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HCV treatment failure

Luz Martín-Carbonero, Lourdes Domínguez-Domínguez, Lucía Bailón, Rafael Torres, Rafael Rubio, Raquel Ron, Francisco Moreno, Mikel Rico, Inmaculada Jimenez-Nacher, Juan González-García, Federico Pulido, María Luisa Montes
OBJECTIVE: Data of hepatitis C treatment with direct-acting antivirals (DAAs) in HIV infected patients are limited to a few number of antiretroviral therapies (ART). The aim of this study was to assess the effectiveness and safety of non-conventional ART as monotherapy or dual therapy (MDT) when combined with DAA. METHODS: Retrospective review of HIV/HCV-coinfected patients treated with DAAs during one year in 3 centers. Sustained virologic response 12 weeks after therapy (SVR) and maintenance of HIV viral suppression were compared between patients receiving triple ART (TT) or MDT...
November 23, 2018: Enfermedades Infecciosas y Microbiología Clínica
Claudia Minosse, Marina Selleri, Emanuela Giombini, Barbara Bartolini, Maria Rosaria Capobianchi, Stefano Cerilli, Laura Loiacono, Chiara Taibi, Gianpiero D'Offizi, Fiona McPhee, AnnaRosa Garbuglia
Background: The efficacy of direct-acting antivirals (DAAs) depends on the hepatitis C virus (HCV) genotype 4 (GT4) subtype which are used in the treatment of HCV. We aimed to retrospectively investigate the baseline prevalence of HCV NS5A and NS5B polymorphisms and their impact on virological outcome in GT4-infected patients treated with various DAA regimens. Patients and methods: Available plasma samples from HCV GT4-infected patients treated with different DAA regimens were analyzed at baseline and after treatment failure, where applicable...
2018: Infection and Drug Resistance
Rita Chelly Felix Tavares, Ana Cristina de Castro Amaral Feldner, João Renato Rebello Pinho, Fernanda de Mello Malta, Roberto José Carvalho-Filho, Rúbia Anita Ferraz Santana, Vanessa Fusco Duarte de Castro, Gregório Tadeu Fernando Dastoli, Juliana Custódio Lima, Maria Lucia Cardoso Gomes Ferraz
Background: Direct-acting antiviral agents (DAAs) permit the use of interferon (IFN)-free regimens to treat hepatitis C (HCV) in patients with chronic kidney disease (CKD) on hemo-dialysis (HD) or renal transplant (RTx) recipients, with excellent response rates and safety. However, the occurrence of basal or therapy-induced resistance-associated substitutions (RASs) to DAAs can result in treatment failure. The aim of this study was to estimate the prevalence of RASs to NS3A, NS5A and NS5B inhibitors, and particularly the Q80K polymorphism, in CKD patients on HD and RTx recipients infected with HCV...
2018: Infection and Drug Resistance
Stanislas Pol, Lucia Parlati, Michel Jadoul
Hepatitis C virus (HCV) infection is more prevalent and is associated with higher mortality in patients receiving dialysis and in kidney transplant recipients than in the general population. Kidney transplant recipients who are HCV-positive are also at higher risk of allograft and liver failure than are HCV-negative recipients. Moreover, HCV infection is associated with a higher incidence and faster progression of diabetes mellitus and chronic kidney disease (CKD), as well as a higher incidence of systemic (especially cardiovascular) complications...
November 19, 2018: Nature Reviews. Nephrology
Jacinta A Holmes, Charles Carlton-Smith, Arthur Y Kim, Emily O Dumas, Joelle Brown, Jenna L Gustafson, Georg M Lauer, Sakuni T Silva, Maxwell Robidoux, Daniel Kvistad, Nadia Alatrakchi, Pierre Tonnerre, Daniel E Cohen, Hongtao Zhang, Nancy S Shulman, Raymond T Chung
The role of the endogenous interferon (IFN) system has been well characterized during IFN-based therapy for chronic hepatitis C virus (HCV) infection; less is known for direct-acting antivirals (DAAs). In this phase 3b open-label study, we assessed changes in IFN-stimulated genes (ISGs) in non-cirrhotic treatment-naïve or pegIFN/RBV-experienced HCV-GT1a-infected patients receiving paritaprevir/ritonavir/ombitasvir+dasabuvir+ribavirin (PrOD+R) for 12 weeks. ISG expression was quantified from PBMCs at baseline, treatment weeks (TW)2, TW4, TW8, end-of-treatment (EOT) and at post-treatment week 12...
November 19, 2018: Journal of Viral Hepatitis
Benedetto Caroleo, Maria Cristina Caroleo, Antonio Cimellaro, Lidia Colangelo, Maria Perticone, Giulio Di Mizio, Giovambattista De Sarro, Luca Gallelli
Direct-acting a antiviral (DAA) are currently used in the treatment of chronic HCV infection. In patients with renal failure with Elbasvir/Grazoprevir (genotype 1 and 4) or Pibrentasvir/Glecaprevir (genotype 1-6) is advised and these documented both good safety and efficacy. In this manuscript we reported the development of cholestatic jaundice, during Pibrentasvir/Glecaprevir treatment, in a 86-year-old male with chronic HCV (genotype 2) infection and renal failure. At examination patient was jaundiced and suffered of a severe itch...
November 15, 2018: Current Drug Safety
Francesca Ceccherini-Silberstein, Valeria Cento, Velia Chiara Di Maio, Carlo Federico Perno, Antonio Craxì
The introduction of new multi-genotypic direct acting antivirals (DAA) in clinical practice has revolutionized HCV treatment, permitting the achievement of >95% rates of sustained virological response in many patients. However, virological failures can occur particularly if the treatments are sub optimal and/or with too short duration. Failure is often associated with development of resistance. The wide genetic variability in terms of different genotypes and subtypes, together with the natural presence and/or easy development of resistance during treatment, are intrinsic characteristics of HCV that may affect the treatment outcome and the chances of achieving a virological cure...
November 12, 2018: Current Opinion in Virology
Lawrence Serfaty, Ira Jacobson, Jürgen Rockstroh, Frederick L Altice, Peggy Hwang, Eliav Barr, Michael Robertson, Barbara Haber
European treatment guidelines for hepatitis C virus (HCV) infection recommend that people with genotype (GT)1a infection and baseline viral load ≤800,000 IU/mL receive elbasvir/grazoprevir (EBR/GZR) for 12 weeks, and those with baseline viral load >800,000 IU/mL receive EBR/GZR plus ribavirin for 16 weeks. This analysis was conducted to clarify whether baseline viral load can serve as an accurate, sensitive, or specific stratification factor for defining EBR/GZR regimens. In this post hoc, integrated analysis, participants with GT1a infection who received EBR 50 mg/GZR 100 mg for 12 weeks were stratified according to baseline viral load...
November 9, 2018: Journal of Viral Hepatitis
Claudia Lasagni, Laura Bigi, Andrea Conti, Giovanni Pellacani
PURPOSE: Biologic therapy in psoriatic patients with multiple comorbidities is challenging due to worsening of associated diseases and possible side effects of concomitant medications. MATERIALS AND METHODS: We describe three patients with multiple comorbidities documenting successful treatment of psoriasis with secukinumab following failure of multiple conventional and biologic DMARDs. RESULTS: The first case is an obese 59-year-old woman (HBV + with latent tuberculosis) with arterial hypertension and 12-year history of breast cancer...
November 7, 2018: Journal of Dermatological Treatment
B-H Jung, J-I Park, S-G Lee
BACKGROUND: Fibrosing cholestatic hepatitis (FCH) is an aggressive form of hepatitis C virus (HCV) recurrence after liver transplantation (LT). Most FCH cases are fatal, occurring as a secondary disease following rapidly progressive liver dysfunction and graft failure. We report a case of early-onset FCH after LT that was successfully treated using daclatasvir and asunaprevir. CASE REPORT: A 59-year-old woman underwent living donor LT for HCV-related liver cirrhosis...
November 2018: Transplantation Proceedings
Saba Khaliq, Syed Mohsin Raza
In Pakistan, the burden of the hepatitis C virus (HCV) infection is the second highest in the world with the development of chronic hepatitis. Interferon-based combination therapy with ribavirin was the only available treatment until a few years back, with severe side-effects and high failure rates against different genotypes of HCV. Interferon-free all-oral direct-acting antiviral agents (DAAs) approved by the FDA have revolutionized the HCV therapeutic landscape due to their efficiency in targeting different genotypes in different categories of patients, including treatment naïve, treatment failure and relapsing patients, as well as patients with compensated and decompensated cirrhosis...
November 5, 2018: Medicina
Cody Orr, Johannes Aartun, Henry Masur, Shyam Kottilil, Eric G Meissner
Treatment of chronic hepatitis C virus (HCV) infection with direct acting antivirals (DAAs) results in a sustained virologic response (SVR) in most patients. While highly efficacious, ~3-5% of patients do not achieve SVR despite having virus that appears susceptible. It is unclear whether host factors contribute to treatment failures, although innate and adaptive immunity may play a role. Previous studies showed that after DAA treatment, the composition of intrahepatic immune cells does not normalize relative to healthy volunteers, even in cases where SVR is achieved...
November 1, 2018: Journal of Viral Hepatitis
Fred Poordad, Mitchell L Shiffman, Wayne Ghesquiere, Alexander Wong, Gregory D Huhn, Florence Wong, Alnoor Ramji, Stephen D Shafran, Fiona McPhee, Rong Yang, Stephanie Noviello, Misti Linaberry
BACKGROUND: Optimal treatment for patients with hepatitis C virus (HCV) genotype-3 infection and liver cirrhosis remains a medical priority. Daclatasvir+sofosbuvir and ribavirin is a recommended option for such patients, but clinical trial data are lacking for treatment >16 weeks. METHODS: This was a single-arm, Phase III study of daclatasvir+sofosbuvir+ribavirin for 24 weeks in patients with compensated cirrhosis and HCV genotype-3 infection. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12); the primary objective was to demonstrate statistical superiority to historical SVR12 data for 12 weeks' daclatasvir+sofosbuvir without ribavirin in genotype-3-infected patients with cirrhosis (95% confidence interval [CI] lower bound >79...
November 1, 2018: Antiviral Therapy
Meena Sivasankaran, M Venkatadesikalu, V Mythili, Srinivas Sankaranarayanan, Dhaarani Jayaraman, Shivani Patel, Venkateswaran Vellaichamy Swaminathan, Ramya Uppuluri, Revathi Raj
Transfusion-transmitted hepatitis C is a major concern among thalassemia patients. Our aim is to estimate the prevalence of Hepatitis C infection among thalassemia patients and to assess the treatment response, adverse effects of Peg-interferon based regimen and the new direct-acting antiviral drugs. Patients with thalassemia receiving regular blood transfusions with positive anti HCV antibodies during a period from January 2012 to June 2017 were analyzed. Serial HCV viral load and genotype and liver function tests were performed...
October 2018: Indian Journal of Hematology & Blood Transfusion
Nathalie Scherz, Philip Bruggmann, Nathalie Brunner
BACKGROUND: Treating chronic hepatitis C virus (HCV) infection among PWID (people who inject drugs) is crucial to achieve the WHO goal of HCV elimination, as this population is highly affected and carries a high risk of transmission. The aim of our study was to provide real-life data on HCV treatment among PWID either in opioid agonist treatment (OAT) or in heroin-assisted treatment (HAT) in a low-threshold access primary care-based addiction medicine institution. METHODS: We conducted a retrospective chart analysis of patients treated with direct-acting antivirals (DAA) between 10/2014 and 08/2017 in the Arud outpatient clinics in Zurich, Switzerland...
October 24, 2018: International Journal on Drug Policy
Thomas F Baumert, Thomas Berg, Joseph K Lim, David R Nelson
Chronic infection with hepatitis C virus (HCV) is a major cause of liver disease and hepatocellular carcinoma worldwide. Following the discovery of HCV 3 decades ago, the identification of the structure of the viral proteins, combined with high-throughput replicon models, enabled the discovery and development of direct-acting antivirals. These agents have revolutionized care of patients, with cure rates of more than 90%. We review the status of direct-acting antiviral therapies for HCV infection and discuss remaining challenges...
October 17, 2018: Gastroenterology
Elisabetta Loggi, Ranka Vukotic, Pietro Andreone
Direct acting antivirals have completely changed the landscape of the treatment of chronic hepatitis C. The management of the few patients who relapse to direct acting antivirals requires a careful analysis of the chances to achieve therapeutic success with a second antiviral course. In this context, the usefulness of viral resistances testing, able to detect resistance-associated substitutions in the viral sequence, is at present a matter of debate. Areas covered: The role of resistance associated substitutions is examined through the evaluation of the data from clinical trials that have assessed the impact of viral resistances on the treatment outcome...
November 2018: Expert Review of Anti-infective Therapy
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
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
Shrikant Dashrath Warkad, Satish Balasaheb Nimse, Keum-Soo Song, Taisun Kim
According to the World Health Organization (WHO), 71 million people were living with Hepatitis C virus (HCV) infection worldwide in 2015. Each year, about 399,000 HCV-infected people succumb to cirrhosis, hepatocellular carcinoma, and liver failure. Therefore, screening of HCV infection with simple, rapid, but highly sensitive and specific methods can help to curb the global burden on HCV healthcare. Apart from the determination of viral load/viral clearance, the identification of specific HCV genotype is also critical for successful treatment of hepatitis C...
October 12, 2018: Sensors
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