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Hepatitis c genotype 4

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https://www.readbyqxmd.com/read/28107583/chronic-hepatitis-c-and-chronic-kidney-disease-advances-limitations-and-unchartered-territories
#1
Manuel Mendizabal, K Rajender Reddy
Over the past few years, treatment options for chronic hepatitis C virus (HCV) infection have evolved dramatically. The current approved interferon-free direct-acting antiviral (DAA) regimens have been shown to be safe and effective with sustained virologic response (SVR) rates of >90% in most patients. Unique issues yet remain such as the challenges in patients with impaired renal function or decompensated cirrhosis. Patients with stage 4-5 chronic kidney disease (CKD) have a higher prevalence of HCV infection compared with the general population...
January 20, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28106726/discrepancy-between-hepatitis-c-virus-genotypes-and-ns4-based-serotypes-association-with-their-subgenomic-sequences
#2
Nan Nwe Win, Shingo Nakamoto, Tatsuo Kanda, Hiroki Takahashi, Azusa Takahashi-Nakaguchi, Shin Yasui, Masato Nakamura, Shuang Wu, Fumio Imazeki, Shigeru Mikami, Osamu Yokosuka, Tohru Gonoi, Hiroshi Shirasawa
Determination of hepatitis C virus (HCV) genotypes plays an important role in the direct-acting agent era. Discrepancies between HCV genotyping and serotyping assays are occasionally observed. Eighteen samples with discrepant results between genotyping and serotyping methods were analyzed. HCV serotyping and genotyping were based on the HCV nonstructural 4 (NS4) region and 5'-untranslated region (5'-UTR), respectively. HCV core and NS4 regions were chosen to be sequenced and were compared with the genotyping and serotyping results...
January 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106531/preclinical-characterization-of-the-novel-hcv-ns3-protease-inhibitor-gs-9256
#3
Huiling Yang, Chris Yang, Yujin Wang, Gerry Rhodes, Margaret Robinson, Guofeng Cheng, Xiaoping Qi, Hongmei Mo, Yang Tian, Rowchanak Pakdaman, X Christopher Sheng, Choung U Kim, William E Delaney
BACKGROUND: GS-9256 is an inhibitor of hepatitis C virus (HCV) NS3 protease with a macrocyclic structure and novel phosphinic acid pharmacophore. METHODS: Key preclinical properties of GS-9256 including in vitro antiviral activity, cross-resistance, and pharmacokinetic properties were investigated in non-human species. RESULTS: In genotype (GT) 1b Huh-luc cells with a replicon encoding luciferase, GS-9256 had a mean EC50 value of 20.0 nM, with minimal cytotoxicity...
January 20, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28102906/filling-the-gap-between-clinical-trials-and-real-life-in-the-treatment-of-severe-hcv-recurrence-after-liver-transplantation
#4
Patrizia Burra, Alberto Zanetto
In this issue of Transplant International, Herzer et al. report the results obtained in a real-world European cohort of 87 patients with severe recurrent hepatitis C (HCV) after liver transplantation (LT), who were treated with a compassionate use of daclatasvir (DCV) plus registered sofosbuvir (SOF), with or without ribavirin (RBV). The vast majority of patients were HCV genotype 1, though the sample included a few with genotypes 3 and 4. It is noteworthy that 37/87 patients (42.5%) had cirrhosis (and 16/37 patients [43%] had Child-Pugh B/C decompensated cirrhosis)...
January 19, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28102520/us-fda-perspective-on-elbasvir-grazoprevir-treatment-for-patients-with-chronic-hepatitis-c-virus-genotype-1-or-4-infection
#5
Sarita D Boyd, LaRee Tracy, Takashi E Komatsu, Patrick R Harrington, Prabha Viswanathan, Jeff Murray, Adam Sherwat
Elbasvir/grazoprevir demonstrated high sustained virologic response rates 12 weeks after the end of treatment (SVR12) across five clinical trials in subjects infected with chronic hepatitis C virus (HCV) genotype 1, including those with advanced chronic kidney disease (CKD), and GT4. Despite favorable results overall, the US Food and Drug Administration (FDA) encountered challenging regulatory issues due to the limitations of clinical trial data in certain subpopulations. In GT1a-infected subjects, baseline NS5A resistance-associated polymorphisms emerged as the strongest baseline characteristic associated with diminished SVR12 rates following 12 weeks of elbasvir/grazoprevir treatment...
January 19, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28101128/simultaneous-determination-of-newly-developed-antiviral-agents-in-pharmaceutical-formulations-by-hplc-dad
#6
Nourah Zoman Al-Zoman, Hadir Mohamed Maher, Amal Al-Subaie
BACKGROUND: Ombitasvir/paritaprevir/ritonavir/dasabuvir (Viekira Pak(®)) are the newest medicines approved for use in the treatment of hepatitis C virus (HCV) and are available in tablet form as an oral combination. Specifically, these agents are indicated in the treatment of HCV in patients with genotype 1 infection. Due to the therapeutic importance and increased use of Viekira Pak, proper methods for its determination in bulk and pharmaceutical formulations must be developed. RESULTS: The present study describes the development and validation of a simple, rapid, selective and economical reverse phase high performance liquid chromatography-diode array detection (HPLC-DAD) method for the simultaneous determination of paritaprevir (PAR), ombitasvir (OMB), dasabuvir(DAS) and ritonavir (RIT) in bulk and pharmaceutical preparations...
2017: Chemistry Central Journal
https://www.readbyqxmd.com/read/28099338/liver-steatosis-in-children-with-chronic-hepatitis-b-and-c-prevalence-predictors-and-impact-on-disease-progression
#7
Maria Pokorska-Śpiewak, Barbara Kowalik-Mikołajewska, Małgorzata Aniszewska, Magdalena Pluta, Bożena Walewska-Zielecka, Magdalena Marczyńska
Only scarce data on liver steatosis in children with chronic hepatitis B and C (CHB and CHC) are available. The objective of this study was to evaluate the prevalence, predictors, and impact of hepatic steatosis on children with CHB and CHC. A total of 78 patients aged 11.5 ± 3.4 years were included: 30 (38%) had CHB, and 48 (62%) had CHC. Steatosis was scored on a 5-point scale, as follows: absent; minimal (≤5% hepatocytes affected), mild (6-33%), moderate (34-66%), and severe (>66%). Stepwise logistic regression was used to determine the factors associated with steatosis and moderate-to-severe steatosis...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28097103/efficacy-and-safety-of-daclatasvir-in-hepatitis-c-an-overview
#8
REVIEW
Nesrine Gamal, Stefano Gitto, Pietro Andreone
Hepatitis C virus (HCV) infection is a growing public health concern, with 184 million people infected worldwide. During the past decade, interferon has been the backbone of HCV treatment, even though it remains far from ideal. The latest development of the new direct antivirals has drastically changed the treatment approach for chronic hepatitis C (CHC). Inhibitors of the HCV NS5A region have garnered remarkable interest among treating physicians, due to their high potency and favourable safety profile. In particular, treatment with daclatasvir (DCV) has yielded high rates of vriologic response in patients infected with genotype (Gt) 1 and Gt 3, when used in combination with other antivirals of a different class, such as sofosbuvir...
December 28, 2016: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/28087069/safety-tolerability-and-antiviral-effect-of-rg-101-in-patients-with-chronic-hepatitis-c-a-phase-1b-double-blind-randomised-controlled-trial
#9
Meike H van der Ree, J Marleen de Vree, Femke Stelma, Sophie Willemse, Marc van der Valk, Svend Rietdijk, Richard Molenkamp, Janke Schinkel, Ad C van Nuenen, Ulrich Beuers, Salah Hadi, Marten Harbers, Eva van der Veer, Kai Liu, John Grundy, Amy K Patick, Adam Pavlicek, Jacqueline Blem, Michael Huang, Paul Grint, Steven Neben, Neil W Gibson, Neeltje A Kootstra, Hendrik W Reesink
BACKGROUND: miR-122 is an important host factor for hepatitis C virus (HCV) replication. The aim of this study was to assess the safety and tolerability, pharmacokinetics, and antiviral effect of a single dose of RG-101, a hepatocyte targeted N-acetylgalactosamine conjugated oligonucleotide that antagonises miR-122, in patients with chronic HCV infection with various genotypes. METHODS: In this randomised, double-blind, placebo-controlled, multicentre, phase 1B study, patients were randomly assigned to RG-101 or placebo (7:1)...
January 10, 2017: Lancet
https://www.readbyqxmd.com/read/28076298/comparison-of-abbott-realtime-genotype-ii-genematrix-restriction-fragment-mass-polymorphism-and-sysmex-hiscl-hcv-gr-assays-for-hepatitis-c-virus-genotyping
#10
Mi-Soon Han, Yongjung Park, Hyon-Suk Kim
BACKGROUND: Hepatitis C virus (HCV) genotype is a predictive marker for treatment response. We sequentially evaluated the performances of two nucleic acid amplification tests (NAATs) and one serology assay for HCV genotype: Abbott RealTime genotype II (RealTime II), GeneMatrix restriction fragment mass polymorphism (RFMP), and Sysmex HISCL HCV Gr (HISCL Gr). METHODS: We examined 281 clinical samples with three assays. The accuracy was assessed using the HCV Genotype Performance Panel PHW204 (SeraCare Life Sciences) for two NAATs...
January 11, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28072888/clinical-and-virological-predictors-of-sustained-response-with-an-interferon-based-simeprevir-regimen-for-patients-with-chronic-genotype-1-hepatitis-c-virus-infection
#11
Gianpiero D'Offizi, Calogero Cammà, Chiara Taibi, Michael Schlag, Karin Weber, Maria Palma, Ralph DeMasi, Katrien Janssen, James Witek, Raffaella Lionetti
Simeprevir plus peg-interferon/ribavirin (PR) is approved to treat chronic hepatitis C (HCV) genotype 1 (GT1) and GT4 infection. This study aimed to assess baseline and on-treatment the factors predictive of sustained virologic response 12 weeks post-treatment (SVR12) in patients receiving 12 weeks of simeprevir plus PR followed by 12 or 36 weeks of PR. Data from participants in four studies (QUEST-1, QUEST-2, ATTAIN and PROMISE) were pooled to examine the efficacy and safety of simeprevir+PR in HCV GT1 patients...
January 9, 2017: New Microbiologica
https://www.readbyqxmd.com/read/28070899/sofosbuvir-based-treatment-regimens-real-life-results-of-14-409-chronic-hcv-genotype-4-patients-in-egypt
#12
A Elsharkawy, R Fouad, W El Akel, M El Raziky, M Hassany, G Shiha, M Said, I Motawea, T El Demerdash, S Seif, A Gaballah, Y El Shazly, M A M Makhlouf, I Waked, A O Abdelaziz, A Yosry, M El Serafy, M Thursz, W Doss, G Esmat
BACKGROUND: Chronic hepatitis C virus infection is one of the most important health problems in Egypt. The Ministry of Health's National Treatment Programme introduced sofosbuvir-based therapy in October 2014. AIM: To assess the clinical effectiveness and predictors of response to SOF-based treatment regimens, either dual therapy, with SOF/ribavirin (RBV) for 6 months or triple therapy with SOF/peg-IFN-alfa-2a/RBV for 3 months, in a cohort of patients treated in National Treatment Programme affiliated centres in Egypt...
January 9, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28068153/prediction-of-fibrosis-progression-rate-in-patients-with-chronic-hepatitis-c-genotype-4-role-of-cirrhosis-risk-score-and-host-factors
#13
Tarek Besheer, Mahmoud El-Bendary, Hatem Elalfy, Mohamed Abd El-Maksoud, Mohamed Salah, Khaled Zalata, Wagdi Elkashef, Heba Elshahawy, Doaa Raafat, Wafaa Elemshaty, Noha Almashad, Hosam Zaghloul, Abdel-Hady El-Gilany, Ahmed Abdel Khalek Abdel Razek, Mohamed Abd Elwahab
The rate of liver fibrosis progression in chronic hepatitis C (CHC) patients is highly variable and affected by different factors. This study aimed to assess the role of cirrhosis risk score (CRS) based on 7 genetic variants (7 single-nucleotide polymorphisms [SNPs]) and host factors (age and sex) in the prediction of the rate of fibrosis progression in CHC. Duration of infection was determined in 115 patients. The fibrosis progression rate (FPR) per year was calculated as the ratio between fibrosis stage and the duration of infection...
January 9, 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28067632/hcv-genotype-1-subtypes-and-resistance-associated-substitutions-in-drug-naive-and-in-direct-acting-antiviral-treatment-failure-patients
#14
Yael Gozlan, Ziv Ben-Ari, Roy Moscona, Rachel Shirazi, Avia Rakovsky, Arij Kabat, Ella Veizman, Tania Berdichevski, Peretz Weiss, Oranit Cohen-Ezra, Yoav Lurie, Inna Gafanovich, Marius Braun, Michal Cohen-Naftaly, Amir Shlomai, Oren Shibolet, Ehud Zigmond, Eli Zuckerman, Michal Carmiel-Haggai, Assy Nimer, Rawi Hazzan, Yaakov Maor, Yona Kitay-Cohen, Yonat Shemer, Zipi Kra-Oz, Lisita Schreiber, Ofer Peleg, Ella Mendelson, Orna Mor
BACKGROUND: Direct-acting antiviral (DAA) treatment regimens and response rates of patients with hepatitis C virus (HCV) genotype 1 (GT1) are currently considered subtype-dependent. Identification of clinically relevant resistance-associated substitutions (RASs) in the NS3 and NS5A proteins at baseline and in DAA failures, may also impact clinical decisions. METHODS: In a multicenter cohort study (n=308), NS3 or NS5B sequencing (n=248) was used to discriminate between GT1 subtypes...
January 9, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28061762/the-effectiveness-of-daclatasvir-based-therapy-in-european-patients-with-chronic-hepatitis-c-and-advanced-liver-disease
#15
Jim Young, Nina Weis, Harald Hofer, William Irving, Ola Weiland, Emiliano Giostra, Juan Manuel Pascasio, Lluis Castells, Martin Prieto, Roelien Postema, Cinira Lefevre, David Evans, Heiner C Bucher, Jose Luis Calleja
BACKGROUND: There is limited evidence for the effectiveness of daclatasvir in patients whose hepatitis C threatens their life expectancy. The Named Patient Program in Europe included patients with advanced chronic hepatitis C, a life expectancy of less than 12 months and no other treatment options. METHODS: A retrospective multi-country cohort of patients with chronic hepatitis C who received daclatasvir as part of the Named Patient Program in Austria, Denmark, Spain, Sweden, Switzerland and the United Kingdom...
January 7, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28056030/efficacy-of-a-12-week-simeprevir-plus-peginterferon-ribavirin-pr-regimen-in-treatment-na%C3%A3-ve-patients-with-hepatitis-c-virus-hcv-genotype-4-gt4-infection-and-mild-to-moderate-fibrosis-displaying-early-on-treatment-virologic-response
#16
Tarik Asselah, Christophe Moreno, Christoph Sarrazin, Michael Gschwantler, Graham R Foster, Antonio Craxí, Peter Buggisch, Faisal Sanai, Ceyhun Bicer, Oliver Lenz, Gino Van Dooren, Catherine Nalpas, Isabelle Lonjon-Domanec, Michael Schlag, Maria Buti
BACKGROUND: HCV GT4 accounts for up to 20% of HCV infections worldwide. Simeprevir, given for 12 weeks as part of a 24- or 48-week combination regimen with PR is approved for the treatment of chronic HCV GT4 infection. Primary study objectives were assessment of efficacy and safety of simeprevir plus PR in treatment-naïve patients with HCV GT4 treated for 12 weeks. Primary efficacy outcome was sustained virologic response 12 weeks post-treatment (SVR12). Additional objectives included investigation of potential associations of rapid virologic response and baseline factors with SVR12...
2017: PloS One
https://www.readbyqxmd.com/read/28052633/hepatitis-c-efficacy-and-safety-in-real-life
#17
REVIEW
Robert Flisiak, Joanna Pogorzelska, Marta Flisiak-Jackiewicz
Interferon-free combinations were registered in 2014 and 2015 for the treatment of chronic HCV infection. As a result, real-world experience has been gathered in the last year and this paper presents data available in September 2016. Real-world studies on the efficacy of the ledipasvir/sofosbuvir (LDV/SOF)±ribavirin (RBV) regimen showed a sustained virologic response (SVR) rate of between 91% and 98%. The SVR rate in the 13858 patients included in this paper was 94%, and 92% in the 3506 patients with cirrhosis...
January 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28052021/serum-hepatitis-b-core-antibody-titer-use-in-screening-for-significant-fibrosis-in-treatment-na%C3%A3-ve-patients-with-chronic-hepatitis-b
#18
Min-Ran Li, Huan-Wei Zheng, Jian-Hua Lu, Shun-Mao Ma, Li-Hong Ye, Zhi-Quan Liu, Hai-Cong Zhang, Yun-Yan Liu, Ying Lv, Yan Huang, Er-Hei Dai, Dian-Xing Sun
BACKGROUND: Previous studies have revealed that hepatitis B core antibody (anti-HBc) levels vary throughout the different phases of treatment-naïve chronic hepatitis B (CHB) patients and can be used as a predictor of treatment response in both interferon-α and nucleoside analogue therapies. However, few data have been published regarding the relationship between quantitative anti-HBc (qAnti-HBc) levels and liver fibrosis in patients with CHB. RESULTS: A total of 489 HBeAg-positive (HBeAg (+)) and 135 HBeAg-negative (HBeAg (-)) patients were recruited...
December 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/28039331/hepatic-deletion-of-x-box-binding-protein-1-impairs-bile-acid-metabolism-in-mice
#19
Xiaoying Liu, Anne S Henkel, Brian E LeCuyer, Susan C Hubchak, Matthew J Schipma, Eric Zhang, Richard M Green
The unfolded protein response (UPR) is an adaptive response to endoplasmic reticulum stress and the inositol-requiring enzyme 1α/X-box binding protein 1 (IRE1α/XBP1) pathway of the UPR is important in lipid metabolism. However, its role in bile acid metabolism remains unknown. We demonstrate that liver-specific Xbp1 knockout (LS-Xbp1(-/-)) mice had a 45% reduction in total bile acid pool. LS-Xbp1(-/-) mice had lower serum 7α-hydroxy-4-cholesten-3-one (C4) levels compared to Xbp1(fl/fl) mice, indicating reduced CYP7A1 synthetic activity...
December 30, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/28036111/hepatic-ifnl4-expression-is-associated-with-non-response-to-interferon-based-therapy-through-the-regulation-of-basal-interferon-stimulated-gene-expression-in-chronic-hepatitis-c-patients
#20
Miyako Murakawa, Yasuhiro Asahina, Fukiko Kawai-Kitahata, Mina Nakagawa, Sayuri Nitta, Satoshi Otani, Hiroko Nagata, Shun Kaneko, Yu Asano, Tomoyuki Tsunoda, Masato Miyoshi, Yasuhiro Itsui, Seishin Azuma, Sei Kakinuma, Yasuhito Tanaka, Sayuki Iijima, Kaoru Tsuchiya, Namiki Izumi, Shuju Tohda, Mamoru Watanabe
Single nucleotide polymorphisms (SNPs) within or near interferon lambda 4 (IFNL4) gene located upstream of IFNL3 are associated with response to anti-HCV therapy both in interferon (IFN)-based and IFN-free regimens. IFNL4 encodes IFNλ4, a newly discovered type III IFN, and its expression is controlled by rs368234815-TT/ΔG, which is in strong linkage disequilibrium (LD) with other tag SNPs within or near IFNL4 such as rs12979860 and rs8099917. Intrahepatic expression levels of IFN-stimulated genes (ISGs) affect the responsiveness to IFNα and are also associated with IFNL4 genotype...
December 30, 2016: Journal of Medical Virology
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