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Liver fibrosis

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https://www.readbyqxmd.com/read/28329108/increased-mortality-among-persons-with-chronic-hepatitis-c-with-moderate-or-severe-liver-disease-a-cohort-study
#1
Javier A Cepeda, David L Thomas, Jacquie Astemborski, Mark S Sulkowski, Gregory D Kirk, Shruti H Mehta
Background: Despite the availability of curative treatment for hepatitis C virus (HCV) infection, because of cost, treatment is often denied until liver fibrosis has progressed to at least moderate fibrosis and in some cases cirrhosis. That practice is justified on assumptions that there are no medical consequences to having moderate disease and that disease stage transitions can be anticipated. Methods: We performed transient elastography on 964 people chronically infected with HCV with a history of injection drug use living in Baltimore, Maryland...
March 10, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28328941/cynomolgus-monkeys-are-successfully-and-persistently-infected-with-hepatitis-e-virus-genotype-3-hev-3-after-long-term-immunosuppressive-therapy
#2
Noemi Rovaris Gardinali, Juliana Rodrigues Guimarães, Juliana Gil Melgaço, Yohan Britto Kevorkian, Fernanda de Oliveira Bottino, Yasmine Rangel Vieira, Aline Campos de Azevedo da Silva, Douglas Pereira Pinto, Laís Bastos da Fonseca, Leandro Schiavo Vilhena, Edilson Uiechi, Maria Cristina Carlan da Silva, Julio Moran, Renato Sérgio Marchevsky, Oswaldo Gonçalves Cruz, Rodrigo Alejandro Arellano Otonel, Amauri Alcindo Alfieri, Jaqueline Mendes de Oliveira, Ana Maria Coimbra Gaspar, Marcelo Alves Pinto
Epidemiological studies found that hepatitis E virus genotype 3 (HEV-3) infection was associated with chronic hepatitis and cirrhosis in immunocompromised patients. Our study aimed to investigate the relationship between the host immunosuppressive status and the occurrence of HEV-related chronic hepatitis. Here we describe a successful experimental study, using cynomolgus monkeys previously treated with tacrolimus, a potent calcineurin inhibitor immunosuppressant, and infected with a Brazilian HEV-3 strain isolated from naturally infected pigs...
2017: PloS One
https://www.readbyqxmd.com/read/28328813/evaluation-of-apri-and-fib-4-for-noninvasive-assessment-of-significant-fibrosis-and-cirrhosis-in-hbeag-negative-chb-patients-with-alt%C3%A2-%C3%A2-%C3%A2-2-uln-a-retrospective-cohort-study
#3
Qiang Li, Xiaojing Ren, Chuan Lu, Weixia Li, Yuxian Huang, Liang Chen
To evaluate the performance of aspartate transaminase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) to predict significant fibrosis and cirrhosis in hepatitis B virus e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with alanine transaminase (ALT) ≤ twice the upper limit of normal (2 ULN).Histologic and laboratory data of 236 HBeAg-negative CHB patients with ALT ≤ 2 ULN were analyzed. Predicted fibrosis stage, based on established scales and cut-offs for APRI and FIB-4, was compared with METAVIR scores obtained from liver biopsy...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28327670/global-identification-and-analysis-of-isozyme-specific-possible-substrates-crosslinked-by-transglutaminases-using-substrate-peptides-in-mouse-liver-fibrosis
#4
Hideki Tatsukawa, Yuji Tani, Risa Otsu, Haruka Nakagawa, Kiyotaka Hitomi
The transglutaminase (TG) family comprises eight isozymes that form the isopeptide bonds between glutamine and lysine residues and contribute to the fibrotic diseases via crosslinking-mediated stabilization of ECM and the activation of TGF-β in several tissues. However, despite a growing body of evidence implicating TG2 as a key enzyme in fibrosis, the causative role of TG2 and the involvement of the other isozymes have not yet been fully elucidated. Therefore, here we clarified the distributions of TG isozymes and their in situ activities and identified the isozyme-specific possible substrates for both TG1 and TG2 using their substrate peptides in mouse fibrotic liver...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28327434/-99m-tc-3prgd2-scintigraphy-to-stage-liver-fibrosis-and-evaluate-reversal-after-fibrotic-stimulus-withdrawn
#5
Xin Zhang, Qiyong Guo, Yu Shi, Weina Xu, Shupeng Yu, Zhiguang Yang, Li Cao, Changping Liu, Zhoushe Zhao, Jun Xin
OBJECTIVE: Scintigraphy using 99mTc-3PRGD2 targeting integrin αvβ3 could assess activation of hepatic stellate cells (HSCs). Liver fibrogenesis is intimately associated with activation of HSCs, and the fibrolytic process is accompanied by the reduction of the activated HSCs. In this study, we aimed to evaluate the feasibility of this method to assess the severity of liver fibrosis and the reversal after the fibrotic stimulus withdrawal. METHODS: Liver fibrosis of different stages was induced by thioacetamide (TAA) injection for 2, 4 and 6 weeks (n = 6 for each time point)...
March 7, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28327129/short-term-overfeeding-of-zebrafish-with-normal-or-high-fat-diet-as-a-model-for-the-development-of-metabolically-healthy-versus-unhealthy-obesity
#6
Kathrin Landgraf, Susanne Schuster, Andrej Meusel, Antje Garten, Thomas Riemer, Dorit Schleinitz, Wieland Kiess, Antje Körner
BACKGROUND: Obese individuals differ in their risk of developing metabolic and cardiovascular complications depending on fat distribution (subcutaneous versus visceral) and adipose tissue (AT) phenotype (hyperplasic versus hypertrophic). However, the exact mechanisms which determine whether an obese individual is metabolically healthy or unhealthy are not clear, and analyses of the underlying pathomechanisms are limited by the lack of suitable in vivo models in which metabolically healthy versus metabolically unhealthy AT accumulation can be specifically induced...
March 21, 2017: BMC Physiology
https://www.readbyqxmd.com/read/28326574/tumour-epithelial-and-stromal-characteristics-of-hepatocellular-carcinomas-with-abundant-fibrous-stroma-fibrolamellar-versus-scirrhous-hepatocellular-carcinoma
#7
Young-Joo Kim, Hyungjin Rhee, Jeong Eun Yoo, Venancio A F Alves, Gi Jeong Kim, Hye Min Kim, Paulo Herman, Aline Chagas, Haeryoung Kim, Young Nyun Park
AIMS: The scirrhous variant of hepatocellular carcinoma (S-HCC) and fibrolamellar HCC (FL-HCC) are less common subtypes of HCC that are characterised by abundant fibrous stroma. Here, we aimed to investigate differences in the tumour microenvironment and the tumour epithelial cell characteristics of S-HCC and FL-HCC. METHODS AND RESULTS: Whole tissue sections of 17 S-HCCs and 9 FL-HCCs were subjected to immunohistochemical stains for K7, K19, EpCAM, CD56/NCAM, CD163, CD68, pSTAT3, FAP, CCN2 and Ki-67...
March 22, 2017: Histopathology
https://www.readbyqxmd.com/read/28325896/egg-antigen-p40-of-schistosoma-japonicum-promotes-senescence-in-activated-hepatic-stellate-cells-via-skp2-p27-signaling-pathway
#8
Tianhua Xu, Jinling Chen, Dandan Zhu, Liuting Chen, Jianxin Wang, Xiaolei Sun, Bin Hu, Yinong Duan
Schistosomiasis is characterized by egg deposition, granulomatous inflammatory reaction and then subsequent hepatic fibrosis formation. Activated HSCs are regarded as the main effector cells in the progression of liver fibrosis and induction of senescence in hepatic stellate cells (HSCs) is vital to the reversion of hepatic fibrosis. Our previous work has showed that S. japonicum egg antigen p40 (Sjp40) could promote HSCs senescence via a STAT3/p53/p21 mechanism. In this paper, the major aim was to explore whether there are other signaling pathways in the process of Sjp40-induced HSCs aging and the underlying effect of SKP2/P27 signal pathway in this procedure...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28323124/cd44-is-a-key-player-in-non-alcoholic-steatohepatitis
#9
Stéphanie Patouraux, Déborah Rousseau, Stéphanie Bonnafous, Cynthia Lebeaupin, Carmelo Luci, Clémence M Canivet, Anne-Sophie Schneck, Adeline Bertola, Marie-Christine Saint-Paul, Antonio Iannelli, Jean Gugenheim, Rodolphe Anty, Albert Tran, Béatrice Bailly-Maitre, Philippe Gual
BACKGROUND: CD44 is expressed on many immune cells that contribute to inflammation. It has been shown, mainly through animal data, that CD44 regulates adipose tissue inflammation in obesity and hepatic leukocyte recruitment in a lithogenic context. However, its role in hepatic inflammation in a mouse model of steatohepatitis and its relevance in humans have not yet been investigated. METHODS: The role of CD44 was evaluated in CD44-/- mice and after injections of an αCD44 antibody in Wild-type mice challenged with a methionine- and choline-deficient diet (MCDD)...
March 16, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28322443/all-trans-retinoic-acid-ameliorates-hepatic-stellate-cell-activation-via-suppression-of-thioredoxin-interacting-protein-expression
#10
Hiroki Shimizu, Toshiaki Tsubota, Keita Kanki, Goshi Shiota
Activation of hepatic stellate cells (HSCs) is the effector factor of hepatic fibrosis and hepatocellular carcinoma (HCC) development. Accumulating evidence suggests that retinoic acids (RAs), derivatives of vitamin A, contribute to prevention of liver fibrosis and carcinogenesis, however, regulatory mechanisms of RAs still remain exclusive. To elucidate RA signaling pathway, we previously performed a genome-wide screening of RA-responsive genes by in silico analysis of RA-response elements, and identified 26 RA-responsive genes...
March 21, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28322315/quantitative-proteomic-analysis-on-activated-hepatic-stellate-cells-reversion-reveal-stat1-as-a-key-regulator-between-liver-fibrosis-and-recovery
#11
Hongyu Zhang, Fangyan Chen, Xu Fan, Cong Lin, Yunwei Hao, Handong Wei, Weiran Lin, Ying Jiang, Fuchu He
Understanding the changes of activated HSCs reversion is an essential step toward clarifying the potential roles of HSCs in the treatment of liver fibrosis. In this study, we chose adipocyte differentiation mixture to induce LX-2 cells for 2 days in vitro as reversion phase, comparing with normal cultured LX-2 cells as activation phase. Mass spectrometric-based SILAC technology was adopted to study differentially expressed proteome of LX-2 cells between reversion and activation. Compared with activated HSCs, 273 proteins showed significant differences in reverted HSCs...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28322102/gamma-glutamyl-transpeptidase-to-platelet-ratio-index-is-a-good-noninvasive-biomarker-for-predicting-liver-fibrosis-in-chinese-chronic-hepatitis-b-patients
#12
Rong-Qi Wang, Qing-Shan Zhang, Su-Xian Zhao, Xue-Min Niu, Jing-Hua Du, Hui-Juan Du, Yue-Min Nan
Objective To evaluate whether gamma-glutamyl transpeptidase to platelet ratio index (GPRI) can diagnose the extent of liver fibrosis in Chinese patients with chronic hepatitis B (CHB) infection. Methods This prospective observational study used liver biopsy results as the gold standard to evaluate the ability of GPRI to predict hepatic fibrosis compared with two other markers, the aspartate aminotransferase (AST) to platelet ratio index (APRI) and fibrosis-4 score (FIB-4). The clinical and demographic factors that affected GPRI, independent of liver fibrosis, were assessed using multivariate linear regression analyses...
December 2016: Journal of International Medical Research
https://www.readbyqxmd.com/read/28321272/future-of-liver-disease-in-the-era-of-direct-acting-antivirals-for-the-treatment-of-hepatitis-c
#13
REVIEW
Francesca Romana Ponziani, Francesca Mangiola, Cecilia Binda, Maria Assunta Zocco, Massimo Siciliano, Antonio Grieco, Gian Lodovico Rapaccini, Maurizio Pompili, Antonio Gasbarrini
Hepatitis C virus (HCV) infection has been a global health problem for decades, due to the high number of infected people and to the lack of effective and well-tolerated therapies. In the last 3 years, the approval of new direct acting antivirals characterized by high rates of virological clearance and excellent tolerability has dramatically improved HCV infection curability, especially for patients with advanced liver disease and for liver transplant recipients. Long-term data about the impact of the new direct acting antivirals on liver fibrosis and liver disease-related outcomes are not yet available, due to their recent introduction...
March 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28321170/diabetes-mellitus-insulin-resistance-and-hepatitis-c-virus-infection-a-contemporary-review
#14
Anne-Claire Desbois, Patrice Cacoub
AIM: To summarise the literature data on hepatitis C virus (HCV)-infected patients concerning the prevalence of glucose abnormalities and associated risk. METHODS: We conducted a PubMed search and selected all studies found with the key words "HCV" or "hepatitis C virus" and "diabetes" or "insulin resistance". We included only comparative studies written in English or in French, published from January 2000 to April 2015. We collected the literature data on HCV-infected patients concerning the prevalence of glucose abnormalities [diabetes mellitus (DM) and insulin resistance (IR)] and associated risk [i...
March 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28321050/alteration-of-gut-microbial-community-after-n-n-dimethylformamide-exposure
#15
Man Zhang, Min Zheng, Zhijun Wu, Mingyue Guan, Shuai Liu, Wenjin Zhao, Juan Cheng
N,N-Dimethylformamide (DMF), a solvent commonly used in factories, can induce liver toxicities, including hepatitis, fibrosis, cirrhosis and hepatoma. It is well known that the gut microbial community plays a role in the metabolism of many toxic substance and in liver regeneration. However, the effect of DMF on rat gut microbial community is poorly understood. The gut microbiotas in control rats and rats exposed to DMF were characterized by high-throughput sequencing of the bacterial 16S rRNA gene. The levels of biochemical parameters in the serum of rats, including cholesterol, bile acid, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), were evaluated...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28320214/progression-of-liver-disease-in-children-and-adults-with-lysosomal-acid-lipase-deficiency
#16
Barbara K Burton, Nancy Silliman, Sachin Marulkar
BACKGROUND AND OBJECTIVE: Manifestations of the autosomal recessive disorder lysosomal acid lipase deficiency (LAL-D) include hepatomegaly, elevated serum liver enzymes, and progressive liver disease. We report an analysis of time to progression from first clinical manifestation to first documentation of hepatic fibrosis, cirrhosis, or liver transplantation from an observational study of pediatric and adult patients with LAL-D (clinical trial registration: NCT01528917). METHODS: Data were analyzed from 31 patients with available biopsy data and 1 patient without biopsy data who had undergone liver transplantation...
March 21, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28320106/ctrp3-attenuates-hepatic-stellate-cell-activation-through-transforming-growth-factor-%C3%AE-smad-signaling-pathway
#17
Chuantao Cheng, Shuo Yu, Ran Kong, Qinggong Yuan, Yuefeng Ma, Wenbin Yang, Gang Cao, Liyi Xie
Activation of hepatic stellate cells (HSCs) plays a pivotal role in the development of liver fibrosis. C1q/tumor necrosis factor-related protein 3 (CTRP3), a member of CTRPs, was involved in fibrosis. However, little is known about the role of CTRP3 in liver fibrosis. This study aimed to determine its role in liver fibrosis and explore the possible mechanism. Our results demonstrated that CTRP3 was lowly expressed in liver fibrosis tissues and activated HSCs. Overexpression of CTRP3 inhibited the proliferation and migration of HSCs, as well as suppressed the expression of extracellular matrix (ECM) in transforming growth factor-β1 (TGF-β1)-stimulated HSC-T6 cells...
March 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28320105/anti-fibrotic-potential-of-human-umbilical-cord-mononuclear-cells-and-mouse-bone-marrow-cells-in-ccl4-induced-liver-fibrosis-in-mice
#18
Nageh Ahmed Elmahdy, Samia Salem Sokar, Mohamed Labib Salem, Naglaa Ibrahim Sarhan, Sherin Hamed Abou-Elela
Liver fibrosis is the consequence of hepatocyte injury that leads to the activation of hepatic stellate cells (HSC). The treatment of choice is Liver transplantation; however, it has many problems such as surgery-related complications, immunological rejection and high costs associated with the procedure. Stem cell-based therapy would be a potential alternative, so the aim of this study is to investigate the therapeutic potential of human umbilical cord mononuclear cells (MNC) and mouse bone marrow cells (BMC) against carbon tetrachloride (CCl4) induced liver fibrosis in mice and compare it with that of silymarin...
March 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28320086/antifibrotic-effect-of-diethylcarbamazine-combined-with-hesperidin-against-ethanol-induced-liver-fibrosis-in-rats
#19
Alaa El-Din El-Sayed El-Sisi, Samia Salim Sokar, Abdelhadi Mohamed Shebl, Dina Zakaria Mohamed
Chronic alcohol consumption leads to extracellular matrix hyperplasia and liver fibrosis with a great role of hepatic stellate cell (HSC) activation in this process. The present study was designed to investigate the possible protective effects of diethylcarbamazine (DEC) (50mg/kg, acting as an anti-inflammatory drug, interferes with the arachidonic acid metabolism) when administrated in combination with hesperidin (HDN) (200mg/kg, a flavanone glycoside with potent antioxidant and anti-inflammatory activities) against alcoholic liver fibrosis in wistar rats compared to silymarin (Sil) (100mg/kg)...
March 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28319602/low-hepatic-tissue-copper-in-pediatric-non-alcoholic-fatty-liver-disease
#20
Michael Mendoza, Shelley Caltharp, Ming Song, Lindsay Collin, Juna V Konomi, Craig J McClain, Miriam B Vos
OBJECTIVE: Animal models and studies in adults have demonstrated that copper restriction increases severity of liver injury in non-alcoholic fatty liver disease (NAFLD). This has not been studied in children. We aimed to determine if lower tissue copper is associated with increased NAFLD severity in children. METHODS: This was a retrospective study of pediatric patients who had a liver biopsy including a hepatic copper quantitation. The primary outcome compared hepatic copper concentration in NAFLD versus non-NAFLD...
March 17, 2017: Journal of Pediatric Gastroenterology and Nutrition
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