The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Koichi Aiura - One of the best experts on this subject based on the ideXlab platform.
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development of a novel mouse model of hepatocellular carcinoma with nonalcoholic steatohepatitis using a high fat choline deficient diet and intraperitoneal injection of diethylnitrosamine
BMC Gastroenterology, 2016Co-Authors: Norihiro Kishida, Sachiko Matsuda, Osamu Itano, Masahiro Shinoda, Minoru Kitago, Hiroshi Yagi, Yuta Abe, Taizo Hibi, Yohei Masugi, Koichi AiuraAbstract:Background The incidence of hepatocellular carcinoma with nonalcoholic steatohepatitis is increasing, and its clinicopathological features are well established. Several animal models of nonalcoholic steatohepatitis have been developed to facilitate its study; however, few fully recapitulate all its clinical features, which include insulin resistance, inflammation, fibrosis, and carcinogenesis. Moreover, these models require a relatively long time to produce hepatocellular carcinoma reliably. The aim of this study was to develop a mouse model of hepatocellular carcinoma with nonalcoholic steatohepatitis that develops quickly and reflects all clinically relevant features.
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development of a novel mouse model of hepatocellular carcinoma with nonalcoholic steatohepatitis using a high fat choline deficient diet and intraperitoneal injection of diethylnitrosamine
BMC Gastroenterology, 2016Co-Authors: Norihiro Kishida, Sachiko Matsuda, Osamu Itano, Masahiro Shinoda, Minoru Kitago, Hiroshi Yagi, Yuta Abe, Taizo Hibi, Yohei Masugi, Koichi AiuraAbstract:The incidence of hepatocellular carcinoma with nonalcoholic steatohepatitis is increasing, and its clinicopathological features are well established. Several animal models of nonalcoholic steatohepatitis have been developed to facilitate its study; however, few fully recapitulate all its clinical features, which include insulin resistance, inflammation, fibrosis, and carcinogenesis. Moreover, these models require a relatively long time to produce hepatocellular carcinoma reliably. The aim of this study was to develop a mouse model of hepatocellular carcinoma with nonalcoholic steatohepatitis that develops quickly and reflects all clinically relevant features. Three-week-old C57BL/6J male mice were fed either a standard diet (MF) or a choline-deficient, high-fat diet (HFCD). The mice in the MF + diethylnitrosamine (DEN) and HFCD + DEN groups received a one-time intraperitoneal injection of DEN at the start of the respective feeding protocols. The mice in the HFCD and HFCD + DEN groups developed obesity early in the experiment and insulin resistance after 12 weeks. Triglyceride levels peaked at 8 weeks for all four groups and decreased thereafter. Alanine aminotransferase levels increased every 4 weeks, with the HFCD and HFCD + DEN groups showing remarkably high levels; the HFCD + DEN group presented the highest incidence of nonalcoholic steatohepatitis. The levels of fibrosis and steatosis varied, but they tended to increase every 4 weeks in the HFCD and HFCD + DEN groups. Computed tomography scans indicated that all the HFCD + DEN mice developed hepatic tumors from 20 weeks, some of which were glutamine synthetase-positive. The nonalcoholic steatohepatitis-hepatocellular carcinoma model we describe here is simple to establish, results in rapid tumor formation, and recapitulates most of the key features of nonalcoholic steatohepatitis. It could therefore facilitate further studies of the development, oncogenic potential, diagnosis, and treatment of this condition.
Norihiro Kishida - One of the best experts on this subject based on the ideXlab platform.
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development of a novel mouse model of hepatocellular carcinoma with nonalcoholic steatohepatitis using a high fat choline deficient diet and intraperitoneal injection of diethylnitrosamine
BMC Gastroenterology, 2016Co-Authors: Norihiro Kishida, Sachiko Matsuda, Osamu Itano, Masahiro Shinoda, Minoru Kitago, Hiroshi Yagi, Yuta Abe, Taizo Hibi, Yohei Masugi, Koichi AiuraAbstract:Background The incidence of hepatocellular carcinoma with nonalcoholic steatohepatitis is increasing, and its clinicopathological features are well established. Several animal models of nonalcoholic steatohepatitis have been developed to facilitate its study; however, few fully recapitulate all its clinical features, which include insulin resistance, inflammation, fibrosis, and carcinogenesis. Moreover, these models require a relatively long time to produce hepatocellular carcinoma reliably. The aim of this study was to develop a mouse model of hepatocellular carcinoma with nonalcoholic steatohepatitis that develops quickly and reflects all clinically relevant features.
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development of a novel mouse model of hepatocellular carcinoma with nonalcoholic steatohepatitis using a high fat choline deficient diet and intraperitoneal injection of diethylnitrosamine
BMC Gastroenterology, 2016Co-Authors: Norihiro Kishida, Sachiko Matsuda, Osamu Itano, Masahiro Shinoda, Minoru Kitago, Hiroshi Yagi, Yuta Abe, Taizo Hibi, Yohei Masugi, Koichi AiuraAbstract:The incidence of hepatocellular carcinoma with nonalcoholic steatohepatitis is increasing, and its clinicopathological features are well established. Several animal models of nonalcoholic steatohepatitis have been developed to facilitate its study; however, few fully recapitulate all its clinical features, which include insulin resistance, inflammation, fibrosis, and carcinogenesis. Moreover, these models require a relatively long time to produce hepatocellular carcinoma reliably. The aim of this study was to develop a mouse model of hepatocellular carcinoma with nonalcoholic steatohepatitis that develops quickly and reflects all clinically relevant features. Three-week-old C57BL/6J male mice were fed either a standard diet (MF) or a choline-deficient, high-fat diet (HFCD). The mice in the MF + diethylnitrosamine (DEN) and HFCD + DEN groups received a one-time intraperitoneal injection of DEN at the start of the respective feeding protocols. The mice in the HFCD and HFCD + DEN groups developed obesity early in the experiment and insulin resistance after 12 weeks. Triglyceride levels peaked at 8 weeks for all four groups and decreased thereafter. Alanine aminotransferase levels increased every 4 weeks, with the HFCD and HFCD + DEN groups showing remarkably high levels; the HFCD + DEN group presented the highest incidence of nonalcoholic steatohepatitis. The levels of fibrosis and steatosis varied, but they tended to increase every 4 weeks in the HFCD and HFCD + DEN groups. Computed tomography scans indicated that all the HFCD + DEN mice developed hepatic tumors from 20 weeks, some of which were glutamine synthetase-positive. The nonalcoholic steatohepatitis-hepatocellular carcinoma model we describe here is simple to establish, results in rapid tumor formation, and recapitulates most of the key features of nonalcoholic steatohepatitis. It could therefore facilitate further studies of the development, oncogenic potential, diagnosis, and treatment of this condition.
Rohit Loomba - One of the best experts on this subject based on the ideXlab platform.
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pnpla3 genotype and risk of liver and all cause mortality
Hepatology, 2020Co-Authors: Stefan Stender, Rohit LoombaAbstract:: Mirroring the obesity pandemic, nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease affecting populations worldwide. Approximately 30% of the adult United States (US) population is estimated to be afflicted with NAFLD. NAFLD is a spectrum of liver disease ranging from nonalcoholic fatty liver (NAFL), the non-progressive sub-type, to nonalcoholic steatohepatitis (NASH), the progressive sub-type, which can lead to progressive liver disease leading to cirrhosis and hepatocellular carcinoma(1).
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noninvasive quantitative assessment of liver fat by mri pdff as an endpoint in nash trials
Hepatology, 2018Co-Authors: Scott B Reeder, Cyrielle Caussy, Claude B Sirlin, Rohit LoombaAbstract:Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease worldwide, and the progressive form of this condition, nonalcoholic steatohepatitis (NASH), has become one of the leading indications for liver transplantation. Despite intensive investigations, there are currently no United States Food and Drug Administration-approved therapies for treating NASH. A major barrier for drug development in NASH is that treatment response assessment continues to require liver biopsy, which is invasive and interpreted subjectively. Therefore, there is a major unmet need for developing noninvasive, objective, and quantitative biomarkers for diagnosis and assessment of treatment response. Emerging data support the use of magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) as a noninvasive, quantitative, and accurate measure of liver fat content to assess treatment response in early-phase NASH trials. In this review, we discuss the role and utility, including potential sample size reduction, of MRI-PDFF as a quantitative and noninvasive imaging-based biomarker in early-phase NASH trials. Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease worldwide.() NAFLD can be broadly classified into two categories: nonalcoholic fatty liver, which has a minimal risk of progression to cirrhosis, and nonalcoholic steatohepatitis (NASH), the more progressive form of NAFLD, which has a significantly increased risk of progression to cirrhosis.() Over the past two decades, NASH-related cirrhosis has become the second leading indication for liver transplantation in the United States.() For these reasons, pharmacological therapy for NASH is needed urgently. Despite intensive investigations, there are currently no therapies for treating NASH that have been approved by the United States Food and Drug Administration.().
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genome wide associations related to hepatic histology in nonalcoholic fatty liver disease in hispanic boys
The Journal of Pediatrics, 2017Co-Authors: Julia Wattacheril, Joel E Lavine, Elizabeth M. Brunt, Jeffrey B Schwimmer, Rohit Loomba, Naga Chalasani, Xiuqing Guo, Soonil Kwon, Jean P Molleston, Yii Der Ida ChenAbstract:Objective To identify genetic loci associated with features of histologic severity of nonalcoholic fatty liver disease in a cohort of Hispanic boys. Study design There were 234 eligible Hispanic boys age 2-17 years with clinical, laboratory, and histologic data enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network included in the analysis of 624 297 single nucleotide polymorphisms (SNPs). After the elimination of 4 outliers and 22 boys with cryptic relatedness, association analyses were performed on 208 DNA samples with corresponding liver histology. Logistic regression analyses were carried out for qualitative traits and linear regression analyses were applied for quantitative traits. Results The median age and body mass index z-score were 12.0 years (IQR, 11.0-14.0) and 2.4 (IQR, 2.1-2.6), respectively. The nonalcoholic fatty liver disease activity score (scores 1-4 vs 5-8) was associated with SNP rs11166927 on chromosome 8 in the TRAPPC9 region (P = 8.7-07). Fibrosis stage was associated with SNP rs6128907 on chromosome 20, near actin related protein 5 homolog (p = 9.9-07). In comparing our results in Hispanic boys with those of previously reported SNPs in adult nonalcoholic steatohepatitis, 2 of 26 susceptibility loci were associated with nonalcoholic fatty liver disease activity score and 2 were associated with fibrosis stage. Conclusions In this discovery genome-wide association study, we found significant novel gene effects on histologic traits associated with nonalcoholic fatty liver disease activity score and fibrosis that are distinct from those previously recognized by adult nonalcoholic fatty liver disease genome-wide association studies.
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recommendations for diagnosis referral for liver biopsy and treatment of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis
Mayo Clinic proceedings, 2015Co-Authors: Erin K Spengler, Rohit LoombaAbstract:Nonalcoholic fatty liver disease (NAFLD) is the primary cause of chronic liver disease in the United States, afflicting an estimated 80 to 100 million Americans. Nonalcoholic fatty liver disease is a spectrum of liver diseases composed of nonalcoholic fatty liver and nonalcoholic steatohepatitis (NASH). Although nonalcoholic fatty liver has a negligible risk of progression, patients with NASH often develop cirrhosis or hepatocellular carcinoma. Although liver biopsy is required to diagnose NASH, only patients with a high risk of NASH or advanced fibrosis require this evaluation. Despite the high prevalence of NAFLD, well-defined screening recommendations are currently lacking. In this review, suggestions for screening, diagnosis, and initial work-up of NAFLD are given on the basis of established guidelines and recent publications. Proposed drug treatments of NASH are also discussed, highlighting the study outcomes, as well as proposed uses and limitations of these drugs. The literature was searched in PubMed using search terms nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, with filters of "English language." A date range of January 1, 2000, to May 1, 2015, was used for the search. The bibliographies of key references were also searched manually, and seminal publications before the year 2000 were included.
Silvia Fargion - One of the best experts on this subject based on the ideXlab platform.
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bloodletting ameliorates insulin sensitivity and secretion in parallel to reducing liver iron in carriers of hfe gene mutations response to equitani et al
Diabetes Care, 2008Co-Authors: Luca Valenti, Anna Ludovica Fracanzani, P Dongiovanni, Silvia FargionAbstract:Equitani et al. (1) reported on the effect of iron depletion by phlebotomy on insulin resistance and release in 17 carriers of mutations of hereditary hemochromatosis HFE gene with nonalcoholic fatty liver disease (NAFLD). They found that iron depletion ameliorated insulin sensitivity and secretion and reduced hepatic iron stores and nonalcoholic steatohepatitis activity score, and they concluded that results justify glucose tolerance testing and preventive iron depletion in asymptomatic carriers …
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tumor necrosis factor α promoter polymorphisms and insulin resistance in nonalcoholic fatty liver disease
Gastroenterology, 2002Co-Authors: Luca Valenti, G Santorelli, Anna Ludovica Fracanzani, P Dongiovanni, A Branchi, Emanuela Taioli, G Fiorelli, Silvia FargionAbstract:Background & Aims: Nonalcoholic fatty liver disease, which can range from fatty liver alone to nonalcoholic steatohepatitis and cirrhosis, is related to insulin resistance. Tumor necrosis factor α (TNF-α) may induce insulin resistance, and polymorphisms of its promoter have been associated with an increased release of this cytokine. We analyzed (1) the prevalence of insulin resistance, (2) the prevalence of the 238 and 308 TNF-α polymorphisms, and (3) the relationship among TNF-α polymorphisms, insulin resistance, and the occurrence of steatohepatitis in 99 patients with nonalcoholic fatty liver diagnosed by ultrasonography and confirmed by histologic analysis in the 53 who underwent biopsy. Methods: Insulin resistance was evaluated by the homeostatic metabolic assessment insulin resistance indices and TNF-α polymorphisms by polymerase chain reaction and restriction fragment length polymorphism analysis. Results: Insulin resistance was detected in almost all of the patients and was more severe in those with steatohepatitis. The prevalence of the 238, but not of the 308, TNF-α polymorphism was higher in subjects with nonalcoholic fatty liver than in controls (31% vs. 15%; P < 0.0001), and patients positive for TNF-α polymorphisms had higher insulin resistance indices, a higher prevalence of impaired glucose tolerance, and a lower number of associated risk factors for steatosis. Conclusions: TNF-α polymorphisms could represent a susceptibility genotype for insulin resistance, nonalcoholic fatty liver, and steatohepatitis. GASTROENTEROLOGY 2002;122:274-280
Noritoshi Kobayashi - One of the best experts on this subject based on the ideXlab platform.
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noninvasive assessment of liver fibrosis by measurement of stiffness in patients with nonalcoholic fatty liver disease nafld
Digestive and Liver Disease, 2008Co-Authors: Masashi Yoneda, Yuichi Nozaki, Hironori Mawatari, K Fujita, Hiroki Endo, Hiroshi Iida, Kyoko Yonemitsu, Takuma Higurashi, Hirokazu Takahashi, Noritoshi KobayashiAbstract:Background Liver fibrosis is the main predictor of the progression of nonalcoholic fatty liver disease. Transient elastography (FibroScan), which measures liver stiffness, is a novel, noninvasive method to assess liver fibrosis. Aim We investigated the usefulness of liver stiffness measurement in the evaluation of liver fibrosis in nonalcoholic fatty liver disease patients. Study population A total of 97 nonalcoholic fatty liver disease patients. Methods Transient elastography was performed for liver stiffness measurement in 97 nonalcoholic fatty liver disease patients. And the relationship between histological parameters and liver stiffness measurement was studied by multivariate analysis. Moreover, we investigated the relationship between liver stiffness measurement and the serum levels of hyaluronic acid and type IV collagen 7s domain. Results The liver stiffness was well correlated with the stage of liver fibrosis (Kruskal–Wallis test p < 0.0001). The areas under the receiver-operating characteristic curves were 0.927 for ≥F1, 0.865 for ≥F2, 0.904 for ≥F3, 0.991 for ≥F4. Only fibrosis stage was correlated significantly with liver stiffness measurement by multiple regression analysis. Liver stiffness was also strongly correlated with the serum levels of type IV collagen 7s domain (r = 0.525, p < 0.0001) and hyaluronic acid (r = 0.457, p < 0.0001). Conclusions Our results show a significant correlation between liver stiffness measurement and fibrosis stage in nonalcoholic fatty liver disease patients, as confirmed by the results of liver biopsy, which remains the gold standard for evaluation of the severity of liver fibrosis in patients with nonalcoholic steatohepatitis.
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noninvasive assessment of liver fibrosis by measurement of stiffness in patients with nonalcoholic fatty liver disease nafld
Digestive and Liver Disease, 2008Co-Authors: Masashi Yoneda, Yuichi Nozaki, Hironori Mawatari, K Fujita, Hiroki Endo, Hiroshi Iida, Kyoko Yonemitsu, Takuma Higurashi, Hirokazu Takahashi, Noritoshi KobayashiAbstract:BACKGROUND: Liver fibrosis is the main predictor of the progression of nonalcoholic fatty liver disease. Transient elastography (FibroScan), which measures liver stiffness, is a novel, noninvasive method to assess liver fibrosis. AIM: We investigated the usefulness of liver stiffness measurement in the evaluation of liver fibrosis in nonalcoholic fatty liver disease patients. STUDY POPULATION: A total of 97 nonalcoholic fatty liver disease patients. METHODS: Transient elastography was performed for liver stiffness measurement in 97 nonalcoholic fatty liver disease patients. And the relationship between histological parameters and liver stiffness measurement was studied by multivariate analysis. Moreover, we investigated the relationship between liver stiffness measurement and the serum levels of hyaluronic acid and type IV collagen 7s domain. RESULTS: The liver stiffness was well correlated with the stage of liver fibrosis (Kruskal-Wallis test p or = F1, 0.865 for > or = F2, 0.904 for > or = F3, 0.991 for > or = F4. Only fibrosis stage was correlated significantly with liver stiffness measurement by multiple regression analysis. Liver stiffness was also strongly correlated with the serum levels of type IV collagen 7s domain (r = 0.525, p < 0.0001) and hyaluronic acid (r = 0.457, p < 0.0001). CONCLUSIONS: Our results show a significant correlation between liver stiffness measurement and fibrosis stage in nonalcoholic fatty liver disease patients, as confirmed by the results of liver biopsy, which remains the gold standard for evaluation of the severity of liver fibrosis in patients with nonalcoholic steatohepatitis.