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Hepatitis C therapy

Young-A Heo, Emma D Deeks
A fixed-dose combination of the hepatitis C virus (HCV) NS5B polymerase inhibitor sofosbuvir, the HCV NS5A inhibitor velpatasvir and the HCV NS3/4A protease inhibitor voxilaprevir (sofosbuvir/velpatasvir/voxilaprevir; Vosevi® ) is approved in the EU for the treatment of chronic HCV genotype 1, 2, 3, 4, 5 or 6 infection in adults. In the phase III POLARIS trials, in patients who had HCV genotype 1-6 infection with or without compensated cirrhosis, overall rates of sustained virological response at 12 weeks post-treatment (SVR12 ) with sofosbuvir/velpatasvir/voxilaprevir were high after 8 weeks of treatment in direct-acting antiviral (DAA)-naïve patients and 12 weeks of treatment in DAA-experienced patients...
March 15, 2018: Drugs
Alexandre Karras
Cryoglobulins are immunoglobulins that undergo reversible precipitation at low temperatures. They can induce systemic vasculitis, characterized by purpuric cutaneous lesions, arthritis, peripheral neuropathy, hypocomplementemia and glomerular disease. Renal pathology reveals membranoproliferative glomerulonephritis, with particularly intense mesangial cell proliferation and infiltration by macrophages, associated with intracapillary thrombi. This renal disease presents as a nephritic syndrome, with heavy proteinuria, haematuria severe hypertension and rapidly progressive kidney failure that can lead to end-stage renal disease...
March 12, 2018: Néphrologie & Thérapeutique
Lin Cao, Jizheng Chen, Yaxin Wang, Yuting Yang, Jie Qing, Zihe Rao, Xinwen Chen, Zhiyong Lou
Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. Although several HCV protease/polymerase inhibitors were recently approved by U.S. FDA, the combination of antivirals targeting multiple processes of HCV lifecycle would optimize anti-HCV therapy and against potential drug-resistance. Viral entry is an essential target step for antiviral development, but FDA-approved HCV entry inhibitor remains exclusive. Here we identify serotonin 2A receptor (5-HT2A R) is a HCV entry factor amendable to therapeutic intervention by a chemical biology strategy...
March 14, 2018: Protein & Cell
Bangari Haldipur, Prudhvi Lal Bhukya, Vidya Arankalle, Kavita Lole
Molecular mechanisms of liver pathology and clinical disease in HEV infection remain unclear. MicroRNAs are known to modulate viral pathogenesis either by directly altering viral gene expression or by enhancing cellular antiviral responses. Given the importance of microRNA-122 (miR-122) in liver pathobiology, we investigated possible role of miR-122 in HEV infection. In silico predictions using genotype 1, 2, 3 and 4 HEV sequences showed that majority of genomes (203/222) harbor at least one miR-122/miR-122* target site...
March 14, 2018: Journal of Virology
Sofia R Bartlett, Penny Fox, Harris Cabatingan, Anissa Jaros, Carla Gorton, Rhondda Lewis, Eugene Priscott, Gregory J Dore, Darren B Russell
Micro-elimination of hepatitis C virus (HCV) infection through rapid uptake of government-funded direct-acting antiviral (DAA) therapy within an Australian prison setting is demonstrated. During a 22 month period, 119 patients initiated treatment for chronic HCV infection, with HCV in-prison viremic prevalence declining from 12% to 1%.
March 12, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Ossama A Ahmed, Hany H Kaisar, Rehab Badawi, Nehad Hawash, Hossam Samir, Sherif St Shabana, Mohamed Hassan A Fouad, Fatma H Rizk, Samy A Khodeir, Sherief Abd-Elsalam
Background and aims: Treatment of hepatitis C virus (HCV) infection has significantly changed during the last few years. The combination of ledipasvir and sofosbuvir has been shown to treat high proportions of patients with HCV genotype 1 with remarkable tolerability. The aim of the work was to assess the efficacy and safety of sofosbuvir plus ledipasvir in treating treatment-naïve Egyptian patients with genotype 4 HCV infection. Patients and methods: In this open-label randomized study, 200 treatment-naive patients who were HCV antibody positive and HCV RNA positive by polymerase chain reaction, aged >18 years, were enrolled...
2018: Infection and Drug Resistance
Aditya Simha, Camille Maria Webb, Ramakrishna Prasad, N Randall Kolb, Peter J Veldkamp
BACKGROUND AND OBJECTIVE: To determine whether family medicine program directors (PDs) experienced moral distress due to obstacles to Hepatitis C virus (HCV) treatment, and to explore whether they found those obstacles to be unethical. DESIGN: An omnibus survey by the Council of Academic Family Medicine's Educational Research Alliance was administered to 452 and completed by 273 US-based PDs. The survey gauged attitudes and opinions regarding ethical dilemmas in patient access to HCV treatment...
March 2018: Journal of the American Board of Family Medicine: JABFM
Julia L Marcus, Leo B Hurley, Scott Chamberland, Jamila H Champsi, Laura C Gittleman, Daniel G Korn, Jennifer B Lai, Jennifer O Lam, Mary Patricia Pauly, Charles P Quesenberry, Joanna Ready, Varun Saxena, Suk Seo, David J Witt, Michael J Silverberg
BACKGROUND & AIMS: Treatment with the combination of ledipasvir and sofosbuvir for 12 weeks has been approved by the Food and Drug Administration for patients with genotype 1 hepatitis C virus (HCV) infection; some patients can be treated with an 8-week course. Guidelines recommend a 12-week treatment course for black patients, but studies have not compared the effectiveness of 8 vs 12 weeks in black patients who are otherwise eligible for an 8-week treatment regimen. METHODS: We conducted an observational study of Kaiser Permanente Northern California members with HCV genotype 1 infection who were eligible for 8 weeks of treatment with ledipasvir and sofosbuvir (treatment-naïve, no cirrhosis, no HIV infection, level of HCV RNA <6 million IU/mL) and were treated for 8 or 12 weeks from October 2014 through December 2016...
March 10, 2018: Clinical Gastroenterology and Hepatology
O El-Sherif, Z G Jiang, E B Tapper, K C Huang, A Zhong, A Osinusi, M Charlton, M Manns, N H Afdhal, K Mukamal, J McHutchison, D M Brainard, N Terrault, M P Curry
BACKGROUND & AIMS: Treatment with direct-acting antiviral (DAA) agents can reduce model for end-stage liver disease and Child-Pugh-Turcotte (CPT) scores in patients with decompensated cirrhosis caused by hepatitis C virus (HCV). However, many of these patients still die or require liver transplantation. We collected data on baseline features of patients and aimed to develop a scoring system to predict response to DAA therapy. METHODS: We performed a retrospective analysis of data from 4 trials of the effects of sofosbuvir-based therapy in patients with HCV-associated decompensated cirrhosis (502 of CPT class B and 120 of CPT class C)...
March 10, 2018: Gastroenterology
Narayan Ramamurthy, Emanuele Marchi, M Azim Ansari, Vincent Pedergnana, Angela Mclean, Emma Hudson, Rory Bowden, Chris C A Spencer, Ellie Barnes, Paul Klenerman
New directly acting antivirals (DAAs) provide very high cure rates in most patients infected by hepatitis C virus (HCV). However, some patient groups have been relatively harder to treat including those with cirrhosis or infected with HCV genotype 3. In the recent BOSON trial, genotype 3, cirrhotic patients receiving a 16 week course of sofosbuvir and ribavirin had a sustained virologic response rate (SVR) of around 50%. In cirrhotic patients, IFNL4 CC genotype was significantly associated with SVR. This genotype was also associated with a lower interferon-stimulated gene (ISG) signature in peripheral blood and in liver at baseline...
March 13, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Francois M J Lamoury, Sahar Bajis, Behzad Hajarizadeh, Alison D Marshall, Marianne Martinello, Elena Ivanova, Beth Catlett, Yasmin Mowat, Philippa Marks, Janaki Amin, Julie Smith, Nadine Ezard, Victoria Cock, Jeremy Hayllar, David Persing, Marika Kleman, Philip Cunningham, Gregory J Dore, Tanya L Applegate, Jason Grebely
Point-of-care hepatitis C virus (HCV) RNA testing is advantageous enabling diagnosis of active infection in a single visit. This study evaluated the sensitivity and specificity of the Xpert® HCV Viral Load Fingerstick assay (Xpert HCV VL FS) for HCV RNA detection (finger-stick) and the Xpert® HCV Viral Load assay (plasma) compared with the Abbott RealTime HCV Viral Load assay by venepuncture. Plasma and finger-stick capillary whole-blood samples were collected from participants in an observational cohort in Australia...
March 9, 2018: Journal of Infectious Diseases
Hiroyuki Motoyama, Akihiro Tamori, Shoji Kubo, Sawako Uchida-Kobayashi, Shigekazu Takemura, Shogo Tanaka, Satoko Ohfuji, Yuga Teranishi, Ritsuzo Kozuka, Etsushi Kawamura, Atsushi Hagihara, Hiroyasu Morikawa, Masaru Enomoto, Yoshiki Murakami, Norifumi Kawada
BACKGROUND: Hepatocellular carcinoma (HCC) develops in some patients who achieve sustained virological response (SVR) against hepatitis C virus (HCV) infection via anti-HCV therapy. To examine the pathogenesis of HCC development after HCV eradication, histopathological changes and clinical markers were evaluated in SVR patients. METHODS: Of 654 SVR patients treated with interferon (IFN)-based therapies, 34 patients who had undergone liver biopsy before initiating IFN therapy and after SVR achievement were enrolled: 11 patients with HCC and 23 patients without HCC (male/female, 9/2 and 8/15, respectively: age, 58 ± 5 and 54 ± 11 years, respectively)...
2018: PloS One
Abdel-Rahman N Zekri, Enas Reda El-Sisi, Amira Salah El-Din Youssef, Mahmoud M Kamel, Auhood Nassar, Ola Sayed Ahmed, Mohamed El Kassas, Ahmed Barakat Barakat, Alaa Ismail Abd El-Motaleb, Abeer A Bahnassy
AIM: Molecular characterization of the CD133+ stem cells associated with hepatocarinogensis through identifying the expression patterns of specific microRNAs (miRNAs). METHODS: We investigated the expression pattern of 13 miRNAs in purified CD133+ cells separated from the peripheral blood of healthy volunteers, chronic hepatitis C (CHC), liver cirrhosis (LC) and hepatocellular carcinoma (HCC) patients a long with bone marrow samples from the healthy volunteers and the LC patients using custom miScript miRNA PCR array...
2018: PloS One
Francis D Gratte, Sara Pasic, John K Olynyk, George C T Yeoh, David Tosh, Deirdre R Coombe, Janina E E Tirnitz-Parker
The rising prevalence of chronic liver disease, coupled with a permanent shortage of organs for liver transplantation, has sparked enormous interest in alternative treatment strategies. Previous protocols to generate hepatocyte-like cells (HLCs) via pancreas-to-liver transdifferentiation have utilised fetal bovine serum, introducing unknown variables and severely limiting study reproducibility. Therefore, the main goal of this study was to develop a protocol for transdifferentiation of pancreatic progenitor cells to HLCs in a chemically defined, serum-free culture medium...
March 12, 2018: Scientific Reports
J Y Eng, S Y Soon, H Y Winnie Ling
Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare variant of hepatocellular carcinoma. It is commonly reported in the younger population with no underlying chronic liver disease and free of viral Hepatitis B and C. Local recurrence and distant metastasis are common despite better prognosis compared to conventional hepatocellular carcinoma. Complete surgical resection is associated with higher median survival and is the mainstay treatment option for localized FL-HCC. Multi-modality therapies such as TACE can be used to downstage upfront unresectable FL-HCC...
February 2018: Medical Journal of Malaysia
Daniel Enosi Tuipulotu, Natalie E Netzler, Jennifer H Lun, Jason M Mackenzie, Peter A White
Norovirus infections are a significant health and economic burden globally, accounting for hundreds of millions of cases of acute gastroenteritis every year. In the absence of an approved norovirus vaccine, there is an urgent need to develop antivirals to treat chronic infections, and provide prophylactic therapy to limit viral spread during epidemics and pandemics. Toll-like receptor (TLR) agonists have been explored widely for their antiviral potential and several are progressing through clinical trials for the treatment of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and as adjuvants for norovirus virus-like particle (VLP) vaccines...
March 12, 2018: Antimicrobial Agents and Chemotherapy
Kelly H Schlendorf, Sandip Zalawadiya, Ashish S Shah, Mark Wigger, Chan Y Chung, Sarah Smith, Matthew Danter, Chun W Choi, Mary E Keebler, D Marshall Brinkley, Suzanne Brown Sacks, Henry Ooi, Roman Perri, Joseph A Awad, Samuel Lewis, Rachel Hayes, Heather O'Dell, Callie Darragh, Alicia Carver, Cori Edmonds, Shelley Ruzevich-Scholl, JoAnn Lindenfeld
BACKGROUND: Given the shortage of suitable donor hearts for cardiac transplantation, and the favorable safety and efficacy of current agents used to treat hepatitis C virus (HCV), our institution recently piloted transplantation of select patients using HCV-positive donors. METHODS: Between September 2016 and March 2017, 12 HCV-naive patients and 1 patient with a history of treated HCV underwent heart transplantation (HT) using hearts from HCV-positive donors after informed consent...
January 31, 2018: Journal of Heart and Lung Transplantation
Wolfgang Miehsler, Clemens Dejaco, Hans-Peter Gröchenig, Harry Fuchssteiner, Christoph Högenauer, Lili Kazemi-Shirazi, Harald Maier, Andreas Mayer, Alexander Moschen, Walter Reinisch, Wolfgang Petritsch, Reingard Platzer, Pius Steiner, Herbert Tilg, Harald Vogelsang, Heimo Wenzl, Gottfried Novacek
Anti-TNFα-antibodies have revolutionized the therapy of inflammatory bowel diseases and other immune-mediated inflammatory diseases. Due to the increasing application of these substances, the Working Group of Inflammatory Bowel Diseases of the Austrian Association of Gastroenterology and Hepatology intended to update their consensus report on the safe use of Infliximab (published in 2010) and to enlarge its scope to cover all anti-TNFα-antibodies. The present consensus report summarizes the current evidence on the safe use of anti-TNFα-antibodies and covers the following topics: general risk of infection, bacterial infections (i...
March 2018: Zeitschrift Für Gastroenterologie
Ghaly M F, Fadia M Attia, Rania M Saleh, Heba M, Maha Anani
IL-22 plays a vital role in improving hepatic damage by targeting hepatocytes that express high levels of IL-22 receptor1. IP-10 is a chemokine that recruit mononuclear cells to liver parenchyma and improves the host immune response against hepatitis C virus. The study targeted 27 patients with chronic HCV who received pegylated Interferon and Ribavirin. IL-22 and IP-10 serum levels were measured by Elisa. The level of the serum IL-22 is higher in HCV patients groups receiving the antiviral treatment compared to control group and its levels significantly increased with response to treatment...
June 2017: Egyptian Journal of Immunology
Victoria P Strouvelle, Dominique L Braun, Valentina Vongrad, Alexandra U Scherrer, Yik Lim Kok, Roger D Kouyos, Marcel Stöckle, Andri Rauch, Katharine Darling, Matthias Hoffmann, Karin J Metzner, Huldrych F Günthard
Pegylated interferon-alpha (pIFN-α) is suggested to lower HIV-1 DNA load in antiretroviral therapy (ART) treated patients. We studied the kinetics of total HIV-1 DNA levels in 40 HIV-1/hepatitis C (HCV) coinfected patients, treated with pIFN-α for HCV and categorized into three groups according to start of ART: Chronic HIV-1 infection (n=22), acute HIV-1 infection (n=8), no-ART (n=10). Total HIV-1 DNA levels were quantified in 247 PBMC samples and remained stable before, during, and after pIFN-α treatment in all three groups...
March 8, 2018: Journal of Infectious Diseases
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