We developed a system for computer-assisted diagnosis (CAD) for real-time automated diagnosis of precancerous lesions and early esophageal squamous cell carcinomas (ESCCs) to assist the diagnosis of ...esophageal cancer.
A total of 6473 narrow-band imaging (NBI) images, including precancerous lesions, early ESCCs, and noncancerous lesions, were used to train the CAD system. We validated the CAD system using both endoscopic images and video datasets. The receiver operating characteristic curve of the CAD system was generated based on image datasets. An artificial intelligence probability heat map was generated for each input of endoscopic images. The yellow color indicated high possibility of cancerous lesion, and the blue color indicated noncancerous lesions on the probability heat map. When the CAD system detected any precancerous lesion or early ESCCs, the lesion of interest was masked with color.
The image datasets contained 1480 malignant NBI images from 59 consecutive cancerous cases (sensitivity, 98.04%) and 5191 noncancerous NBI images from 2004 cases (specificity, 95.03%). The area under curve was 0.989. The video datasets of precancerous lesions or early ESCCs included 27 nonmagnifying videos (per-frame sensitivity 60.8%, per-lesion sensitivity, 100%) and 20 magnifying videos (per-frame sensitivity 96.1%, per-lesion sensitivity, 100%). Unaltered full-range normal esophagus videos included 33 videos (per-frame specificity 99.9%, per-case specificity, 90.9%).
A deep learning model demonstrated high sensitivity and specificity for both endoscopic images and video datasets. The real-time CAD system has a promising potential in the near future to assist endoscopists in diagnosing precancerous lesions and ESCCs.
The spectrum of nonalcoholic fatty liver disease (NAFLD) includes a nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). The specific types and amounts of lipids that accumulate ...in NAFLD are not fully defined. The free fatty acid (FFA), diacylglycerol (DAG), triacylglycerol (TAG), free cholesterol (FC), cholesterol ester, and phospholipid contents in normal livers were quantified and compared to those of NAFL and NASH, and the distribution of fatty acids within these classes was compared across these groups. Hepatic lipids were quantified by capillary gas chromatography. The mean (nmol/g of tissue) DAG (normal/NAFL/NASH: 1922 versus 4947 versus 3304) and TAG (13,609 versus 128,585 versus 104,036) increased significantly in NAFLD, but FFA remained unaltered (5533 versus 5929 versus 6115). There was a stepwise increase in the mean TAG/DAG ratio from normal livers to NAFL to NASH (7 versus 26 versus 31, P < 0.001). There was also a similar stepwise increment in hepatic FC (7539 versus 10,383 versus 12,863, P < 0.05 for NASH). The total phosphatidylcholine (PC) decreased in both NAFL and NASH. The FC/PC ratio increased progressively (0.34 versus 0.69 versus 0.71, P < 0.008 for both). Although the levels for linoleic acid (18:2n‐6) and α‐linolenic acid (18:3n‐3) remained unaltered, there was a decrease in arachidonic acid (20:4n‐6) in FFA, TAG, and PC (P < 0.05 for all) in NASH. Eicosapentanoic acid (20:5n‐3) and docosahexanoic acid (22:6n‐3) were decreased in TAG in NASH. The n‐6:n‐3 FFA ratio increased in NASH (P < 0.05). Conclusions: NAFLD is associated with numerous changes in the lipid composition of the liver. The potential implications are discussed. (HEPATOLOGY 2007.)
Background & Aims: Nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) are associated with known triggers of the unfolded protein response (UPR). The aims were to (1) evaluate the ...activity of UPR in NAFL and NASH and (2) correlate expression of UPR pathways with liver histology. Methods: Messenger RNA (mRNA) and protein expression were measured by quantitative real-time PCR and Western blot, respectively. Apoptosis was assessed by TUNEL assay. Liver histology was scored using the NASH clinical research network criteria. Results: Compared with subjects with the metabolic syndrome and normal liver histology (n = 17), both NAFL (n = 21) and NASH (n = 21) were associated with increased eukaryotic initiation factor-2α (eIF-2α) phosphorylation. Activating transcription factor 4 (ATF4) mRNA and protein, C/EBP homologous protein (CHOP), and growth arrest, DNA damage-34 (GADD34) mRNA were not increased in NAFL or NASH. Whereas immunoglobulin heavy chain binding protein mRNA was significantly increased in NASH, unspliced X-box protein-1 (XBP-1) protein did not increase. Also, endoplasmic reticulum degradation-enhancing α-mannosidase-like protein mRNA levels were inversely related to spliced XBP-1 mRNA in NASH. NASH was specifically associated with low sXBP-1 protein and increased JNK phosphorylation. This correlated with increased TUNEL activity in NASH. The histologic severity correlated with sXBP-1 mRNA and JNK phosphorylation. Conclusions: There is a variable degree of UPR activation in NAFL and NASH. Although both NAFL and NASH are associated with eIF-2α phosphorylation, there is a failure to activate downstream recovery pathways, ie, ATF4-CHOP-GADD34. NASH is specifically associated with (1) failure to generate sXBP-1 protein and (2) activation of JNK.
Specific alterations in hepatic lipid composition characterize the spectrum of nonalcoholic fatty liver disease (NAFLD), which extends from nonalcoholic fatty liver (NAFL) to nonalcoholic ...steatohepatitis (NASH). However, the plasma lipidome of NAFLD and whether NASH has a distinct plasma lipidomic signature are unknown. A comprehensive analysis of plasma lipids and eicosanoid metabolites quantified by mass spectrometry was performed in NAFL (n = 25) and NASH (n = 50) subjects and compared with lean normal controls (n = 50). The key findings include significantly increased total plasma monounsaturated fatty acids driven by palmitoleic (16:1 n7) and oleic (18:1 n9) acids content (P < 0.01 for both acids in both NAFL and NASH). The levels of palmitoleic acid, oleic acid, and palmitoleic acid to palmitic acid (16:0) ratio were significantly increased in NAFLD across multiple lipid classes. Linoleic acid (8:2n6) was decreased (P < 0.05), with a concomitant increase in γ‐linolenic (18:3n6) and dihomo γ‐linolenic (20:3n6) acids in both NAFL and NASH (P < 0.001 for most lipid classes). The docosahexanoic acid (22:6 n3) to docosapentenoic acid (22:5n3) ratio was significantly decreased within phosphatidylcholine (PC), and phosphatidylethanolamine (PE) pools, which was most marked in NASH subjects (P < 0.01 for PC and P < 0.001 for PE). The total plasmalogen levels were significantly decreased in NASH compared with controls (P < 0.05). A stepwise increase in lipoxygenase (LOX) metabolites 5(S)‐hydroxyeicosatetraenoic acid (5‐HETE), 8‐HETE, and 15‐HETE characterized progression from normal to NAFL to NASH. The level of 11‐HETE, a nonenzymatic oxidation product of arachidonic (20:4) acid, was significantly increased in NASH only. Conclusions: Although increased lipogenesis, desaturases, and LOX activities characterize NAFL and NASH, impaired peroxisomal polyunsaturated fatty acid (PUFA) metabolism and nonenzymatic oxidation is associated with progression to NASH. (HEPATOLOGY 2009;50:1827–1838.)
Nonalcoholic fatty liver disease (NAFLD) is the most common liver abnormality in the United States and is strongly associated with the metabolic syndrome. Although many of the risk factors are well ...defined, the pathogenesis of NAFLD remains poorly understood. Recent studies have implicated several important cellular processes and signaling pathways that are affected by abnormal lipid metabolism, resulting in specific biochemical, histological, and clinical changes associated with NAFLD. Pharmacotherapy for NAFLD is limited and treatments are mainly to minimize risk factors. Understanding the disease pathogenesis is therefore important in identifying individuals with increased susceptibility for disease progression so lifestyle and risk modifications can be initiated early on. In this review, recent advances in the study of abnormal lipid metabolism and its impacts on histology and dysregulation of various cellular processes implicated in the genesis of NAFLD will be discussed.
The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is not entirely understood. Recently, the role of microRNA in this liver disease entity and its implication in disease pathogenesis and ...therapeutic potential has advanced rapidly over the year. While the regulation of miRNA function and its mechanism of actions on translational control of target mRNA expression remain unknown, advances in miRNA research allow identification and biochemical characterization of events that limit protein expression, which is crucial in various forms of human diseases and their subsequent development. It is hoped that further understanding of the role of microRNA in NAFLD will advance potential therapeutics and preventive measures to modify and alter this disease process.
In hepatitis C virus (HCV) infection, significant hepatic steatosis or superimposed nonalcoholic steatohepatitis is associated with disease severity and poor response to antiviral therapy. ...Nonalcoholic fatty liver disease (NAFLD) and HCV are common causes of chronic liver disease in Western countries and are strongly linked to concurrent obesity, insulin resistance, and the metabolic syndrome. With the escalating prevalence of obesity in North America, insulin resistance and the metabolic syndrome are major public health problems that have a significant impact on morbidity and mortality associated with NAFLD and HCV. This article focuses on the current understanding of the interplay between host and viral factors that are involved in the interaction between NAFLD and HCV.
PURPOSE OF REVIEWThis review focuses on recent advances in the study of the epidemiology, pathogenesis, natural history and treatment of nonalcoholic fatty liver disease (NAFLD).
RECENT FINDINGSStudy ...of hepatic lipid metabolism, insulin resistance, mitochondrial dysfunction and oxidative stress, genetic variants and predisposition to altered metabolism and cell injury have contributed to our current understanding of NAFLD. Differential expression of microRNA in fatty liver and its implication in disease pathogenesis and therapeutic potential have continued to advance over the year. The pathogenesis of hepatocellular carcinoma in steatohepatitis continues to be explored. The diagnostic utility of imaging and noninvasive markers seems promising in estimating the severity of steatosis and fibrosis. Liver biopsy remains the gold standard for accurately assessing NAFLD and steatohepatitis. Lifestyle modification and weight loss improve both metabolic profile and liver histology. Pharmacotherapy for the treatment of NAFLD remains lacking.
SUMMARYThe underlying mechanism and pathogenesis of NAFLD remain elusive despite ongoing researches to make significant advances in the understanding of its natural history, pathogenesis and management. Pharmacotherapy has yet to indicate a promising therapeutic intervention. Current treatment focuses on managing underlying cardio-metabolic risks.
The expression of microRNA in nonalcoholic steatohepatitis (NASH) and their role in the genesis of NASH are not known. The aims of this study were to: (1) identify differentially expressed microRNAs ...in human NASH, (2) tabulate their potential targets, and (3) define the effect of a specific differentially expressed microRNA, miR‐122, on its targets and compare these effects with the pattern of expression of these targets in human NASH. The expression of 474 human microRNAs was compared in subjects with the metabolic syndrome and NASH versus controls with normal liver histology. Differentially expressed microRNAs were identified by the μParaflo microRNA microarray assay and validated using quantitative real‐time polymerase chain reaction (PCR). The effects of a specific differentially expressed miRNA (miR‐122) on its predicted targets were assessed by silencing and overexpressing miR‐122 in vitro. A total of 23 microRNAs were underexpressed or overexpressed. The predicted targets of these microRNAs are known to affect cell proliferation, protein translation, apoptosis, inflammation, oxidative stress, and metabolism. The miR‐122 level was significantly decreased in subjects with NASH (63% by real‐time PCR, P < 0.00001). Silencing miR‐122 led to an initial increase in mRNA levels of these targets (P < 0.05 for all) followed by a decrease by 48 hours. This was accompanied by an increase in protein levels of these targets (P < 0.05 for all). Overexpression of miR‐122 led to a significant decrease in protein levels of these targets. Conclusions: NASH is associated with altered hepatic microRNA expression. Underexpression of miR‐122 potentially contributes to altered lipid metabolism implicated in the pathogenesis of NASH. (HEPATOLOGY 2008;48:1810–1820.)
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