AND AIM: The aim of the study was to assess efficacy and safety of endoscopic treatment in BS after pediatric LTx. METHODS: We retrospectively reviewed data of patients with DDA who developed BS and underwent ERCP. RESULTS: Of 189 transplanted patients with DDA, strictures developed in 30 (16%). In this subgroup, the median age at LTx was 14.7 (1.5-17.6) and follow-up period was 3.9 (1.3-11.3). ABS were in 76% and NABS in combination with ABS in 24% of patients...
July 24, 2018: Pediatric Transplantation
Faryal Khamis, Jaleela Al Noamani, Hamed Al Naamani, Ibrahim Al-Zakwani
Objectives: In 2015, the Joint United Nations Program on HIV/AIDS (UNAIDS) set a target that 90% of all people living with HIV will know their HIV status, 90% of those diagnosed will receive antiretroviral therapy, and 90% of those receiving antiretroviral therapy will have viral suppression by 2020. We sought to elucidate the epidemiological and clinical characteristics of HIV infected patients at the Infectious Diseases Clinic at Royal Hospital, Oman, with a focus on the UNAIDS 90-90-90 achieved rates...
July 2018: Oman Medical Journal
Frederick Lahser, Angela Galloway, Peggy Hwang, John Palcza, Joann Brunhofer, Janice Wahl, Michael Robertson, Eliav Barr, Todd Black, Ernest Asante-Appiah, Barbara Haber
BACKGROUND: In hepatitis C virus (HCV)-infected people who fail to achieve sustained virological response after receiving a direct-acting antiviral regimen, virological failure is almost always accompanied by the presence of resistance-associated substitutions (RASs) in the target protein(s). The aim of this long-term observational study was to evaluate the persistence of NS3/4A and NS5A RASs in participants with genotype (GT) 1 infection who relapsed following treatment with a grazoprevir-containing treatment regimen...
July 24, 2018: Antiviral Therapy
Goki Suda, Masayuki Kurosaki, Jun Itakura, Namiki Izumi, Yoshihito Uchida, Satoshi Mochida, Chitomi Hasebe, Masami Abe, Hiroaki Haga, Yoshiyuki Ueno, Ikuto Masakane, Kazumichi Abe, Atsushi Takahashi, Hiromasa Ohira, Ken Furuya, Masaru Baba, Yoshiya Yamamoto, Tomoe Kobayashi, Atsuhiko Kawakami, Kenichi Kumagai, Katsumi Terasita, Masatsugu Ohara, Naoki Kawagishi, Machiko Umemura, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
BACKGROUND: The prevalence of hepatitis C virus (HCV) infection in hemodialysis patients is high and results in a poor prognosis. Thus, safer and more effective treatment regimens are required. In this prospective multicenter study, we investigated the efficacy and safety of the novel HCV-NS5A-inhibitor, elbasvir, and protease inhibitor, grazoprevir in Japanese hemodialysis patients with genotype 1b HCV infection. METHODS: This study is registered at the UMIN Clinical Trials Registry as UMIN00002578...
July 17, 2018: Journal of Gastroenterology
Steven Flamm, K Rajender Reddy, Neddie Zadeikis, Tarek Hassanein, Bruce R Bacon, Andreas Maieron, Stefan Zeuzem, Marc Bourliere, Jose L Calleja, Matthew P Kosloski, Rajneet K Oberoi, Chih-Wei Lin, Yao Yu, Sandra Lovell, Dimitri Semizarov, Federico J Mensa
BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are commonly prescribed to treat acid-related disorders. Some direct-acting antiviral regimens for chronic hepatitis C virus (HCV) infection have reduced efficacy in patients taking concomitant acid-reducing agents, including PPIs, due to interactions between drugs. We analyzed data from 9 multicenter, phase 2 and 3 trials to determine the efficacy and pharmacokinetics of an HCV therapeutic regimen comprising glecaprevir and pibrentasvir (glecaprevir/pibrentasvir) in patients taking concomitant acid-reducing agents...
July 13, 2018: Clinical Gastroenterology and Hepatology
Vishnu Venugopal, Pranesh Padmanabhan, Rubesh Raja, Narendra M Dixit
Direct-acting antiviral agents (DAAs) for hepatitis C treatment tend to fare better in individuals who are also likely to respond well to interferon-alpha (IFN), a surprising correlation given that DAAs target specific viral proteins whereas IFN triggers a generic antiviral immune response. Here, we posit a causal relationship between IFN-responsiveness and DAA treatment outcome. IFN-responsiveness restricts viral replication, which would prevent the growth of viral variants resistant to DAAs and improve treatment outcome...
July 2018: PLoS Computational Biology
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