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https://www.readbyqxmd.com/read/29913090/oral-chemotherapy-for-the-treatment-of-hepatocellular-carcinoma
#1
Shun Yamamoto, Shunsuke Kondo
Many clinical trials have been conducted with chemotherapies in patients with advanced hepatocellular carcinoma (HCC). However, few agents have shown efficacy. It is thought that the efficacy of some agents might have resulted from the heterogeneity of tumors, insufficient dosages due to liver cirrhosis, and post-therapy effects. In recent years, immune checkpoint inhibitors have shown promising clinical activity and safety in patients with advanced HCC. Areas covered: The authors provide an overview of chemotherapies used for the treatment of HCC, including ongoing trials...
June 18, 2018: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29912757/dietary-interventions-in-liver-cirrhosis
#2
Chu Kion Yao, James Fung, Natural Hoi Sing Chu, Victoria Ping Yi Tan
Liver cirrhosis is associated with significant nutritional risks that often result in serious hepatic complications and poor survival rates. Diet is an important but underutilized aspect in the treatment modality of cirrhosis. Therefore, the aims of this review are to ascertain nutritional risks associated with its pathophysiology and to summarize existing evidence that support dietary recommendations for managing this patient population. Alterations in substrate utilization for energy production is a main feature of liver cirrhosis, resulting in increased catabolism of protein stores and a predisposition toward protein-energy malnutrition, even in the early stages of the disease...
June 16, 2018: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/29912756/hyperlipidemia-and-nonalcoholic-steatohepatitis-predispose-to-hepatocellular-carcinoma-development-without-cirrhosis
#3
Jennifer Phan, Vivian Ng, Alan Sheinbaum, Sam French, Gina Choi, Mohamed El Kabany, Francisco Durazo, Sammy Saab, Myron Tong, Ronald Busuttil, Steven-Huy Han
BACKGROUND: Hepatocellular carcinoma (HCC) accounts for 90% of primary hepatic malignancies. With the exception of chronic hepatitis B (CHB), other etiologies of chronic liver disease require progression to cirrhosis before HCC development. Case reports have described HCC in noncirrhotic patients with hepatitis C (HCV) and nonalcoholic fatty liver disease. GOAL: The aim of this study was to determine the prevalence of patients without cirrhosis and CHB who developed HCC among a large cohort of HCC patients and to identify independent variables that are associated with no cirrhosis among patients with HCC...
June 16, 2018: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/29912318/bayesian-inference-for-network-meta-regression-using-multivariate-random-effects-with-applications-to-cholesterol-lowering-drugs
#4
Hao Li, Ming-Hui Chen, Joseph G Ibrahim, Sungduk Kim, Arvind K Shah, Jianxin Lin, Andrew M Tershakovec
Low-density lipoprotein cholesterol (LDL-C) has been identified as a causative factor for atherosclerosis and related coronary heart disease, and as the main target for cholesterol- and lipid-lowering therapy. Statin drugs inhibit cholesterol synthesis in the liver and are typically the first line of therapy to lower elevated levels of LDL-C. On the other hand, a different drug, Ezetimibe, inhibits the absorption of cholesterol by the small intestine and provides a different mechanism of action. Many clinical trials have been carried out on safety and efficacy evaluation of cholesterol lowering drugs...
April 18, 2018: Biostatistics
https://www.readbyqxmd.com/read/29912274/selective-ret-kinase-inhibition-for-patients-with-ret-altered-cancers
#5
V Subbiah, V Velcheti, B B Tuch, K Ebata, N L Busaidy, M E Cabanillas, L J Wirth, S Stock, S Smith, V Lauriault, S Corsi-Travali, D Henry, M Burkard, R Hamor, K Bouhana, S Winski, R D Wallace, D Hartley, S Rhodes, M Reddy, B J Brandhuber, S Andrews, S M Rothenberg, A Drilon
Purpose: Alterations involving the RET kinase are implicated in the pathogenesis of lung, thyroid and other cancers. However, the clinical activity of multikinase inhibitors with anti-RET activity in RET-altered patients appears limited, calling into question the therapeutic potential of targeting RET. LOXO-292 is a selective RET inhibitor designed inhibit diverse RET fusions, activating mutations and acquired resistance mutations. Patients and Methods: Potent anti-RET activity, high selectivity, and central nervous system coverage were confirmed preclinically using a variety of in vitro and in vivo RET-dependent tumor models...
April 18, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29912045/liver-perfusate-natural-killer-cells-from-deceased-brain-donors-and-association-with-acute-cellular-rejection-after-liver-transplantation-a-time-to-rejection-analysis
#6
Duilio Pagano, Ester Badami, Pier Giulio Conaldi, Aurelio Seidita, Fabio Tuzzolino, Marco Barbàra, Fabrizio di Francesco, Alessandro Tropea, Rosa Liotta, Gaia Chiarello, Angelo Luca, Salvatore Gruttadauria
BACKGROUND: The ability to predict which recipients will successfully complete their posttransplant clinical course, is crucial for liver transplant (LT) programs. The assessment of natural killer (NK) cell subset determined by flow cytometry from a monocentric series of consecutive liver perfusates (LPs) could help identify risk factors portending adverse LT outcomes. METHODS: LPs were collected during the back-table surgical time after the procurement procedures for donors after brain death (DBDs)...
June 13, 2018: Transplantation
https://www.readbyqxmd.com/read/29911165/participatory-epidemiology-of-endemic-diseases-in-west-african-cattle-ethnoveterinary-and-bioveterinary-knowledge-in-fulani-disease-control
#7
Ayodele O Majekodunmi, Charles Dongkum, Christopher Idehen, Dachung Tok Langs, Susan C Welburn
Fulani pastoralists in Nigeria lack adequate access to good quality veterinary services and often resort to treating their animals themselves. There are several negative aspects to this, including poor treatment outcomes, misuse of veterinary drugs and subsequent resistance, and further barriers to good relations between pastoralists and veterinary services. A participatory epidemiology survey was undertaken in Fulani communities, to examine their ability to diagnose and treat bovine diseases. Qualitative participatory epidemiology techniques including semi-structured interviews, ranking and participant and non-participant observations were used for data collection...
June 2018: One Health
https://www.readbyqxmd.com/read/29910796/the-complement-system-and-c1q-in-chronic-hepatitis-c-virus-infection-and-mixed-cryoglobulinemia
#8
REVIEW
Ahmed El-Shamy, Andrea D Branch, Thomas D Schiano, Peter D Gorevic
The complement system bridges innate and adaptive immunity against microbial infections, with viral infection being a major trigger. Activation of the classical, alternative, and lectin pathways have been reported in chronic hepatitis C virus (HCV) infection and/or cryoglobulinemia. HCV infection leads to dysregulation of complement-mediated immune responses. Clinical and experimental evidence support involvement of complement in intra- and extrahepatic manifestations of HCV infection, such as liver fibrosis and type II cryoglobulinemia...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29910623/obesity-associated-mir-27a-upregulation-promotes-hepatocellular-carcinoma-metastasis-through-suppressing-sfrp1
#9
Yang Chen, Fan Zhang, Yawei Zhao, Kan He, Xiao Zheng, Yue Pan, Dan Shao, Pei Shang, Yongsheng Yang, Dan Zhang, Yingjun Xie, Xiaoxiao Yao, Li Chen, Jing Li, Xuewen Zhang
Background: Obesity was a recognized risk factor for the development and progression of hepatocellular carcinoma (HCC). However, the effects and mechanisms by which obesity promotes HCC metastasis remain poorly understood. Materials and methods: We cultured adipocyte induced by preadipocyte 3T3-L1 in vitro and established HCC metastasis model in obesity mouse in vivo to mimic the tumor microenvironment in obese status. The mechanisms underlying obesity-associated miR-27a upregulation promoting HCC metastasis were investigated...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29910458/atypical-presentation-of-adrenocortical-insufficiency-with-anorexia-and-jaundice
#10
Xiang-Xing Li, Jie Liu, You-Lian Chen, Guang-Jian Chen, Zhen-Yu Wang, Jun-Jun Zhu, Yun-Wei Guo, Xiu-Qing Wei
BACKGROUND Adrenal insufficiency is mainly due to insufficient adrenal corticosteroid hormones secretion by the adrenal cortex, which leads to clinical manifestations such as weakness, weight loss, hyperpigmentation, hypotension, and vomiting. However, the clinical manifestations of adrenocortical insufficiency may be atypical: anorexia, ascites, impaired liver function, and alacrima have been reported. Jaundice and anorexia presenting together in the same patient as the main symptoms are rare. CASE REPORT We present a rare case of a 65-year-old woman diagnosed as having adrenocortical insufficiency with chief complaints of anorexia and jaundice...
June 18, 2018: American Journal of Case Reports
https://www.readbyqxmd.com/read/29910217/hormone-replacement-therapy-for-hepatopulmonary-syndrome-and-nash-associated-with-hypopituitarism
#11
Nobuyuki Torii, Atsuhiro Ichihara, Yuki Mizuguchi, Yasufumi Seki, Etsuko Hashimoto, Katsutoshi Tokushige
The patient was a 23-year-old man who was diagnosed with severe hypoxemia and liver dysfunction after suffering from sudden difficulty breathing. At 2 years of age, he had been diagnosed with hypopituitarism, and had received hormone-replacement until he was 18 years of age. Echocardiography using micro bubbles and pulmonary scintigraphy indicated intrapulmonary shunt and a liver biopsy showed steatohepatitis. He was diagnosed with hepatopulmonary syndrome associated with nonalcoholic steatohepatitis. Hormone-replacement therapy was re-started...
2018: Internal Medicine
https://www.readbyqxmd.com/read/29910011/misconceptions-preferences-and-barriers-to-alcohol-use-disorder-treatment-in-alcohol-related-cirrhosis
#12
Jessica L Mellinger, G Scott Winder, Melissa DeJonckheere, Robert J Fontana, Michael L Volk, Anna S F Lok, Frederic C Blow
BACKGROUND: While alcohol cessation improves mortality in alcoholic liver disease (ALD), many patients struggle to achieve abstinence. Our aim was to characterize ALD patients' preferences, misconceptions, and barriers to alcohol use treatment options. METHODS: This mixed-methods study included outpatients with a history of alcohol-related cirrhosis or alcoholic hepatitis recruited from a hepatology clinic for a survey or an in-depth semi-structured interview. We purposefully sampled men and women, compensated and decompensated patients to ensure adequate representation of gender and severity of liver disease for the qualitative interviews...
August 2018: Journal of Substance Abuse Treatment
https://www.readbyqxmd.com/read/29909691/pharmacokinetics-tissue-distribution-bioavailability-and-excretion-of-nuciferine-an-alkaloid-from-lotus-in-rats-by-lc-ms-ms
#13
Fugang Wang, Juan Cao, Xueqin Hou, Zhiyong Li, Xiaolan Qu
OBJECTIVE: In order to characterize the pharmacokinetics, tissue distribution, bioavailability and excretion of nuciferine, a reliable gradient LC/MS/MS-based method was developed and validated. METHODS: Sprague-Dawley rats were intravenously injected with a bolus of nuciferine (0.2 mg/kg) and orally given a single dose of nuciferine (10.0 mg/kg). Blood samples were withdrawn via the ocular vein at specific times. Organs including the liver, kidney, brain, lung, heart and spleen were collected at specific times after oral administration of 10...
June 18, 2018: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/29909604/upregulation-of-high-mobility-group-box-1-may-contribute-to-the-pathogenesis-of-biliary-atresia
#14
Chun Jing Ye, Jiang Wang, Yi Fan Yang, Zhen Shen, Gong Chen, Yan Lei Huang, Yi Jie Zheng, Rui Dong, Shan Zheng
OBJECTIVES:  Biliary atresia (BA) is a progressive inflammatory obstructive cholangiopathy in infants. High mobility group box 1 (HMGB1) is known to play an important role as a late mediator of inflammation. However, it is not clear whether HMGB1 levels are of clinical significance in patients with BA. The aim of this study was to determine correlations between serum HMGB1 levels and the clinicopathologic features of BA. MATERIALS AND METHODS:  Serum samples were collected from 19 infants with BA, 7 infants with anicteric choledochal cysts (CC) and normal liver function, and 8 healthy controls...
June 17, 2018: European Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/29909069/antimalarial-activity-of-single-dose-dsm265-a-novel-plasmodium-dihydroorotate-dehydrogenase-inhibitor-in-patients-with-uncomplicated-plasmodium-falciparum-or-plasmodium-vivax-malaria-infection-a-proof-of-concept-open-label-phase-2a-study
#15
Alejandro Llanos-Cuentas, Martin Casapia, Raúl Chuquiyauri, Juan-Carlos Hinojosa, Nicola Kerr, Maria Rosario, Stephen Toovey, Robert H Arch, Margaret A Phillips, Felix D Rozenberg, Jade Bath, Caroline L Ng, Annie N Cowell, Elizabeth A Winzeler, David A Fidock, Mark Baker, Jörg J Möhrle, Rob Hooft van Huijsduijnen, Nathalie Gobeau, Nada Araeipour, Nicole Andenmatten, Thomas Rückle, Stephan Duparc
BACKGROUND: DSM265 is a novel, long-duration inhibitor of plasmodium dihydroorotate dehydrogenase (DHODH) with excellent selectivity over human DHODH and activity against blood and liver stages of Plasmodium falciparum. This study aimed to assess the efficacy of DSM265 in patients with P falciparum or Plasmodium vivax malaria infection. METHODS: This proof-of-concept, open-label, phase 2a study was conducted at the Asociación Civil Selva Amazónica in Iquitos, Peru...
June 13, 2018: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29908940/a-nomogram-integrating-hepatic-reserve-and-tumor-characteristics-for-hepatocellular-carcinoma-following-curative-liver-resection
#16
Bin-Bin Cai, Ke-Qing Shi, Peng Li, Bi-Cheng Chen, Liang Shi, Philip J Johnson, Paul Lai, Hidenori Toyoda, Meng-Tao Zhou
BACKGROUND: Because of the mutual influence of liver dysfunction and malignancy, overall survival (OS) is a composite clinical endpoint in hepatocellular carcinoma (HCC). We developed a nomogram integrating albumin-bilirubin (ALBI) grade, a new index of hepatic reserve, and tumor characteristics of HCC for predicting OS following curative liver resection. METHODS: The nomogram was built to estimate the probabilities of 1, 3, and 5-y OS based on training cohort of 709 HCC, which was validated in an international independent dataset...
June 14, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29908359/statin-therapy-does-not-reduce-liver-fat-scores-in-patients-receiving-antiretroviral-therapy-for-hiv-infection
#17
Vanessa El Kamari, Corrilynn O Hileman, Pierre M Gholam, Manjusha Kulkarni, Nicholas Funderburg, Grace A McComsey
BACKGROUND & AIMS: Therapies are needed to limit progression of fatty liver diseases in patients with HIV infection. We analyzed data from a prospective study of the effects of rosuvastatin (a statin) on hepatic steatosis in HIV-positive adults. METHODS: We performed secondary analysis of data from a double-blind trial of adult patients with HIV infection (78% male; 68% African American; mean age, 46 years; body mass index, 29 kg/m2 ; HIV1 RNA<1000 copies/mL; LDL-cholesterol <130 mg/dL) receiving antiretroviral therapy...
June 13, 2018: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29908302/inhibitory-effect-of-pxr-on-ammonia-induced-hepatocyte-autophagy-via-p53
#18
Linlin Yan, Zhanfei Chen, Luxi Wu, Yongfa Su, Xiaoqian Wang, Nanhong Tang
Pregnane X Receptor (PXR), a nuclear receptor transcription factor, participates in a wide range of physiological activities, but the regulation of ammonia-induced hepatocyte autophagy by PXR is not yet clear. In this study, the levels of down-regulated LC3B-II and up-regulated SQSTM1 were found in ammonia-induced PXR-overexpressing (PXR+) liver cells, but the opposite appeared in PXR-knockdown (PXR-) liver cells. Rifampicin, a PXR-activating agent, elicits a similar effect as PXR + cells. The mechanism analysis reveals that the levels of the energy-sensitive molecule AMPKβ1 and phosphorylated AMPKβ1 (p-AMPKβ1) in PXR - cells are higher than those in control cells, whereas the levels of this molecule in PXR + cells are lower than those in control cells...
June 13, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29908121/pathological-manifestations-of-farber-disease-in-a-new-mouse-model
#19
Nadine Beckmann, Stephanie Kadow, Fabian Schumacher, Joachim R Göthert, Stefanie Kesper, Annette Draeger, Walter J Schulz-Schaeffer, Jiang Wang, Jan U Becker, Melanie Kramer, Claudine Kühn, Burkhard Kleuser, Katrin Anne Becker, Erich Gulbins
Farber disease is a rare lysosomal storage disorder resulting from acid ceramidase deficiency and subsequent ceramide accumulation. No treatments are clinically available and affected patients have a severely shortened lifespan. Due to the low incidence, the pathogenesis of Farber Disease is still poorly understood. Here, we report a novel acid ceramidase mutant mouse model that enables the study of pathogenic mechanisms of Farber Disease and ceramide accumulation. Asah1tmEx1 mice were generated by deletion of the acid ceramidase signal peptide sequence...
June 1, 2018: Biological Chemistry
https://www.readbyqxmd.com/read/29907829/multiparametric-magnetic-resonance-imaging-for-quantitation-of-liver-disease-a-two-centre-cross-sectional-observational-study
#20
Natasha McDonald, Peter J Eddowes, James Hodson, Scott I K Semple, Nigel P Davies, Catherine J Kelly, Stella Kin, Miranda Phillips, Amy H Herlihy, Timothy J Kendall, Rachel M Brown, Desley A H Neil, Stefan G Hübscher, Gideon M Hirschfield, Jonathan A Fallowfield
LiverMultiScan is an emerging diagnostic tool using multiparametric MRI to quantify liver disease. In a two-centre prospective validation study, 161 consecutive adult patients who had clinically-indicated liver biopsies underwent contemporaneous non-contrast multiparametric MRI at 3.0 tesla (proton density fat fraction (PDFF), T1 and T2* mapping), transient elastography (TE) and Enhanced Liver Fibrosis (ELF) test. Non-invasive liver tests were correlated with gold standard histothological measures. Reproducibility of LiverMultiScan was investigated in 22 healthy volunteers...
June 15, 2018: Scientific Reports
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