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HCV treatment failure

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 a treatment with 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...
October 19, 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
Youssef M Mosaad, Shereen S Metwally, Raghda E Farag, Zakeria F Lotfy, Hosam E AbdelTwab
BACKGROUND: Inconsistent results were reported on the association of TLRs polymorphisms with the risk of HCV infection and HCV-related diseases. OBJECTIVE: to assess the relation between TLR3 rs3775290, TLR7 rs17900 and TLR9 rs352140 SNPs and chronic HCV in the Egyptian cohort and to study their relation to interferon response. METHODS: TLR3 rs3775290, TLR7 rs179008 and TLR9 rs352140 gene polymorphisms were typed by RFLP for 100 patients with chronic HCV and 25 with HCC in addition to 100 healthy controls...
October 15, 2018: Immunological Investigations
Fabrizio Fabrizi, Piergiorgio Messa
Hepatitis C virus (HCV) infection leads to important morbidity and mortality through liver disease and extra-hepatic manifestations. Recent evidence suggests the role of HCV in developing chronic kidney disease (CKD); also, HCV adversely affects cardiovascular (CV) disease both in the general population and in patients with CKD. Areas covered: All-oral, interferon-free direct-acting antiviral agents (DAAs) are currently available; anti-HCV regimens based on DAAs are provided with high efficacy and safety and short treatment duration...
October 12, 2018: Expert Review of Clinical Pharmacology
Eiichi Ogawa, Norihiro Furusyo, Koichi Azuma, Makoto Nakamuta, Hideyuki Nomura, Kazufumi Dohmen, Takeaki Satoh, Akira Kawano, Toshimasa Koyanagi, Aritsune Ooho, Kazuhiro Takahashi, Masaki Kato, Shinji Shimoda, Eiji Kajiwara, Jun Hayashi
The real-world effectiveness and safety of all-oral direct-acting antivirals (DAAs) for chronic hepatitis C (HCV) infection and chronic kidney disease (CKD) have not been fully elucidated. This study assesses elbasvir (EBR) plus grazoprevir (GZR) for patients with HCV genotype 1 infection in the clinical setting, focusing on CKD stage 3-5D. This multicenter, real-world cohort study consisted of 282 Japanese patients who were treated with EBR (50 mg) plus GZR (100 mg) for a fixed 12-week duration. We evaluated the sustained viral response rate 12 weeks after the end of treatment (SVR12), longitudinal liver and renal parameters, and adverse effects according to the cirrhosis and CKD status...
November 2018: Antiviral Research
Takeji Umemura, Tomoo Yamazaki, Satoru Joshita, Ayumi Sugiura, Naoyuki Fujimori, Akihiro Matsumoto, Masao Ota, Eiji Tanaka
Although serum chemokine levels have been reported to influence the outcome of interferon-based treatment in patients with chronic hepatitis C, their effect on the hepatitis C virus (HCV) response to direct-acting antiviral agents (DAAs), which can achieve high rates of a sustained virological response (SVR), is largely unknown. To clarify this relationship, 9 chemokines (eotaxin, GRO-α, IL-8, IP-10, MCP-1, MIP-1α, MIP-1β, RANTES, and SDF-1α) were quantified before, during, and after DAA treatment using serum samples obtained from 57 patients with chronic hepatitis C...
October 5, 2018: Cytokine
Dzhamal T Abdurakhmanov, Teona P Rozina, Elena N Nikulkina, Ekaterina A Nabatchikova, Vladimir P Chulanov, Sergey V Moiseev
Despite very high efficacies of direct-acting antivirals (DAAs) reported in clinical trials, treatment failure in real-life practice can occur in 5-10% of cases and is mostly associated with emergence of resistance-associated substitutuions (RASs). Little is known about the efficacy of retreatment in these patients, especially in those with decompensated cirrhosis, and only a few retreatment studies have been performed so far. Here we present case reports of successful sofosbuvir based treatment in patients with advanced class B cirrhosis with prior PEG-IFN/ribavirin and all-oral DAA failure with multiclass drug resistance...
September 28, 2018: Antiviral Therapy
Beshoy Yanny, Sammy Saab, Francisco Durazo, Nyan Latt, Amanda Mitry, Mira Moris Mikhail, Ramy M Hanna, Antony Aziz, Amandeep Sahota
AIM: Results of recent studies have confirmed the efficacy of an 8-week course of ledipasvir/sofosbuvir (LDV/SOF) in patients who are non-cirrhotics, native to treatment, are infected with hepatitis C (HCV) genotype 1, and have HCV viral load < 6 million IU/mL. However, there are limited data on a shortened treatment course in patients who are over the age of 65. METHODS: A retrospective study was performed to examine the safety, tolerability, and sustained viral response rates (SVR) of the 8-week LDV/SOF therapy compared to the 12-week LDV/SOF therapy among non-cirrhotic, treatment-naïve, genotype 1 HCV patients with viral load < 6 million IU/mL who are 65 years of age or older...
September 27, 2018: Digestive Diseases and Sciences
Ameer Abutaleb, Kenneth E Sherman
Hepatitis C virus (HCV) treatment in HIV/HCV co-infected individuals has renewed relevance given the ongoing opioid crisis and rise of new HIV and HCV infections associated with injection drug use. Patients co-infected with HIV and HCV demonstrate increased rates of hepatic fibrosis, progression to liver failure, and liver-related mortality. HIV co-infection does not impact outcomes of current HCV treatments, and patients should be treated the same as HCV mono-infected persons, though attention to drug:drug interactions is required...
September 20, 2018: Hepatology International
Thuy Nguyen, Sepideh Akhavan, Fabienne Caby, Luminita Bonyhay, Lucile Larrouy, Anne Gervais, Pascal Lebray, Thierry Poynard, Yvon Calmus, Anne Simon, Marc-Antoine Valantin, Vincent Calvez, Anne-Geneviève Marcelin, Eve Todesco
BACKGROUND: More data on resistance of HCV genotype (GT) 3 and 4 to Direct-Acting Antivirals (DAAs) are still needed. We investigated presence of Resistance-Associated Substitutions (RASs) pre- and post-treatment and their emergence under DAAs in HCV GT3 and GT4 infected patients failing DAA regimens by next-generation sequencing (NGS). METHODS: Sanger sequencing and NGS were performed on NS5B and NS5A for plasma samples prior- and post-treatment of 13 patients...
September 17, 2018: International Journal of Antimicrobial Agents
Chen-Hua Liu, Yi-Jie Huang, Sien-Sing Yang, Chung-Hsin Chang, Sheng-Shun Yang, Hsin-Yun Sun, Chun-Jen Liu, Wen-Chun Liu, Tung-Hung Su, Hung-Chih Yang, Chun-Ming Hong, Tai-Chung Tseng, Pei-Jer Chen, Ding-Shinn Chen, Chien-Ching Hung, Jia-Horng Kao
Real-world data regarding the effectiveness and safety of generic sofosbuvir (SOF)-based interferon-free direct acting antiviral agents (DAAs) for patients with chronic hepatitis C virus (HCV) infection remain limited. A total of 517 chronic HCV-infected patients receiving 12 or 24 weeks of SOF-based therapies were retrospectively enrolled in 4 academic centers in Taiwan. The rate of sustained virologic response at week 12 off-therapy (SVR12 ) and that of treatment completion were assessed. The baseline characteristics and on-treatment HCV viral kinetics to predict SVR12 were analyzed...
September 12, 2018: Scientific Reports
Jong Man Kim, Kwang-Woong Lee, Dong-Hyun Sinn, Gyu-Seong Choi, Nam-Joon Yi, Choon Hyuck David Kwon, Kyung-Suk Suh, Jae-Won Joh
Purpose: The proportion of liver recipients with HCV is gradually increasing in Korea. Limited data are available regarding the efficacy of direct antiviral agents (DAAs) in liver transplant recipients in Asia. We aimed to assess the efficacy and safety of DAAs in HCV-infected liver recipients in Korea. Methods: Forty HCV-infected patients from 2 centers received DAAs in the pretransplant or posttransplant period between May 2015 and November 2016. Results: DAA was administered in the pretransplant period in 6 patients and the posttransplant period in 34 patients...
September 2018: Annals of Surgical Treatment and Research
María Eugenia Soria, Josep Gregori, Qian Chen, Damir García-Cehic, Meritxell Llorens, Ana I de Ávila, Nathan M Beach, Esteban Domingo, Francisco Rodríguez-Frías, María Buti, Rafael Esteban, Juan Ignacio Esteban, Josep Quer, Celia Perales
BACKGROUND: Despite the high sustained virological response rates achieved with current directly-acting antiviral agents (DAAs) against hepatitis C virus (HCV), around 5-10% of treated patients do not respond to current antiviral therapies, and basal resistance to DAAs is increasingly detected among treatment-naïve infected individuals. Identification of amino acid substitutions (including those in minority variants) associated with treatment failure requires analytical designs that take into account the high diversification of HCV in more than 86 subtypes according to the ICTV website (June 2017)...
September 3, 2018: BMC Infectious Diseases
Takehiro Akahane, Masayuki Kurosaki, Jun Itakura, Keiji Tsuji, Kouji Joko, Hiroyuki Kimura, Akihiro Nasu, Chikara Ogawa, Yuji Kojima, Chitomi Hasebe, Shuichi Wada, Yasushi Uchida, Tetsuro Sohda, Hideyuki Suzuki, Hideo Yoshida, Atsunori Kusakabe, Takashi Tamada, Haruhiko Kobashi, Akeri Mitsuda, Masahiko Kondo, Masaya Shigeno, Yasushi Ide, Atsuhiro Morita, Tadashi Kitamura, Takehiko Abe, Namiki Izumi
AIM: This study aimed to describe the real-world efficacy and safety of sofosbuvir (SOF) + ribavirin (RBV) for chronic hepatitis C, genotype 2. METHODS: This was a retrospective analysis of a nationwide, multicenter registry including 914 hepatitis C genotype 2 Japanese patients treated with SOF + RBV for 12 weeks. The rate of sustained virological response at 12 weeks after treatment (SVR12), incidence of adverse events, and changes in serological parameters was analyzed...
September 1, 2018: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Mohamed A Mekky, Mohamed O Abdel-Malek, Heba A Osman, Essam M Abdel-Aziz, Abdel-Kader A Hashim, Helal F Hetta, Khairy H Morsy
BACKGROUND: Till now, pooled data about the safety and efficacy of different direct-acting antiviral (DAAs) regimens in different renal situations are still under evaluation. AIM: To evaluate a real-life experience of the efficacy and safety of ombitasvir/paritaprevir/ritonavir plus ribavirin (OBV/PTV/r plus RIB) in patients with end-stage kidney disease (ESKD). PATIENTS AND METHODS: Between January 2017 and January 2018, an open-label multicenter prospective study was designed to enroll all consecutive patients with proven CHC genotype 4 infections and concomitant ESKD based on estimated glomerular filtration rate (eGFR) with (HD group) or without hemodialysis (non-HD group)...
August 27, 2018: Clinics and Research in Hepatology and Gastroenterology
Ashley N Matthew, Florian Leidner, Alicia Newton, Christos J Petropoulos, Wei Huang, Akbar Ali, Nese KurtYilmaz, Celia A Schiffer
Despite significant progress in hepatitis C virus (HCV) protease inhibitor (PI) drug design, resistance remains a problem causing treatment failure. Double-substitution variants, notably Y56H/D168A, have emerged in patients who fail therapy with a PI-containing regimen. The resistance conferred by Asp168 substitutions has been well characterized and avoided in newer inhibitors. However, an additional mutation at Tyr56 confers resistance to even the most robust inhibitors. Here, we elucidate the molecular mechanisms of resistance for the Y56H/D168A variant against grazoprevir (and four analogs), paritaprevir, and danoprevir through inhibition assays, co-crystal structures, and molecular dynamics simulations...
October 2, 2018: Structure
Nozomu Wada, Fusao Ikeda, Chizuru Mori, Koichi Takaguchi, Shin-Ichi Fujioka, Haruhiko Kobashi, Yoichi Morimoto, Kazuya Kariyama, Kosaku Sakaguchi, Noriaki Hashimoto, Akio Moriya, Mitsuhiko Kawaguchi, Hirokazu Miyatake, Hiroaki Hagihara, Junichi Kubota, Hiroki Takayama, Yasuto Takeuchi, Tetsuya Yasunaka, Akinobu Takaki, Yoshiaki Iwasaki, Hiroyuki Okada
Daclatasvir (DCV) + asunaprevir (ASV) combination therapy has become available for patients with hepatitis C virus (HCV) serogroup 1 infection. We studied the efficacy of this therapy by focusing on the factors associated with sustained virological responses (SVR) including resistance-associated variants (RAVs) and mixed infection of different HCV genotypes. We enrolled 951 HCV serogroup 1-positive patients who received this combination therapy at our hospital or affiliated hospitals. The presence of RAVs in non-structural (NS) regions 3 and 5A was analyzed by direct sequencing...
August 2018: Acta Medica Okayama
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