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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
Gurmit Kaur Jagjit Singh, Steve Kaye, James C Abbott, Christoph Boesecke, Juergen Rockstroh, Myra O McClure, Mark Nelson
Background The epidemic of acute HCV infection among HIV-infected men who have sex with men (MSM) is ongoing. Transmission of drug-resistant variants (DRVs) after HCV treatment failure could pose a major threat to the effectiveness of future therapies. We determined the baseline prevalence of pre-existing DRVs in the HCV NS3 protease gene and their effects on the addition of telaprevir (TVR) to standard pegylated interferon and ribavirin (PEG-IFN/RBV) for acute HCV infection in individuals enrolled in a multicentre randomized controlled trial (2013 and 2014)...
March 1, 2018: HIV Clinical Trials
Mario Rizzetto
New therapeutic strategies to treat chronic hepatitis D are directed to deprive the hepatitis D virus (HDV) of functions necessary to complete its life cycle that are provided by the hepatitis B virus (HBV) and by the host. Current options are (1) the block by the synthetic peptide Myrcludex B of HBV surface antigen (HBsAg) entry into cells through the inhibition of the sodium taurocholate cotransporting receptor; (2) the inhibition with lonafarnib of the farnesylation of the large HD antigen, required for virion assembly; (3) the presumed reduction by the nucleic acid polymer REP 2139 of the release of the HBsAg and subviral HBV particles necessary for HD virion morphogenesis...
February 2018: Seminars in Liver Disease
Meng-Lan Wang, Juan Liao, Bing Wei, Dong-Mei Zhang, Ming He, Ming-Chuan Tao, En-Qiang Chen, Hong Tang
AIM: Recent studies revealed that both quantitative hepatitis B surface antigen (qHBsAg) and hepatitis B core-related antigen (qHBcrAg) could serve as a good marker for predicting treatment response and indirectly reflecting intrahepatic cccDNA levels. This study aimed to compare the value of qHBsAg and qHBcrAg in predicting HBeAg seroconversion among patients undergoing PEG-IFN therapy. METHODS: A total of 31 HBeAg-positive patients, who underwent PEG-IFN therapy for 12 months and follow-up for six months were retrospectively included in this study...
February 20, 2018: Infectious Diseases
Yingying Wu, Yongbin Zeng, Wennan Wu, Jinpiao Lin, Qishui Ou
BACKGROUND: Host single nucleotide polymorphisms were associated with antiviral therapy in CHB patients. The CYP27B1 gene, encoding 25(OH)D3 -1α hydroxylase, might activate 25(OH)D3 to 1,25(OH)2 D3 in kidney resulted in influencing the efficacy of interferon (IFN). The aim of the study was to investigate the association between CYP27B1 polymorphisms and the response to IFN in HBeAg-positive patients. METHODS: Eighty-seven HBeAg-positive CHB patients infected with HBV genotype B or C were included in the study...
February 18, 2018: Journal of Clinical Laboratory Analysis
Chao-Wei Hsu, Wei-Wen Su, Chuan-Mo Lee, Cheng-Yuan Peng, Wan-Long Chuang, Jia-Horng Kao, Heng-Cheng Chu, Yi-Hsiang Huang, Rong-Nan Chien, Yun-Fan Liaw
BACKGROUND: Efficacy of sequential therapy with nucleos(t)ide analogues and interferons versus monotherapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) remains unexplored. We aimed to assess efficacy and safety of sequential therapy with adefovir (ADV) or entecavir (ETV) followed by peginterferon (PEG-IFN) alfa-2a in Taiwanese patients with HBeAg-positive. METHODS: This randomized, placebo-controlled, double-blind trial was conducted at nine sites in Taiwan from April 2010 to October 2013...
February 15, 2018: Journal of the Formosan Medical Association, Taiwan Yi Zhi
Dejuan Sun, Lingjuan Zhu, Dahong Yao, Lixia Chen, Leilei Fu, Liang Ouyang
Hepatitis B virus (HBV) infections affect about 240 million patients worldwide and increase the risk of liver cirrhosis and hepatocellular carcinoma. It is estimated that about 686 thousand people died annually of liver damage resulted from HBV infections. At present, two classes of antiviral drugs have been approved by the Food and Drug Administration (FDA) for the treatment of hepatitis B, immunomodulators (interferon [IFN]-a and pegylated-interferon [PEG-IFN]-a) and nucleos(t)ide analogs (lamivudine, telbivudine, adefovir, tenofovir [TDF], and entecavir [ETV])...
February 5, 2018: European Journal of Medicinal Chemistry
Satoru Hagiwara, Naoshi Nishida, Tomohiro Watanabe, Hiroshi Ida, Toshiharu Sakurai, Kazuomi Ueshima, Masahiro Takita, Yoriaki Komeda, Norihiro Nishijima, Yukio Osaki, Masatoshi Kudo
BACKGROUND: Although the efficacy of combination therapy with lamivudine or tenofovir and pegylated-interferon (Peg-IFN) has been reported in patients with chronic hepatitis B (CHB), the long-term effect of the combination based on the observation of clinical course remains to be clarified. We previously reported the efficacy of combination therapy with entecavir (ETV) and Peg-IFN. Here, we investigated the long-term effect of this combination in patients with CHB. METHODS: We administered both ETV and Peg-IFN α-2a or -2b simultaneously to 26 patients with hepatitis B virus genotype C infection...
February 13, 2018: Antiviral Therapy
Mauro Viganò, Glenda Grossi, Alessandro Loglio, Pietro Lampertico
The treatment of chronic hepatitis B (CHB) patients is based on monotherapy with pegylated-interferon (Peg-IFN) or with one of the three most potent nucleot(s)ide analogues (NUCs) with the best resistance profiles, i.e. entecavir (ETV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). Long-term NUCs treatment can achieve virological suppression in almost all patients. However, this requires lifelong therapy, is costly and the rate of hepatitis B surface antigen (HBsAg) seroclearance is low...
February 2018: Liver International: Official Journal of the International Association for the Study of the Liver
Dan Yan Zhu, Xiao Zhao Deng, Yu Meng Zhu, Guo Tao Li, Guo Qiang Zhang, Ling Ju Wang, Jing Hai Zhang, Wen Xiao, Zhen Xian Zhou, Wei Liang Ding
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. The outcomes of both spontaneous HCV clearance and response to therapy depend on both viral and host factors. To investigate the influence of polymorphisms of IL-28B rs12979860 and TBX21 rs17250932, rs4794067 as well as viral factors (HCV genotype, F protein) on the outcome of HCV infection, we genotyped 565 patients with chronic HCV infection, 191 patients spontaneously resolved from HCV infection, 359 healthy controls and 383 treatment-naïve CHC patients with pegylated interferon-α and ribavirin (PEG IFN-α/RBV)...
February 5, 2018: Archives of Virology
Lucio Boglione, Giuseppe Cariti, Valeria Ghisetti, Elisa Burdino, Giovanni Di Perri
An alternative approach in the treatment of chronic hepatitis B (CHB) with pegylated (PEG)-interferon (IFN) is the prolonged course to 96 weeks of therapy, with higher sustained response (SR) than patients treated for 48 weeks. This result was confirmed in patients with CHB and D genotype, while no data are currently available about the prolonged course of PEG-IFN in E genotype. This retrospective analysis reported the role of different treatment duration of PEG-IFN on the SR in patients affected by CHB and E genotype...
January 31, 2018: Journal of Medical Virology
Manu Asthana, Sushil Kumar Sahu, Amit Kumar, Suchitra Mohanty, Sudipta Chakrabarti, Piyanki Das, Nabanita Roy Chattopadhya, Koustav Chatterjee, Shivaram Prasad Singh, Shanmugam Rajasubramaniam, Tathagata Choudhuri
Interleukin-28B (IL28B) locus on a human chromosomal region 19q13 is responsible for immune protection against viruses. IL28B in hepatitis C virus (HCV) infection determines the fate of infection towards causing spontaneous clearance or chronic liver infection. Choice of treatment in chronic hepatitis C infection includes use of direct acting antivirals, pegylated-interferon (PEG-IFN) or ribavirin (RBV) therapy. Interferon free regimens are also suggested to be useful in drug resistant patients. Genome-wide association studies (GWAS), comprehensive meta-analysis and independent case-control studies in different ethnic populations have demonstrated association between certain Il-28B polymorphisms and its effect on the response to PEG-IFN-RBV therapy in HCV patients...
January 28, 2018: Current Drug Metabolism
Michael B Atkins, F Stephen Hodi, John A Thompson, David McDermott, Wen-Jen Hwu, Donald P Lawrence, Nancy A Dawson, Deborah Jean Lee Wong, Shailender Bhatia, Marihella James, Lokesh Jain, Seth Robey, Xinxin Shu, Blanca Homet Moreno, Rodolfo F Perini, Toni K Choueiri, Antoni Ribas
PURPOSE: Pembrolizumab, ipilimumab, and pegylated interferon alfa-2b (PEG-IFN) monotherapy are active against melanoma and renal cell carcinoma (RCC). We explored the safety and preliminary antitumor activity of pembrolizumab combined with either ipilimumab or PEG-IFN in patients with advanced melanoma or RCC. EXPERIMENTAL DESIGN: The phase 1b KEYNOTE-029 study (, NCT02089685) included independent pembrolizumab plus reduced-dose ipilimumab and pembrolizumab plus PEG-IFN cohorts...
January 22, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Mohamed El Kassas, Dalia Omran, Kadry Elsaeed, Mohamed Alboraie, Wafaa Elakel, Adel El Tahan, Yasmeen Abd El Latif, Mohamed Mahmoud Nabeel, Mohamed Korany, Sameera Ezzat, Magdy El-Serafy, Yehia ElShazly, Wahid Doss, Gamal Esmat
The aim of this study was to retrospectively analyze the outcome of an unscheduled change in national Egyptian policies for the treatment of hepatitis C virus (HCV), which was transpired as a result of a reduction in interferon supplies, and to manage patients who already started interferon-based therapy. After completing a priming 4-weeks course of sofosbuvir/pegylated interferon/ribavirin (SOF/PEG IFN/RBV), a 12-weeks course of sofosbuvir/daclatasvir (SOF/DCV) combination was initiated. We evaluated the sustained virologic response at 12 weeks posttreatment (SVR12) for 2 groups of patients; Group 1, which included patients who had the previous regimen with IFN priming, and group 2, which included the first consecutive group of patients who received SOF/DCV for 12 weeks from the start without IFN priming...
January 22, 2018: Journal of Interferon & Cytokine Research
Zaid Mutahar Mohammed Alezzi, Ayman Yosry Abd El Rehim, Waleed Fouad Fathallah, Mansour Ali Alamrani, Fouad Hezam Othman
Hepatitis C virus (HCV) infection is increasingly seen as a major public health problem, threat, and concern worldwide. In Yemen about 1.7% of the population is infected with chronic hepatitis C. This study aimed to detect the predictors for response to pegylated interferon and ribavirin (Peg-IFN/RBV) in chronic HCV Yemeni patients. The study was conducted on 100 patients with chronic HCV who received Peg-IFN/RBV in the 48th Military Hospital in Sana'a Yemen, from 2011 to 2013. All patients were subjected to complete history taking, thorough clinical examinations, routine laboratory investigation, and abdominal ultrasonography...
January 2018: Journal of Interferon & Cytokine Research
X D Luo, X P Chen, X F Chen
Objective: To investigate the optimal treatment regimen for patients with HBeAg-positive chronic hepatitis B (CHB) after suboptimal response to 24 weeks of pegylated interferon (Peg-IFN) α-2a. Methods: A total of 188 patients with HBeAg-positive CHB who had suboptimal response to 24 weeks of Peg-IFN α-2a were randomly divided into entecavir group (n = 93) and telbivudine group (n = 95). The two groups received entecavir 0.5 mg/d and telbivudine 0.6 g/d, respectively, for 208 weeks. After 208 weeks of treatment, the following indices were assessed: HBeAg clearance rate and seroconversion rate, hepatitis B virus (HBV) DNA clearance rate (HBV DNA < 500 IU/ml), safety, and drug resistance rate...
December 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Terumi Kaishima, Tomoyuki Akita, Masayuki Ohisa, Kazuaki Sakamune, Akemi Kurisu, Aya Sugiyama, Hiroshi Aikata, Kazuaki Cyayama, Junko Tanaka
AIM: We estimated the cost-effectiveness of direct acting antiviral treatment (DAA) compared to triple therapy (simeprevir, pegylated interferon-α and ribavirin) (scenario-1) and Peg-IFN+RBV(scenario-2) and non-antiviral therapy(scenario-3). METHODS: The Cost-effectiveness was evaluated as incremental cost-effectiveness ratios (ICERs) using direct costs and indirect costs which included loss of wages during the patient's lifetime due to early death caused by viral hepatitis infection...
January 5, 2018: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Ankur Jindal, Ashish Kumar Vyas, Devesh Kumar, Guresh Kumar, Manoj Kumar Sharma, Shiv Kumar Sarin
BACKGROUND: Monotherapy with Peg-IFNα or nucleos(t)ide analogues(NA) currently approved for treating chronic hepatitis B(CHB) have limited efficacy. Studies on combination of Peg-IFN-α/NA have shown conflicting results. We investigated whether sequential adding-on Peg-IFNα to tenofovir enhances serological response rates. METHODS: Treatment naïve, HBeAg-positive CHB patients with moderately elevated ALT(48 to 200IU/mL) were started on tenofovir(300 mg/day) and enrolled at week 12 in 1:1 ratio to either receive Peg-IFNα2b add-on(1...
January 4, 2018: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Lars Peters, Amanda Mocroft, Daniel Grint, Santiago Moreno, Alexandra Calmy, Djordje Jevtovic, Helen Sambatakou, Karine Lacombe, Stephane De Wit, Jürgen Rockstroh, Jelena Smidt, Igor Karpov, Anna Grzeszczuk, Vesnadarjan Haziosmanovic, Magnus Gottfredsson, Roxana Radoi, Elena Kuzovatova, Chloe Orkin, Anna Lisa Ridolfo, Jose Zapirain, Jens Lundgren
BACKGROUND: According to guidelines all HIV/HBV co-infected patients should receive tenofovir-based combination antiretroviral therapy (cART). We aimed to investigate uptake and outcomes of tenofovir-based cART among HIV/HBV patients in the EuroSIDA study. METHODS: All HBsAg+ patients followed up after 1 March 2002 were included. Changes in the proportion taking tenofovir-based cART over time were described. Poisson regression was used to investigate the relationship between tenofovir use and clinical events...
January 5, 2018: Antiviral Therapy
Giuseppe Indolfi, Loreto Hierro, Antal Dezsofi, Jörg Jahnel, Dominique Debray, Nedim Hadzic, Piotr Czubowski, Girish Gupte, Yael Mozer-Glassberg, Wendy van der Woerd, Françoise Smets, Henkjan J Verkade, Björn Fischler
OBJECTIVES: In 2017, the European Medicines Agency and the Food and Drug Administration approved the use of the fixed-dose combination of ledipasvir/sofosbuvir and of the combination of sofosbuvir and ribavirin for treatment of adolescents (12-17 years or weighing >35 kg) with chronic hepatitis C virus (HCV) genotype 1, 4, 5, and 6 and genotype 2 and 3 infections, respectively. Although trials with direct-acting antivirals are ongoing for younger children, the only available treatment in the United States and Europe for those <12 years is still the dual therapy of pegylated interferon and ribavirin...
March 2018: Journal of Pediatric Gastroenterology and Nutrition
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