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https://www.readbyqxmd.com/read/28734831/effects-of-all-oral-anti-viral-therapy-on-hvpg-and-systemic-hemodynamics-in-patients-with-hepatitis-c-virus-associated-cirrhosis
#1
Sabela Lens, Edilmar Alvarado, Zoe Mariño, María-Carlota Londoño, Elba LLop, Javier Martinez, Jose Ignacio Fortea, Luís Ibañez, Xavier Ariza, Anna Baiges, Adolfo Gallego, Rafael Bañares, Angela Puente, Agustín Albillos, Jose Luís Calleja, Xavier Torras, Virginia Hernández-Gea, Jaume Bosch, Cándid Villanueva, Xavier Forns, Juan Carlos García-Pagán
BACKGROUND & AIMS: Patients with hepatitis C virus (HCV)-associated cirrhosis and clinical significant portal hypertension (CSPH, hepatic venous pressure gradient [HVPG] 10 mmHg or greater), despite achieving sustained virological response (SVR) to therapy, remain at risk of liver decompensation. We investigated hemodynamic changes following SVR in patients with CSPH and whether liver stiffness measurements (LSMs) can rule out the presence of CSPH. METHODS: We performed a multicenter prospective study of 226 patients with HCV-associated cirrhosis and CSPH who had SVR to interferon-free therapy at 6 Liver Units in Spain...
July 19, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28733665/human-intrahepatic-cd69%C3%A2-%C3%A2-cd8-t-cells-have-a-tissue-resident-memory-t-cell-phenotype-with-reduced-cytolytic-capacity
#2
Femke Stelma, Annikki de Niet, Marjan J Sinnige, Karel A van Dort, Klaas P J M van Gisbergen, Joanne Verheij, Ester M M van Leeuwen, Neeltje A Kootstra, Hendrik W Reesink
Tissue resident memory T cells (TRM) have been identified in various tissues, however human liver TRM to date remain unidentified. TRM can be recognized by CD69 and/or CD103 expression and may play a role in the pathology of chronic hepatitis B (CHB) and hepatitis C virus infection (CHC). Liver and paired blood mononuclear cells from 17 patients (including 4 CHB and 6 CHC patients) were isolated and CD8+ T cells were comprehensively analysed by flowcytometry, immunohistochemistry and qPCR. The majority of intrahepatic CD8+ T cells expressed CD69, a marker used to identify TRM, of which a subset co-expressed CD103...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733609/suppression-of-hbv-replication-by-the-expression-of-nickase-and-nuclease-dead-cas9
#3
Takeshi Kurihara, Takasuke Fukuhara, Chikako Ono, Satomi Yamamoto, Kentaro Uemura, Toru Okamoto, Masaya Sugiyama, Daisuke Motooka, Shota Nakamura, Masato Ikawa, Masashi Mizokami, Yoshihiko Maehara, Yoshiharu Matsuura
Complete removal of hepatitis B virus (HBV) DNA from nuclei is difficult by the current therapies. Recent reports have shown that a novel genome-editing tool using Cas9 with a single-guide RNA (sgRNA) system can cleave the HBV genome in vitro and in vivo. However, induction of a double-strand break (DSB) on the targeted genome by Cas9 risks undesirable off-target cleavage on the host genome. Nickase-Cas9 cleaves a single strand of DNA, and thereby two sgRNAs are required for inducing DSBs. To avoid Cas9-induced off-target mutagenesis, we examined the effects of the expressions of nickase-Cas9 and nuclease dead Cas9 (d-Cas9) with sgRNAs on HBV replication...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733564/the-clinical-features-and-treatment-outcome-of-chronic-hepatitis-c-with-pegylated-interferon-and-ribavirin-in-routine-care
#4
S S Tan, Z Adlin Nadia
AIM: To describe the clinical characteristic of hepatitis C (HCV) patients and the results of pegylated interferon and ribavirin (PegIFN/RBV) therapy in a routine clinical practice. METHODS: A retrospective review of consecutive HCV patients treated with PegIFN/RBV in 2004 to 2012. RESULTS: A total of 273 patients received treatment. The mean age was 44.16 ± 10.5 years and 76% were male. The top 2 self-reported risks were blood or blood product transfusion before 1994 and injection drug use, found in 57...
June 2017: Medical Journal of Malaysia
https://www.readbyqxmd.com/read/28732153/hepatitis-b-and-c-viruses-and-biologics
#5
P Grewal, R Sanghera
Hepatitis B virus (HBV) and hepatitis C virus (HCV) are common, worldwide viral illnesses that potentially impact the clinician's ability to manage patients with immunosuppressive medications such as biological therapy. In light of recent literature reviews, patients with HBV and HCV should be referred to a hepatologist or infectious disease expert prior to initiation of biological therapy.
July 2017: Skin Therapy Letter
https://www.readbyqxmd.com/read/28732085/point-of-care-screening-for-hepatitis-b-virus-infection-in-pregnant-women-at-an-antenatal-clinic-a-south-african-experience
#6
Nafiisah Chotun, Wolfgang Preiser, Christoffel Johannes van Rensburg, Pedro Fernandez, Gerhard Barnard Theron, Dieter Glebe, Monique Ingrid Andersson
BACKGROUND & AIMS: Elimination of HIV and syphilis mother-to-child transmission (MTCT) has received much attention but little consideration has been given to the possibility of elimination of HBV MTCT. In sub-Saharan Africa, HBV vertical transmission continues to be reported and it remains an important public health problem. This study aimed to assess the feasibility of screening pregnant women for HBV using a point-of-care (POC) test and implementing interventions to prevent HBV MTCT...
2017: PloS One
https://www.readbyqxmd.com/read/28732046/qualitative-differences-in-cellular-immunogenicity-elicited-by-hepatitis-c-virus-t-cell-vaccines-employing-prime-boost-regimens
#7
Wendy G Tan, Iryna Zubkova, Alla Kachko, Frances Wells, Heiko Adler, Gerd Sutter, Marian E Major
T-cell based vaccines have been considered as attractive candidates for prevention of hepatitis C virus (HCV) infections. In this study we compared the magnitude and phenotypic characteristics of CD8+ T-cells induced by three commonly used viral vectors, Adenovirus-5 (Ad5), Vaccinia virus (VV) and Modified Vaccinia Ankara (MVA) expressing the HCV NS3/4A protein. C57/BL6 mice were primed with DNA expressing NS3/4A and boosted with each of the viral vectors in individual groups of mice. We then tracked the vaccine-induced CD8+ T-cell responses using pentamer binding and cytokine production analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28732019/rate-of-hepatitis-c-viral-clearance-by-human-livers-in-human-patients-liver-transplantation-modeling-primary-infection-and-implications-for-studying-entry-inhibition
#8
Michael G Hughes, William W Tucker, Sreelatha Reddy, Michael E Brier, David Koch, Craig J McClain, Colleen B Jonsson, Nobuyuki Matoba, Donghoon Chung
To better understand the dynamics of early hepatitis C virus (HCV) infection, we determined how rapidly non-cirrhotic HCV-uninfected liver allografts clear HCV from the circulation of cirrhotic HCV-infected patients at the time of transplantation but before administration of immunosuppression. Specifically, we characterized serum HCV kinetics during the first 90 min of reperfusion for 19 chronically HCV-infected patients transplanted with an HCV-uninfected liver by measuring serum viral load immediately prior to reperfusion (t = 0) and then every 15 min for a total of 90 min (t = 90)...
2017: PloS One
https://www.readbyqxmd.com/read/28731786/high-post-treatment-%C3%AE-fetoprotein-levels-and-aspartate-aminotransferase-to-platelet-ratio-index-predict-hepatocellular-carcinoma-in-hepatitis-c-virus-decompensated-cirrhotic-patients-with-sustained-virological-response-after-antiviral-therapy
#9
Fanpu Ji, Rui Zhou, Wenjun Wang, Dan Bai, Caini He, Zhifang Cai, Yuan Shen, Shengbang Wang, Hong Deng, Zongfang Li
Although eradication of hepatitis C virus (HCV) decreases the risk of hepatocellular carcinoma (HCC) development, a considerable level of risk remains in cirrhotic patients with advanced liver disease. Yet, data for the effect of serum markers on HCC development in this population after viral eradication are still lacking. Seventy-eight consecutive patients with HCV infection and decompensated cirrhosis were administered interferon-based regimens at our hospital between August 2008 and December 2013. Thirty-four achieved sustained virological response and were enrolled in the study...
July 21, 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28730136/early-diagnosis-of-abcb11-spectrum-liver-disorders-by-next-generation-sequencing
#10
Su Jeong Lee, Jung Eun Kim, Byung-Ho Choe, An Na Seo, Han-Ik Bae, Su-Kyeong Hwang
PURPOSE: The goal of this study was the early diagnosis of ABCB11 spectrum liver disorders, especially those focused on benign recurrent intrahepatic cholestasis and progressive familial intrahepatic cholestasis. METHODS: Fifty patients presenting neonatal cholestasis were evaluated to identify underlying etiologies. Genetic analysis was performed on patients suspected to have syndromic diseases or ABCB11 spectrum liver disorders. Two families with proven ABCB11 spectrum liver disorders were subjected to genetic analyses to confirm the diagnosis and were provided genetic counseling...
June 2017: Pediatric Gastroenterology, Hepatology & Nutrition
https://www.readbyqxmd.com/read/28729862/rad51-interacts-with-non-structural-3-protein-of-hepatitis-c-virus-and-regulates-viral-production
#11
Kidong Son, Tram T T Nguyen, Jae-Woong Choi, Long V Pham, Trang T D Luong, Yun-Sook Lim, Soon B Hwang
Hepatitis C virus (HCV) is a leading cause of chronic liver disease affecting over 170 million people worldwide. Chronic infection with HCV progresses to liver fibrosis, cirrhosis, and hepatocellular carcinoma. HCV exploits host cellular factors for viral propagation. To investigate the cellular factors required for HCV propagation, we screened a siRNA library targeting human cell cycle genes using cell culture grown HCV-infected cells. In the present study, we selected and characterized a gene encoding Rad51...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28729054/isosorbide-based-peptidomimetics-as-inhibitors-of-hepatitis-c-virus-serine-protease
#12
Aline C Portela, Thalita G Barros, Camilo H da S Lima, Luiza R S Dias, Pedro H R de A Azevedo, Anna Sophia C L Dantas, Ronaldo Mohana-Borges, Gustavo T Ventura, Sergio Pinheiro, Estela M F Muri
Hepatitis C infection is a cause of chronic liver diseases such as cirrhosis and carcinoma. The current therapy for hepatitis C has limited efficacy and low tolerance. The HCV encodes a serine protease which is critical for viral replication, and few protease inhibitors are currently on the market. In this paper, we describe the synthesis and screening of novel isosorbide-based peptidomimetic inhibitors, in which the compounds 1d, 1e, and 1i showed significant inhibition of the protease activity in vitro at 100µM...
July 8, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28728835/a-multiplex-pcr-for-detection-of-six-viruses-in-ducks
#13
Yongjuan Wang, Shanyuan Zhu, Weiming Hong, Anping Wang, Weiyong Zuo
In this study, six pairs of specific primers that can amplify DNA fragments of different sizes were designed and synthesized according to viral protein gene sequences published in GenBank. Then, a multiplex PCR method was established for rapid detection of duck hepatitis virus 1, duck plague virus, duck Tembusu virus, muscovy duck parvovirus, muscovy duck reovirus, and duck H9N2 avian influenza virus, and achieve simple and rapid detection of viral diseases in ducks. Single PCR was used to confirm primer specificity, and PCR conditions were optimized to construct a multiplex PCR system...
July 17, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28727946/confounding-by-single-nucleotide-polymorphism-rs117648444-p70s-affects-the-association-of-interferon-lambda-locus-variants-with-response-to-interferon-%C3%AE-ribavirin-therapy-in-patients-with-chronic-genotype-3-hepatitis-c-virus-infection
#14
Anand Bhushan, Sumona Ghosh, Samsiddhi Bhattacharjee, Sreedhar Chinnaswamy
Genome-wide association studies discovered interferon lambda (IFNL or IFN-λ) locus on chromosome 19 to be involved in clearance of chronic hepatitis C virus (HCV) infection in patients following interferon-α-ribavirin (IFN-RBV) therapy. Subsequent studies established a dinucleotide polymorphism rs368234815, as the prime causal variant behind this association. The ΔG allele of this variant gives rise to a new IFNL gene, IFNL4, coding for IFN-λ4 whose activity paradoxically associates with lesser viral clearance rates...
July 20, 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28727243/filamin-a-expression-predicts-early-recurrence-of-hepatocellular-carcinoma-after-hepatectomy
#15
Matteo Donadon, Luca Di Tommaso, Cristiana Soldani, Barbara Franceschini, Alfonso Terrone, Antonio Mimmo, Eleonora Vitali, Massimo Roncalli, Andrea Lania, Guido Torzilli
BACKGROUND & AIMS: Recurrence of hepatocellular carcinoma (HCC) after hepatectomy is very high. A predictive marker of early recurrence (ER) capable of personalizing follow-up and developing a new target therapy would be beneficial. The overexpression of Filamin-A (FLNA), a cytoskeleton protein with scaffolding properties, has recently been associated with progression in tumors. The aim of this study was to test the expression of FLNA in a cohort of patients operated for HCC. METHODS: A retrospective cohort of patients who underwent hepatic resection at Humanitas Clinical and Research Center between January 2004 and December 2014 was analyzed...
July 20, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28725041/a-screen-for-novel-hepatitis-c-virus-rdrp-inhibitor-identifies-a-broad-spectrum-antiviral-compound
#16
Abhilasha Madhvi, Smita Hingane, Rajpal Srivastav, Nishant Joshi, Chandru Subramani, Rajagopalan Muthumohan, Renu Khasa, Shweta Varshney, Manjula Kalia, Sudhanshu Vrati, Milan Surjit, C T Ranjith-Kumar
Hepatitis C virus (HCV) is a global pathogen and infects more than 185 million individuals worldwide. Although recent development of direct acting antivirals (DAA) has shown promise in HCV therapy, there is an urgent need for the development of more affordable treatment options. We initiated this study to identify novel inhibitors of HCV through screening of compounds from the National Cancer Institute (NCI) diversity dataset. Using cell-based assays, we identified NSC-320218 as a potent inhibitor against HCV with an EC50 of 2...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28725030/a-practical-model-evaluating-antiviral-cytokines-by-natural-killer-cells-in-treatment-na%C3%A3-ve-patients-with-chronic-hepatitis-b-virus-infection
#17
Xiaoyan Li, Yurong Gu, Xiaobo Guo, Lin Gu, Liang Zhou, Xiaojuan Wu, Xueqin Wang, Zania Stamataki, Yuehua Huang
Natural killer (NK) cells play a major role in anti-viral immunity as first line defense during hepatitis B infection, particularly in untreated patients whose T cells functions are profoundly impaired. Cytokine interferon (IFN)-γ and tumor necrosis factor (TNF)-α produced by NK cells are important anti-viral factors. However, there is lack of a quantifiable model to evaluate cytokine responses by NK cells. In this study, almost half of the patients (47.9%) beyond treatment criteria had high cytokine activity, although it was lower than those recommended for antiviral therapy (78...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724915/quinolinate-phosphoribosyltransferase-is-an-antiviral-host-factor-against-hepatitis-c-virus-infection
#18
Zhilong Wang, Yanhang Gao, Chao Zhang, Haiming Hu, Dongwei Guo, Yi Xu, Qiuping Xu, Weihong Zhang, Sisi Deng, Pingyun Lv, Yan Yang, Yanhua Ding, Qingquan Li, Changjiang Weng, Xinwen Chen, Sitang Gong, Hairong Chen, Junqi Niu, Hong Tang
HCV infection can decrease NAD(+)/NADH ratio, which could convert lipid metabolism to favor HCV replication. In hepatocytes, quinolinate phosphoribosyl transferase (QPRT) catabolizes quinolinic acid (QA) to nicotinic acid mononucleotide (NAMN) for de novo NAD synthesis. However, whether and how HCV modulates QPRT hence the lipogenesis is unknown. In this work, we found QPRT was reduced significantly in livers of patients or humanized C/O(Tg) mice with persistent HCV infection. Mechanistic studies indicated that HCV NS3/4A promoted proteasomal degradation of QPRT through Smurf2, an E3 ubiquitin-protein ligase, in Huh7...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724761/isg15-modulates-type-i-interferon-signaling-and-antiviral-response-during-hepatitis-e-virus-replication
#19
Harini Sooryanarain, Adam J Rogers, Dianjun Cao, Mary Etna R Haac, Yogesh A Karpe, Xiang-Jin Meng
Hepatitis E virus (HEV), a single-stranded positive-sense RNA virus, generally causes a self-limiting acute viral hepatitis, although chronic HEV infection has recently become a significant clinical problem in immunocompromised individuals especially in solid organ transplant recipients. Innate immunity, via type-I interferon (IFN) response, plays an important role during initial stages of a viral infection. ISG15, an IFN-induced ubiquitin-like protein, is known to have an immunomodulatory role, as well as can impart a direct antiviral effect against a wide spectrum of virus families...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28723858/maternal-hepatitis-b-virus-infection-and-pregnancy-outcomes-a-hospital-based-case-control-study-in-wuhan-china
#20
Zhihua Wan, Aifen Zhou, Huiping Zhu, Xiaofang Lin, Dan Hu, Songxu Peng, Bin Zhang, Yukai Du
GOALS: To examine the impact of maternal hepatitis B virus infection on pregnancy outcomes. BACKGROUND: Studies regarding hepatitis B virus infection and pregnancy outcomes are limited with inconsistent results, and none of them have evaluated the effect of maternal viral load in pregnancy on pregnancy outcomes. STUDY: A hospital-based case-control study was conducted. In total, 1728 hepatitis B surface antigen (HBsAg)-positive women who delivered consecutively at Wuhan Women and Children Medical and Healthcare Center, Wuhan, China, from June 2008 to May 2015, were compared with 1497 HBsAg-negative women giving birth in the same hospital during the same period who were randomly identified and selected from the computerized medical record database in parallel...
July 18, 2017: Journal of Clinical Gastroenterology
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