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hepatitis b phases

Xiao Sun, Xiao-Bin Zhuo, Yi-Ping Hu, Xuan Zheng, Qing-Jie Zhao
Hepatocellular carcinoma (HCC) is among the most common lethal cancers of the digestive system with poor prognosis rates and ineffective therapeutic options. Matrine, a traditional Chinese medicine found in the roots of sophora species, has been used in the clinical treatment of liver fibrosis, chronic hepatitis B and other diseases. We have synthesized a matrine derivatives named WM622 (C26H35ON3S2) with a significant inhibitory effect on transplanted tumors in vivo. The half inhibitory concentration (IC50) of WM622 is 34 µM, which is much lower than matrine...
March 12, 2018: Molecular and Cellular Biochemistry
Mai Hashimoto, Kazuaki Taguchi, Takako Ishiguro, Satoru Kohgo, Shuhei Imoto, Keishi Yamasaki, Hiroaki Mitsuya, Masaki Otagiri
OBJECTIVES: 4'-cyano-2'-deoxyguanosine (CdG), a novel nucleoside analogue, has a high degree of antiviral activity against the chronic hepatitis B virus (HBV). The objective of this study was to develop an analytical method for quantitatively determining CdG levels in biological samples by liquid chromatography-mass spectrometry (LC/MS) and to investigate the pharmacokinetic properties of CdG in rats after intravenous and oral administration. METHODS: An analytical method using a UPLC system interfaced with a TOF-MS system was developed and validated...
March 12, 2018: Journal of Pharmacy and Pharmacology
Erik Mogalian, Diana M Brainard, Anu Osinusi, Lisa Moorehead, Bernard Murray, Kah Hiing John Ling, Robert Perry, Craig Curtis, Eric Lawitz, Kenneth Lasseter, Thomas Marbury, Anita Mathias
BACKGROUND: The pharmacokinetics and safety of velpatasvir, a potent pangenotypic hepatitis C virus NS5A inhibitor, were evaluated in two hepatic impairment studies: a phase I study in hepatitis C virus-uninfected subjects and a phase III study (ASTRAL-4) in hepatitis C virus-infected patients. METHODS: In the phase I study, subjects with moderate or severe hepatic impairment (Child-Pugh-Turcotte Class B or C), and demographically matched subjects with normal hepatic function received a single dose of velpatasvir 100 mg...
March 8, 2018: Clinical Pharmacokinetics
David R Spigel, Craig Reynolds, David Waterhouse, Edward B Garon, Jason Chandler, Sunil Babu, Paul Thurmes, Alexander Spira, Robert Jotte, Jin Zhu, Wen Hong Lin, George Blumenschein
INTRODUCTION: Crizotinib, an anaplastic lymphoma kinase inhibitor, is a first-line treatment for ALK translocation-positive advanced non-small cell lung cancer (NSCLC); however, patients eventually progress. Immunotherapies, including the programmed death-1 inhibitor nivolumab, have resulted in durable responses and long-term overall survival in patients with NSCLC. We hypothesized that combining targeted therapy with immunotherapy could result in more patients with responses and/or more durable responses...
March 5, 2018: Journal of Thoracic Oncology
Jesus Vera-Aguilera, Agop Y Bedikian, Roland L Bassett, Wen-Jen Hwu, Kevin B Kim, Yong Qin, Suzanne Cain, Edwina W Washington, Michael A Davies, Sunil M Patel, Jade Homsi, Nicholas E Papadopoulos, Patrick Hwu, Sapna P Patel
OBJECTIVES: Hepatic arterial infusion (HAI) of cytotoxic chemotherapy is a strategy to deliver high dose of anticancer therapy to liver metastases that derive their blood supply from the hepatic artery. Metastatic melanoma (MM) has a high incidence of liver metastases, with uveal subtype in particular exhibiting a predilection for liver dissemination. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) has demonstrated efficacy in MM and first-pass hepatic metabolism. Therefore, we hypothesized that HAI of nab-paclitaxel would deliver an effective dose of drug to the end organ of interest, with minimal systemic exposure...
March 5, 2018: American Journal of Clinical Oncology
Zobair M Younossi, Maria Stepanova, Harry L A Janssen, Kosh Agarwal, Mindie H Nguyen, Ed Gane, Naoky Tsai, Issah Younossi, Andrei Racila
BACKGROUND AND AIM: Chronic infection with hepatitis B virus (HBV) causes liver disease and cirrhosis. It is not clear how treatment of chronic HBV infection affects patient-reported outcomes (PROs). We aimed to assess changes in PROs in patients treated for chronic HBV infection. METHODS: We collected and analyzed PRO data from 242 patients with chronic HBV infection (without advanced fibrosis or cirrhosis) enrolled in 2 international phase 2 blinded controlled clinical trials from 2015 through 2017...
March 2, 2018: Clinical Gastroenterology and Hepatology
Jakob Weiss, Mike Notohamiprodjo, Jana Taron, Petros Martirosian, Dominik Nickel, Fabian Bamberg, Konstantin Nikolaou, Ahmed E Othman
PURPOSE: The aim of this study was to evaluate the feasibility of a prototype volume-interpolated breath-hold examination (VIBE) sequence using compressed sensing (VIBECS) for rapid multiphase arterial magnetic resonance imaging (MRI) at different temporal resolution during free-breathing in comparison with a conventional breath-hold approach (VIBESTD). MATERIAL AND METHODS: A total of 40 patients with liver malignancies were prospectively included in this study and underwent contrast-enhanced liver MRI at 1...
February 28, 2018: Investigative Radiology
John F Marcinak, Melvin S Munsaka, Paul B Watkins, Takashi Ohira, Neila Smith
INTRODUCTION: Fasiglifam (TAK-875) is a G protein-coupled receptor 40 agonist that was being investigated for treatment of type 2 diabetes mellitus (T2DM). A development program was terminated late in phase III clinical trials due to liver safety concerns. METHODS: The liver safety of fasiglifam was assessed from data based on six phase II and nine phase III double-blind studies and two open-label studies with emphasis on pooled data from 15 double-blind studies from both global and Japanese development programs...
February 28, 2018: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
Na Yang, Jin Feng, Zhuo R Li, Kai H Ming, Xiu X Lei, Bang L Xu
BACKGROUND: Chronic hepatitis B patients carry a high risk of developing hepatocellular carcinoma (HCC). α-Fetoprotein (AFP) is one of the most commonly used and reliable biomarkers for HCC. However, the AFP level during different phases of CHB is not well understood. We aimed to identify the AFP levels during the different infection phases of CHB patient and explore which phase is at high risk of developing HCC. METHODS: Three hundred and fifty-five CHB patients were divided into four groups: a...
January 1, 2018: Clinical Laboratory
Weiguo Zhang, Xiao Wang, Youhan Miao, Chunhong Hu, Weifeng Zhao
PURPOSES: To determine if liver-to-portal vein contrast ratio (LPC) correlates with liver function in patients with hepatitis B virus (HBV)-related cirrhosis on gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA)-enhanced MR imaging. METHODS: A total of 92 patients with normal (n = 20) or HBV-related cirrhotic livers graded by Child-Pugh class A (n = 50), B (n = 17) or C (n = 5) who underwent Gd-EOB-DTPA-enhanced 3Tesla MR imaging were retrospectively reviewed...
February 23, 2018: Abdominal Radiology
Sree Harsha Tirumani, Jyothi P Jagannathan, Marta Braschi-Amirfarzan, Lei Qin, Patricia Balthazar, Nikhil H Ramaiya, Atul B Shinagare
OBJECTIVE: To compare hepatocellular phase imaging after intravenous gadoxetate disodium with other MRI pulse sequences and with extracellular agent for assessing hepatic metastases from gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). MATERIALS AND METHODS: In this IRB-approved, HIPAA-compliant retrospective study, we included 30 patients (15 women, mean age: 58 years, range 44-77 years) with GEP-NEN metastatic to the liver, who underwent MRI with gadoxetate disodium...
February 22, 2018: Abdominal Radiology
Conar R O'Neil, Stephen E Congly, M Sarah Rose, Samuel S Lee, Meredith A Borman, Carmen L Charlton, Carla Osiowy, Mark G Swain, Kelly W Burak, Carla S Coffin
INTRODUCTION: Quantitative hepatitis B surface antigen (qHBsAg) combined with HBV DNA may be useful for predicting chronic hepatitis B (CHB) activity and nucleoside analogue (NA) response. MATERIAL AND METHODS: In this retrospective cohort study we evaluated qHBsAg levels according to CHB disease phase and among patients on treatment. Random effect logistic regression analysis was used to analyze qHBsAg change with time in the NA-treated cohort. RESULTS: 545 CHB carriers [56% M, median age 48 y (IQR 38-59), 73% Asian] had qHBsAg testing...
March 1, 2018: Annals of Hepatology
Anthony B El-Khoueiry, John Sarantopoulos, Cindy L O'Bryant, Kristen K Ciombor, Huiping Xu, Melissa O'Gorman, Jayeta Chakrabarti, Tiziana Usari, Bassel F El-Rayes
PURPOSE: This phase 1 study evaluated the effect of hepatic impairment on pharmacokinetics and safety of crizotinib in patients with advanced cancer. METHODS: Patients were dosed according to hepatic function classified by modified National Cancer Institute Organ Dysfunction Working Group criteria and group assignment [normal (A1 and A2), mild (B), moderate (C1 and C2), or severe (D)]. Primary pharmacokinetic endpoints included area under the concentration-time curve as daily exposure (AUCdaily ) and maximum plasma concentration (Cmax ) at steady state...
February 21, 2018: Cancer Chemotherapy and Pharmacology
Fuchen Liu, Zeya Pan, Jinmin Zhang, Junsheng Ni, Chao Wang, Zhenguang Wang, Fangming Gu, Wei Dong, Weiping Zhou, Hui Liu
Aberrant expression of Ras homolog enriched in brain (RHEB) has been observed in a variety of cancer tissues and is closely associated with clinicopathological features. However, the expression profile of RHEB in patients with hepatocellular carcinoma (HCC) and its clinical signature with underlying mechanisms have not been explored thus far. To analyze the association between RHEB expression and clinicopathological features, the RHEB expression levels were determined in the present study using gene microarrays, immunohistochemistry and western blotting in 60 liver cancer tissues and 35 normal liver tissues...
March 2018: Oncology Letters
Stefano Colagrande, Linda Calistri, Giulia Grazzini, Cosimo Nardi, Simone Busoni, Giovanni Morana, Luigi Grazioli
PURPOSE: Our retrospective study sought to describe the spectrum of magnetic resonance imaging (MRI) features of primary hepatic lymphoma (PHL) by analyzing its morphological aspects, signal intensity before and after contrast agent (CA) administration, and diffusion-weighted imaging (DwI) with the apparent diffusion coefficient (ADC) values. METHODS: A retrospective analysis was conducted on 25 patients with pathologically proven PHL who underwent MRI between January 2011 and December 2016...
February 19, 2018: Abdominal Radiology
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
Can Liu, Wennan Wu, Hongyan Shang, Sheng Lin, Zhen Xun, Er Huang, Jinpiao Lin, Bin Yang, Qishui Ou
BACKGROUND: Serum HBV large surface protein (HBV-LP) is an envelope protein that has a close relationship with HBV DNA level. This study is to explore the prediction value of HBV-LP in different phase of HBV infection and during antiviral therapy in chronic hepatitis B (CHB) patients. METHODS: A retrospective study was conducted in 2033 individuals, which included 1677 HBV infected patients in different phases and 356 healthy controls. HBV-LP, HBV serum markers and HBV DNA were detected by ELISA, CMIA and qRT-PCR, respectively...
February 14, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
Hyun S Kim, Walid L Shaib, Chao Zhang, Ganji Purnachandra Nagaraju, Christina Wu, Olatunji B Alese, Zhengjia Chen, Edith Brutcher, Meredith Renfroe, Bassel F El-Rayes
BACKGROUND: Neuroendocrine tumors (NETs) metastasize to the liver. Everolimus and selective internal radioembolization (SIRT) are approved treatments. Pasireotide is a somatostatin analogue with an affinity for somatostatin receptors 1, 2, 3, and 5. Everolimus and pasireotide may potentiate SIRT radiosensitization and inhibit rebound angiogenesis. This study evaluated the safety of pasireotide, everolimus, and SIRT. METHODS: This 3 + 3 phase 1 trial evaluated 3 dose levels of everolimus (2...
February 16, 2018: Cancer
Jacques Cadranel, Alexis B Cortot, Hervé Lena, Bertrand Mennecier, Pascal Do, Eric Dansin, Julien Mazieres, Christos Chouaid, Maurice Perol, Fabrice Barlesi, Gilles Robinet, Sylvie Friard, Luc Thiberville, Clarisse Audigier-Valette, Alain Vergnenegre, Virginie Westeel, Khemaies Slimane, Alexandru Buturuga, Denis Moro-Sibilot, Benjamin Besse
Here we report our experience of ceritinib in crizotinib-pretreated patients with anaplastic lymphoma kinase ( ALK ) positive ( ALK + ) non-small cell lung cancer (NSCLC) in a French temporary authorisation for use (TAU) study. The French TAU study included crizotinib-pretreated patients with advanced ALK + or ROS proto-oncogene 1 positive ( ROS1 + ) tumours. Patients received oral ceritinib (750 mg·day -1 as a starting dose) and best tumour response (as evaluated by the investigator) and safety were reported every 3 months...
January 2018: ERJ Open Research
Iulia A Neagu, Jason Olejarz, Mark Freeman, Daniel I S Rosenbloom, Martin A Nowak, Alison L Hill
Viral infections are one of the major causes of death worldwide, with HIV infection alone resulting in over 1.2 million casualties per year. Antiviral drugs are now being administered for a variety of viral infections, including HIV, hepatitis B and C, and influenza. These therapies target a specific phase of the virus's life cycle, yet their ultimate success depends on a variety of factors, such as adherence to a prescribed regimen and the emergence of viral drug resistance. The epidemiology and evolution of drug resistance have been extensively characterized, and it is generally assumed that drug resistance arises from mutations that alter the virus's susceptibility to the direct action of the drug...
February 2018: PLoS Computational Biology
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