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Janina Bruening, Lisa Lasswitz, Pia Banse, Sina Kahl, Carine Marinach, Florian W Vondran, Lars Kaderali, Olivier Silvie, Thomas Pietschmann, Felix Meissner, Gisa Gerold
Hepatitis C virus (HCV) and the malaria parasite Plasmodium use the membrane protein CD81 to invade human liver cells. Here we mapped 33 host protein interactions of CD81 in primary human liver and hepatoma cells using high-resolution quantitative proteomics. In the CD81 protein network, we identified five proteins which are HCV entry factors or facilitators including epidermal growth factor receptor (EGFR). Notably, we discovered calpain-5 (CAPN5) and the ubiquitin ligase Casitas B-lineage lymphoma proto-oncogene B (CBLB) to form a complex with CD81 and support HCV entry...
July 2018: PLoS Pathogens
Mostafa Elhelbawy, Wael Abdel-Razek, Ayman Alsebaey, Mohamed Hashim, Hassan Elshenawy, Imam Waked
BACKGROUND: Insulin resistance (IR) is a common complication in chronic hepatitis C virus (HCV) patients. The impact of IR on outcome of therapy with direct antivirals has not been studied. AIM: The aim was to assess the impact of direct-acting antiviral (DAA) therapy on IR status in chronic HCV patients. PATIENTS AND METHODS: A total of 511 patients [mean age: 50.7±10.4 years, 29.7% pegylated interferon and ribavirin (RBV) experienced] were enrolled...
July 18, 2018: European Journal of Gastroenterology & Hepatology
Youki Ueda, Weilin Gu, Hiromichi Dansako, Hye-Sook Kim, Sayaka Yoshizaki, Nobuaki Okumura, Tomohiro Ishikawa, Hironori Nishitsuji, Fumihiro Kato, Takayuki Hishiki, Shinya Satoh, Koji Ishii, Michiaki Masuda, Kunitada Shimotohno, Masanori Ikeda, Nobuyuki Kato
The chemically synthesized endoperoxide compound N-89 and its derivative N-251 were shown to have potent antimalarial activity. We previously demonstrated that N-89 and N-251 potently inhibited the RNA replication of hepatitis C virus (HCV), which belongs to the Flaviviridae family. Since antimalarial and anti-HCV mechanisms have not been clarified, we were interested whether N-89 and N-251 possessed the activity against viruses other than HCV. In this study, we examined the effects of N-89 and N-251 on other flaviviruses (dengue virus and Japanese encephalitis virus) and hepatitis viruses (hepatitis B virus and hepatitis E virus)...
September 2018: Biochemistry and Biophysics Reports
Abdulkareem M Albekairy, Wesam S Abdel-Razaq, Abdulmalik M Alkatheri, Tariq M Al Debasi, Nouf E Al Otaibi, Amjad M Qandil
The use of immunosuppressants to reduce the likelihood of acute graft rejections is a cornerstone in the post-transplantation management of recipients. However, these agents were always associated with increased risk of deleterious effects such as infections vulnerability and comorbidities. The objective of this review is to discuss the impact of different immunosuppression strategies used in liver transplant recipients (LTRs) on the recurrence of hepatitis C virus (HCV) infections after transplantation. Traditionally, corticosteroids were a mainstay in immunosuppressive regimens in LTRs...
July 2018: International Journal of Health Sciences
Ahmed Khaled Tawfik, Ahmed Mustafa Amin, Mohamed Yousef, Noha Mohamed El-Sayd, Heba Elashry, Mahmoud Elkadeem, Sherief Abd-Elsalam
Background and aims: Immunoregulatory cytokines influence the persistence of hepatitis C virus (HCV) chronic infection and the extent of liver damage. Interleukin-1 (IL-1) plays an important role in the inflammatory process. Some studies have demonstrated that IL-1α production was impaired in patients with chronic infections of HCV, implying that IL-1α may play a role in viral clearance. The aim of this study was to evaluate the serum level of proinflammatory cytokine IL-1α in patients with chronic hepatitis C (CHC)...
2018: Journal of Inflammation Research
Benjamin Maasoumy, Peter Buggisch, Stefan Mauss, Klaus H W Boeker, Tobias Müller, Rainer Günther, Tim Zimmermann, Michael P Manns, Christoph Sarrazin, Dietrich Hüppe, Heiner Wedemeyer, Johannes Vermehren
BACKGROUND & AIMS: AASLD/IDSA treatment guidelines for hepatitis C virus (HCV) infection state that testing for quantitative HCV RNA can be considered at the end of antiviral treatment (EOT) with interferon-free regimens. However, it remains unclear how to respond to a detectable or even quantifiable HCV RNA result. The aim of this study was to analyze the frequency and predictive value of detectable and quantifiable HCV RNA results at the EOT in patients with HCV genotype 1 infection treated with ledipasvir (LDV) and sofosbuvir (SOF) ± ribavirin (RBV) in a large real world cohort...
July 18, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
Afrodite Psaros Einberg, Björn Fischler
The use of interferon free, oral direct acting antiviral (DAA) combination therapy has in the last few years rapidly changed the care for adult patients with chronic hepatitis C virus (HCV) infection (1). Their strong efficacy, with sustained viral response (SVR) rates of 90-95% and a very low burden of side effects, has prompted considerations for paediatric usage (2). Results from the first controlled paediatric trials are equally promising and subsequently combination therapy, with sofosbuvir and ledipasvir for genotypes 1 and 4 and sofosbuvir and ribavirin for genotypes 2 and 3, is now licensed for patients above 12 years of age (2)...
July 19, 2018: Acta Paediatrica
Asmaa Nafady, Hanaa Nafady-Hego, Nadia M Abdelwahab, Radwa H N Eltellawy, Nagla Hassan Abu Faddan
BACKGROUND: Hepatitis C virus (HCV) -specific immune response is believed to play a crucial role in viral clearance. There is, nevertheless, no reliable parameter to monitor this immune response or predict chronic HCV infection development METHOD: An observational case-control study was done to identify such parameters, peripheral blood mononuclear cells from 57 children with chronic HCV was systemically phenotyped and the serum level of Interferon gamma and interleukin (IL) -17 was measured...
July 19, 2018: European Journal of Clinical Investigation
Laura Sinigaglia, Ségolène Gracias, Elodie Décembre, Matthieu Fritz, Daniela Bruni, Nikaïa Smith, Jean-Philippe Herbeuval, Annette Martin, Marlène Dreux, Frédéric Tangy, Nolwenn Jouvenet
Plasmacytoid dendritic cells (pDCs) are specialized in the production of interferons (IFNs) in response to viral infections. The Flaviviridae family comprises enveloped RNA viruses such as Hepatitis C virus (HCV) and Dengue virus (DENV). Cell-free flaviviridae virions poorly stimulate pDCs to produce IFN. By contrast, cells infected with HCV and DENV potently stimulate pDCs via short-range delivery of viral RNAs, which are either packaged within immature virions or secreted exosomes. We report that cells infected with Yellow fever virus (YFV), the prototypical flavivirus, stimulated pDCs to produce IFNs in a TLR7- and cell contact- dependent manner...
July 18, 2018: Scientific Reports
Donald P Rice, Michelle A Ordoveza, Ann M Palmer, George Y Wu, Lisa M Chirch
Direct-acting antiviral therapy is safe and cost-effective for the treatment of hepatitis C virus (HCV) infection. However, variability in drug payment rules represents a barrier to treatment that may disproportionately affect certain populations. We conducted a retrospective cohort study among HIV/HCV coinfected and HCV monoinfected patients using Kaplan-Meier and Fisher's exact test to analyze the time from the prescription of a direct-acting antiviral agent to delivery to the patient. Variables with significance p < ...
July 18, 2018: AIDS Care
Deborah D'Aliberti, Irene Cacciola, Cristina Musolino, Giuseppina Raffa, Roberto Filomia, Angela Alibrandi, Salvatore Benfatto, Concetta Beninati, Carlo Saitta, Domenico Giosa, Orazio Romeo, Giovanni Raimondo, Teresa Pollicino
BACKGROUND: Hepatitis C virus (HCV) NS3 resistance-associated substitutions (RASs) reduce HCV susceptibility to protease inhibitors. Little is known about NS3 RASs in viral isolates from the liver of chronic hepatitis C (CHC) patients infected with HCV genotype-1a (G1a). AIM: The objective of this work was to study NS3 variability in isolates from the serum and liver of HCV-G1a-infected patients naïve to direct-acting antivirals (DAAs). METHODS: NS3 variability of HCV-G1a isolates from the serum and liver of 11 naïve CHC patients, and from sera of an additional 20 naïve CHC patients, was investigated by next-generation sequencing...
July 18, 2018: Intervirology
Hong-Van Tieu, Oliver Laeyendecker, Vijay Nandi, Rebecca Rose, Reinaldo Fernandez, Briana Lynch, Donald R Hoover, Victoria Frye, Beryl A Koblin
Emerging sexually transmitted hepatitis C virus (HCV) epidemics among men who have sex with men (MSM) have been reported worldwide, with higher HCV infection rates among those who are HIV-infected. This study aims to determine prevalence of recent and chronic HCV infections among community-recruited MSM in New York City (NYC), map HCV infections by home, social, and sexual neighborhoods, and identify clusters of genetically linked HCV variants using phylogenetic analysis. The NYC M2M study recruited MSM via modified time-space, venue-based sampling and internet/mobile app-based recruitment during 2010-13...
2018: PloS One
Laura Iliescu, Adriana Mercan-Stanciu, Elena Simona Ioanitescu, Letitia Toma
BACKGROUND AND PURPOSE: Hepatitis C virus (HCV) can induce both hepatic and extrahepatic malignancies. A strong association between HCV and non-Hodgkin lymphomas (NHLs) has been demonstrated. The purpose of this article is to give emphasis on the clinical and imagistic particularities of the hepatitis C-associated NHL, revealing the importance of ultrasonography in discovering and characterizing splenic masses. METHODS: We present the cases of 3 women (aged 72, 61, and 56 years, respectively), all of which had a history of chronic hepatitis C and were subsequently diagnosed with different forms of lymphoma...
July 17, 2018: Ultrasound Quarterly
Mamta K Jain, Mae Thamer, George Therapondos, Mitchell L Shiffman, Onkar Kshirsagar, Christopher Clark, Robert J Wong
BACKGROUND: Direct-acting antivirals (DAA) for hepatitis C virus (HCV) became available in 2014, but the role of mental health or substance use disorders (MH/SUD) on access to treatment is unknown. OBJECTIVE: To examine extent and predictors of HCV treatment in the pre-DAA and post-DAA periods in 4 large, diverse health care settings in the United States (US). METHODS: Retrospective analysis of 29,544 adults with chronic HCV who did or did not receive treatment from 1/1/11-2/28/17...
July 17, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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
Miranda S Moore, Angelica Bocour, Olivia C Tran, Baozhen Qiao, Maria J Schymura, Fabienne Laraque, Ann Winters
Background: Hepatocellular carcinoma (HCC) is a complication of chronic hepatitis B and C virus (HBV and HCV) infection. New York City (NYC) has a high prevalence of HBV and HCV, and infected persons likely face increased mortality from HCC and other causes. We describe the mortality profile of NYC residents with HBV or HCV, emphasizing the contributions of HCC and HIV coinfection. Methods:  Two existing data sets were combined to examine all individuals diagnosed with HBV or HCV in NYC first reported to the Health Department during 2001-2012 and their HCC, HIV, and vital status...
July 2018: Open Forum Infectious Diseases
Zobair M Younossi
Despite highly effective and well-tolerated regimens for treating hepatitis C virus (HCV), patients face barriers in accessing treatment. In addition to suboptimal HCV screening programs and lack of effective linkage-to-care, other barriers include strict requirements from some payers to cover treatment. This study reports insurance status and Hispanic ethnicity as predictors of not receiving treatment. These barriers occur despite the fact that HCV is the most common indication for liver transplantation and cause of hepatocellular carcinoma in the U...
July 18, 2018: American Journal of Gastroenterology
Mona Nili, Lucy Luo, Xue Feng, Jongwha Chang, Xi Tan
BACKGROUND: The study objective was to identify potential sociodemographic disparities in hepatitis C virus (HCV) infection screening among Baby Boomers in the United States. METHODS: We analyzed cross-sectional data from the 2013-2016 National Health Interview Survey. The outcome was whether a person had an HCV infection screening (yes/no). Key independent variables were race/ethnicity, geographic region, poverty level, education level, and health insurance status...
July 13, 2018: American Journal of Infection Control
Kei Morio, Michio Imamura, Yoshiiku Kawakami, Yuki Nakamura, Masahiro Hatooka, Reona Morio, Hatsue Fujino, Takashi Nakahara, Eisuke Murakami, Tomokazu Kawaoka, Masataka Tsuge, Akira Hiramatsu, Hiroshi Aikata, C Nelson Hayes, Daiki Miki, Hidenori Ochi, Yoshio Katamura, Keiko Arataki, Takashi Moriya, Hiroyuki Ito, Keiji Tsuji, Hiroshi Kohno, Koji Waki, Toru Tamura, Toshio Nakamura, Kazuaki Chayama
BACKGROUND: Sustained virological response (SVR) rates for treatment of chronic hepatitis C virus (HCV) infected patients have drastically improved with the use of direct-acting antiviral (DAA) therapies; however, a small minority of patients still fails to eradicate the virus. We analyzed factors associated with SVR in DAA therapy and the effect of age and liver fibrosis on treatment response. METHODS: 918 patients with chronic HCV infection were treated with 24 weeks of daclatasvir plus asunaprevir (DCV/ASV) or 12 weeks of sofosbuvir plus ledipasvir (SOF/LDV), ombitasvir, paritaprevir plus ritonavir (OMB/PTV/r) or sofosbuvir plus RBV (SOF/RBV)...
July 17, 2018: Journal of Medical Virology
Duan Li, Liwei Guo, Baoguo Deng, Min Li, Tingting Yang, Fan Yang, Zhijun Yang
Sterol regulatory element binding protein‑1c (SREBP‑1c), which serves an essential role in the process of fat synthesis, is a key adjustment factor that regulates the dynamic balance of lipid metabolism. SREBP‑1c activates the transcription of multiple genes encoding for enzymes involved in the synthesis of triglycerides (TG) and fatty acids (FA) and accelerates lipid synthesis. Previous analysis indicated that long non‑coding RNA HCV regulated 1 (lncHR1) participates in lipid metabolism in vivo and regulates the level of SREBP‑1c protein...
July 16, 2018: Molecular Medicine Reports
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