Browsing by Subject "steatosis"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    The Activation and Function of Autophagy in Alcoholic Liver Disease
    (Bentham Science Publishers, 2017) Khambu, Bilon; Wang, Lin; Zhang, Hao; Yin, Xiao-Ming; Pathology and Laboratory Medicine, School of Medicine
  • Thumbnail Image
    Item
    Apolipoprotein B and PNPLA3 Double Heterozygosity in a Father–Son Pair With Advanced Nonalcoholic Fatty Liver Disease
    (Wiley, 2019) Jansson-Knodell, Claire L.; Gawrieh, Samer; McIntyre, Adam D.; Liang, Tiebing; Hegele, Robert A.; Chalasani, Naga; Medicine, School of Medicine
  • Thumbnail Image
    Item
    Development and Validation of Hepamet Fibrosis Scoring System A Simple, Noninvasive Test to Identify Patients With Nonalcoholic Fatty Liver Disease With Advanced Fibrosis
    (Elsevier, 2019) Ampuero, Javier; Pais, Raluca; Aller, Rocío; Gallego-Durán, Rocío; Crespo, Javier; García-Monzón, Carmelo; Boursier, Jerome; Vilar, Eduardo; Petta, Salvatore; Ming-Hua, Zheng; Escudero, Desamparados; Calleja, Jose Luis; Aspichueta, Patricia; Diago, Moisés; Rosales, Jose Miguel; Caballería, Joan; Gómez-Camarero, Judith; Lo Iacono, Oreste; Benlloch, Salvador; Albillos, Agustín; Turnes, Juan; Banales, Jesus M.; Ratziu, Vlad; Romero-Gómez, Manuel; Medicine, School of Medicine
    Background & Aims Fibrosis affects prognoses for patients with nonalcoholic fatty liver disease (NAFLD). Several non-invasive scoring systems have aimed to identify patients at risk for advanced fibrosis, but inconclusive results and variations in features of patients (diabetes, obesity and older age) reduce their diagnostic accuracy. We sought to develop a scoring system based on serum markers to identify patients with NAFLD at risk for advanced fibrosis. Methods We collected data from 2452 patients with NAFLD at medical centers in Italy, France, Cuba, and China. We developed the Hepamet fibrosis scoring system using demographic, anthropometric, and laboratory test data, collected at time of liver biopsy, from a training cohort of patients from Spain (n = 768) and validated the system using patients from Cuba (n = 344), Italy (n = 288), France (n = 830), and China (n = 232). Hepamet fibrosis score (HFS) were compared with those of previously developed fibrosis scoring systems (the NAFLD fibrosis score [NFS] and FIB-4). The diagnostic accuracy of the Hepamet fibrosis scoring system was assessed based on area under the receiver operating characteristic (AUROC) curve, sensitivity, specificity, diagnostic odds ratio, and positive and negative predictive values and likelihood ratios. Results Variables used to determine HFS were patient sex, age, homeostatic model assessment score, presence of diabetes, levels of aspartate aminotransferase, and albumin, and platelet counts; these were independently associated with advanced fibrosis. HFS discriminated between patients with and without advanced fibrosis with an AUROC curve value of 0.85 whereas NFS or FIB-4 did so with AUROC values of 0.80 (P = .0001). In the validation set, cut-off HFS of 0.12 and 0.47 identified patients with and without advanced fibrosis with 97.2% specificity, 74% sensitivity, a 92% negative predictive value, a 76.3% positive predictive value, a 13.22 positive likelihood ratio, and a 0.31 negative likelihood ratio. HFS were not affected by patient age, body mass index, hypertransaminasemia, or diabetes. The Hepamet fibrosis scoring system had the greatest net benefit in identifying patients who should undergo liver biopsy analysis and led to significant improvements in reclassification, reducing the number of patients with undetermined results to 20% from 30% for the FIB-4 and NFS systems (P < .05). Conclusions Using clinical and laboratory data from patients with NAFLD, we developed and validated the Hepamet fibrosis scoring system, which identified patients with advanced fibrosis with greater accuracy than the FIB-4 and NFS systems. the Hepamet system provides a greater net benefit for the decision-making process to identify patients who should undergo liver biopsy analysis.
  • Thumbnail Image
    Item
    The inhibitory effect of ethanol on Sestrin3 in the pathogenesis of ethanol-induced liver injury
    (American Physiological Society (APS), 2014-07-01) Kang, Xinqin; Petyaykina, Kateryna; Tao, Rongya; Xiong, Xiwen; Dong, X. Charlie; Liangpunsaku, Suthat; Department of Medicine, IU School of Medicine
    Sestrins (Sesns) are a family of stress-sensitive genes that have been suggested to regulate lipid metabolism. Chronic ethanol feeding is known to cause lipid accumulation in hepatocytes. This study was designed to investigate the role of Sesn3 in the pathogenesis of alcohol-induced hepatic steatosis. We demonstrated that ethanol inhibited the expression of Sesn3 in VL-17A cells. Overexpression of Sesn3 ameliorated triglyceride accumulation; downregulation using short hairpin RNA significantly deteriorated triglyceride accumulation in these cells. The expression of Sesn3 was also reduced in mice fed with ethanol for 4 wk. Overexpression of Sesn3 prevented hepatic steatosis, whereas knockdown of Sesn3 worsened hepatic steatosis in ethanol-fed mice. Overexpression of Sesn3 significantly reduced the expression of genes encoding for lipid synthesis through AMPK pathway. Overexpression of Sesn3 augmented the effect of ethanol on phospho-p70 S6 kinase. The levels of hepatic light chain 3, a marker for autophagy, expression were significantly decreased in ethanol-fed mice after Sesn3 gene was knocked down. Our findings suggest that inhibitory effect of ethanol on Sesn3 may play an important role in the development of ethanol-induced fatty liver.
  • Thumbnail Image
    Item
    Sesn3 protects against diet‐induced nonalcoholic steatohepatitis in mice via suppression of the TGFβ signal transduction
    (Wiley, 2019) Huang, Menghao; Kim, Hyeong Geug; Zhong, Xiaolin; Dong, Chuanpeng; Zhang, Brian; Fang, Zhigang; Zhang, Yang; Lu, Xiaoyu; Saxena, Romil; Liu, Yunlong; Zhang, Chi; Liangpunsakul, Suthat; Dong, X. Charlie; Medicine, School of Medicine
    Sesn3 belongs to the three‐member sestrin protein family. Sestrins have been implicated in anti‐oxidative stress, AMPK and mTOR signal transduction, and metabolic homeostasis. However, the role of Sesn3 in the development of nonalcoholic steatohepatitis (NASH) has not been previously studied. In this work, we generated Sesn3 whole‐body knockout and liver‐specific transgenic mice to investigate the hepatic function of Sesn3 in diet‐induced NASH. With only 4 weeks of dietary treatment, Sesn3 knockout mice developed severe NASH phenotype as characterized by hepatic steatosis, inflammation, and fibrosis. Strikingly, after 8‐week feeding with a NASH‐inducing diet, Sesn3 transgenic mice were largely protected against NASH development. Transcriptomic analysis revealed that multiple extracellular matrix related processes were upregulated including TGFβ signaling and collagen production. Further biochemical and cell biological analyses have illustrated a critical control of the TGFβ‐Smad pathway by Sesn3 at the TGFβ receptor and Smad3 levels. First, Sesn3 inhibits the TGFβ receptor through an interaction with Smad7; second, Sesn3 directly inhibits the Smad3 function through protein‐protein interaction and cytosolic retention.