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hepatic fibrosis

Adam C Labonte, Sun-Sang J Sung, Lucas T Jennelle, Aditya P Dandekar, Young S Hahn
: The liver maintains an immunologically tolerant environment as a result of continuous exposure to food and bacterial constituents from the digestive tract. Hepatotropic pathogens can take advantage of this niche and establish lifelong chronic infections causing hepatic fibrosis and hepatocellular carcinoma. Macrophages (Mϕ) play a critical role in regulation of immune responses to hepatic infection and regeneration of tissue. However, the factors crucial for Mϕ in limiting hepatic inflammation or resolving liver damage have not been fully understood...
October 22, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Lamiaa Mobarak, Dalia Omran, Mohammed M Nabeel, Zeinab Zakaria
BACKGROUND AND STUDY AIM: It is well known that hepatocellular carcinoma (HCC) develops as a consequence of hepatic fibrosis progression. In this study, we aimed to evaluate the inflammatory and fibrosis markers as predictors for HCC development among patients with hepatitis C virus (HCV) related chronic liver disease to help in early diagnosis and management of HCC. METHODS: A total of 280 patients with chronic liver disease were included in this retrospective study, out of them 140 had liver cirrhosis with HCC and 140 had cirrhosis without HCC...
October 21, 2016: Journal of Medical Virology
Han-Sol Park, Jung Eun Jang, Myoung Seok Ko, Sung Hoon Woo, Bum Joong Kim, Hyun Sik Kim, Hye Sun Park, In-Sun Park, Eun Hee Koh, Ki-Up Lee
BACKGROUND: Non-alcoholic fatty liver disease is the most common form of chronic liver disease in industrialized countries. Recent studies have highlighted the association between peroxisomal dysfunction and hepatic steatosis. Peroxisomes are intracellular organelles that contribute to several crucial metabolic processes, such as facilitation of mitochondrial fatty acid oxidation (FAO) and removal of reactive oxygen species through catalase or plasmalogen synthesis. Statins are known to prevent hepatic steatosis and non-alcoholic steatohepatitis (NASH), but underlying mechanisms of this prevention are largely unknown...
October 2016: Diabetes & Metabolism Journal
Yingxue Yu, Xuehua Sun, Jinyang Gu, Chang Yu, Yankai Wen, Yueqiu Gao, Qiang Xia, Xiaoni Kong
Liver fibrosis is a global health problem and previous studies have demonstrated that reactive oxygen species (ROS) play important roles in fibrogenesis. Parkinson disease (autosomal recessive, early onset) 7 (Park7) also called DJ-1 has an essential role in modulating cellular ROS levels. DJ-1 therefore may play functions in liver fibrogenesis and modulation of DJ-1 may be a promising therapeutic approach. Here, wild-type (WT) and DJ-1 knockout (DJ-1 KO) mice were administrated with carbon tetrachloride (CCl4) to induce liver fibrosis or acute liver injury...
2016: International Journal of Biological Sciences
Morten Asser Karsdal, Kim Henriksen, Mette Juul Nielsen, Inger Byrjalsen, Diana Julie Leeming, Stephen Gardner, Zachary Goodman, Keyur Patel, Aleksander Krag, Claus Christiansen, Detlef Schuppan
BACKGROUND: There are no approved treatments for liver fibrosis. To aid development of anti-fibrotic therapies, non-invasive biomarkers that can identify patients with progressive fibrosis and that permit monitoring of the response to anti-fibrotic therapy are much needed. METHODS: Samples from a phase II anti-fibrotic trial of the glitazone farglitazar in patients with advanced hepatitis C, with matched follow-up liver biopsies, and from a phase III study of balaglitazone in late stage type 2 diabetics (BALLET study), were analysed for serological Pro-C3 levels in conjunction with other disease parameters...
October 20, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
R Jin, A Krasinskas, N-A Le, J V Konomi, J Holzberg, R Romero, M B Vos
BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is the primary inhibitor of the endogenous fibrinolytic system and is known to be increased in obesity, insulin resistance and non-alcoholic fatty liver disease (NAFLD). We previously demonstrated that PAI-1 levels were closely related to the amount of hepatic steatosis in children. OBJECTIVES: The aim of this study was to characterize plasma PAI-1 in relationship to severity of inflammation and fibrosis, as well as to plasma lipids in children with NAFLD...
October 20, 2016: Pediatric Obesity
Adil El Taghdouini, Leo A van Grunsven
Chronic liver injury to hepatocytes or cholangiocytes, when left unmanaged, leads to the development of liver fibrosis, a condition characterized by the excessive intrahepatic deposition of extracellular matrix proteins. Activated hepatic stellate cells constitute the predominant source of extracellular matrix in fibrotic livers and their transition from a quiescent state during fibrogenesis is associated with important alterations in their transcriptional and epigenetic landscape. Areas covered: We briefly describe the processes involved in hepatic stellate cell activation and discuss our current understanding of alterations in the epigenetic landscape, i...
October 20, 2016: Expert Review of Gastroenterology & Hepatology
Kenichi Morikawa, Tomoe Shimazaki, Rei Takeda, Takaaki Izumi, Machiko Umumura, Naoya Sakamoto
Hepatitis B virus (HBV) infection is a serious health threat around the world. Despite the availability of an effective hepatitis B vaccine, the number of HBV carriers is estimated to be as high as 240 million worldwide. Global mortality due to HBV-related liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC) may be as high as 1 million deaths per year. HBV is transmitted via blood and body fluids, and is much more infectious than both human immunodeficiency virus (HIV) and hepatitis C virus...
September 2016: Annals of Translational Medicine
Lingling He, Xiaoli Liu, Lijia Wang, Zhiyun Yang
The findings regarding the effects of thiazolidinediones (TZDs) in nonalcoholic steatohepatitis (NASH) patients have been inconsistent, and the assessment of different clinical variables for evaluating the effects of TZDs confound a direct comparison of the results of different randomized clinical trials (RCTs), especially with regard to lifestyle changes. In this paper, we performed a meta-analysis of randomized controlled trials to clarify the effects of TZD treatment with and without lifestyle changes on histological markers of NASH and clinical variables related to insulin resistance (IR), hyperlipidemia, and obesity...
October 2016: Medicine (Baltimore)
Huafeng Wang, Huan Zhang, Yuqing Zhang, Dan Wang, Xixi Cheng, Fengrui Yang, Qi Zhang, Zhenyi Xue, Yan Li, Lijuan Zhang, Luhong Yang, Guolin Miao, Daiqing Li, Zhiyu Guan, Yurong Da, Zhi Yao, Fei Gao, Liang Qiao, Li Kong, Rongxin Zhang
Plumbagin is a quinonoid constituent extracted from Plumbago genus, and it exhibits diverse pharmacological effects. This study thoroughly investigated the effects of plumbagin on thioacetamide-induced acute and chronic liver injury. Results shown that plumbagin increased survival rate, reduced liver congestion and inflammation, and decreased macrophages and neutrophils in the fulminant hepatic failure model, and remarkably diminished liver fibrosis and inflammation in the chronic liver injury model. Furthermore, plumbagin significantly suppress the HSCs/myofibroblasts activation by reduced expression of markers α-SMA and COL-1/3, and reduced macrophage in liver...
October 14, 2016: Oncotarget
Barbara J Turner, Yuanyuan Liang, Amit Singal
OBJECTIVES: Noninvasive measures are widely used to assess fibrosis and may be used to prioritize hepatitis C virus (HCV) treatment. We examined risks for likely fibrosis in patients with chronic HCV infection using fibrosis-4 (FIB-4) and imaging. PATIENTS AND METHODS: A HCV screening program diagnosed chronic HCV in patients born from 1945 to 1965 admitted in a safety net hospital. Likely fibrosis was based on FIB-4 (≥1.45) alone or combined with imaging interpreted as fibrosis or cirrhosis...
October 17, 2016: European Journal of Gastroenterology & Hepatology
Gretchen Bain, Kristen E Shannon, Fei Huang, Janice Darlington, Lance Goulet, Patricia Prodanovich, Gina L Ma, Angelina M Santini, Adam J Stein, Dave Lonergan, Christopher D King, Imelda Calderon, Andiliy Lai, John H Hutchinson, Jilly F Evans
Autotaxin (ATX) is a secreted glycoprotein that converts lysophosphatidylcholine (LPC) to the bioactive phospholipid lysophosphatidic acid (LPA) and is the major enzyme generating circulating LPA. Inhibition of LPA signaling has profound anti-fibrotic effects in multiple organ systems including the lung, kidney, skin and peritoneum. However, other LPA-generating pathways exist and the role of ATX in localized tissue LPA production and fibrosis remains unclear and controversial. In this study, we describe the preclinical pharmacological, pharmacokinetic and pharmacodynamic properties of a novel small-molecule ATX inhibitor [3-((6-chloro-2-cyclopropyl-1-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-1H-indol-3-yl) thio)-2-fluorobenzoic acid sodium salt] (PAT-505)...
October 17, 2016: Journal of Pharmacology and Experimental Therapeutics
Ryuichi Morishita
Recent research on vaccination has extended its scope from infectious diseases to chronic diseases, including Alzheimer disease, dyslipidemia, and hypertension. We have designed DNA vaccine for the treatment of high blood pressure (BP) toward to human vaccine therapy to treat hypertension. Plasmid vector encoding hepatitis B core-angiotensin II (Ang II) fusion protein was injected into spontaneously hypertensive rats (SHR) using needleless injection system. Anti-Ang II antibody was successfully produced in hepatitis B core-Ang II group, and antibody response against Ang II was sustained for at least 6 months...
September 2016: Journal of Hypertension
Frank W DiPaola, Kurt R Schumacher, Caren S Goldberg, Joshua Friedland-Little, Aishwarya Parameswaran, Jonathan R Dillman
OBJECTIVES: Assess liver stiffness using ultrasound point shear wave elastography (US P-SWE) in children before and after the Fontan operation. METHODS: Eighteen children undergoing the Fontan operation were prospectively enrolled. Eight US P-SWE measurements were obtained from the right hepatic lobe before surgery, and at multiple postoperative time points. Temporally related inferior vena cava pressure (IVC) data was collected from medical records, when available...
October 17, 2016: European Radiology
Yone-Han Mah, Chen-Hua Liu, Chi-Ling Chen, Tai-Chung Tseng, Chun-Jen Liu, Pei-Jer Chen, Ding-Shinn Chen, Jia-Horng Kao
BACKGROUND/PURPOSE: Clinical implications of IL28B gene in Taiwanese chronic hepatitis C (CHC) patients remain unknown. We thus investigated the prevalence and clinical implications of IL28B rs8099917 genotypes in CHC patients with different hepatitis C virus (HCV) genotypes and healthy controls. METHODS: A total of 200 HCV genotype 1 patients and 200 HCV genotype 2 patients who received liver biopsy, as well as 197 healthy controls were enrolled to determine the frequencies of IL28B rs8099917 genotypes...
October 14, 2016: Journal of the Formosan Medical Association, Taiwan Yi Zhi
Norihisa Yada, Toshiharu Sakurai, Tomohiro Minami, Tadaaki Arizumi, Masahiro Takita, Satoru Hagiwara, Hiroshi Ida, Kazuomi Ueshima, Naoshi Nishida, Masatoshi Kudo
OBJECTIVE: We have reported about real-time tissue elastography (RTE), which displays relative strain by measuring the relative distortion of the tissue, and found this information to be useful for diagnosing liver fibrosis. However, its use in predicting hepatocellular carcinoma has not been reported as yet. Here, we investigated RTE to predict liver carcinogenesis in patients with chronic hepatitis C virus (HCV) infection. METHODS: We enrolled 160 patients with chronic HCV, who were followed up for 39...
2016: Digestive Diseases
Tao Wu, Ping Wang, Ting Zhang, Jian Zheng, Shuoyang Li, Jie Zeng, Masatoshi Kudo, Rongqin Zheng
BACKGROUND: Noninvasive assessment of liver fibrosis has important clinical significance. Different techniques including two-dimensional shear-wave elastography (2D SWE) and real-time tissue elastography (RTE) are reported to be useful for the noninvasive diagnosis of hepatic fibrosis. All these techniques are affected by many factors. How to choose a reasonable method needs further studies. PURPOSE: This study was conducted to comparatively assess the diagnostic performance of 2D SWE and RTE in patients with Chronic Hepatitis B (CHB) and influence of inflammation on the stiffness values obtained by both techniques, so as to objectively assess the reasonable choice between these 2 elastography techniques for noninvasive assessment of hepatic fibrosis in clinical practice...
2016: Digestive Diseases
Naoshi Nishida, Masashi Kono, Tomohiro Minami, Hirokazu Chishina, Tadaaki Arizumi, Masahiro Takita, Norihisa Yada, Hiroshi Ida, Satoru Hagiwara, Yasunori Minami, Kazuomi Ueshima, Tashiharu Sakurai, Masatoshi Kudo
BACKGROUND: An interferon-free regimen including sofosbuvir and ribavirin (RBV) for patients with hepatitis C virus (HCV) genotype 2 (G2) infection leads to a drastic improvement of sustained virological response (SVR). However, the safety, tolerability, and efficacy in patients aged 75 or older have not been completely understood. SUMMARY: Fifty-six patients with HCV G2 infection who were treated with sofosbuvir and weight-based dose of RBV were enrolled. Thirty-seven patients aged ≥75 and 19 patients aged ≤74 were classified as the aged and non-aged groups, respectively...
2016: Digestive Diseases
Yundong Qu, Ying Guo, Tao Li, Qian Ye, Chao Sun, Lei Wang, Baohua Yang
BACKGROUND AND AIM: To assess the efficacy and safety of sofosbuvir-based interferon-free therapies in liver transplantation recipients with hepatitis C virus infection recurrence. METHODS: A systematic literature search was conducted in PubMed, EMBASE, Web of Science, and CENTRAL on the Cochrane Library without time or language limitation. The search strategy used was "sofosbuvir AND transplantation". Sustained virologic response at 12 weeks after the end of treatment (SVR12) rate, incidence of serious adverse events (SAEs) and/or adverse events (AEs), discontinuation rate with 95% confidence intervals (CI) were pooled with random-effects model...
October 17, 2016: Journal of Gastroenterology and Hepatology
Kangkang Wu, Rui Huang, Hongyan Wu, Yong Liu, Chenchen Yang, Shufeng Cao, Xianglin Hou, Bing Chen, Jianwu DaI, Chao Wu
Vascular endothelial growth factor (VEGF) serves an important role in promoting angiogenesis and tissue regeneration. However, the lack of an effective delivery system that can target this growth factor to the injured site reduces its therapeutic efficacy. Therefore, in the current study, collagen‑binding VEGF was constructed by fusing a collagen‑binding domain (CBD) to the N‑terminal of native VEGF. The CBD‑VEGF can specifically bind to collagen which is the major component of the extracellular matrix in fibrotic liver...
October 12, 2016: Molecular Medicine Reports
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