Hepatic steatosis is common in the general population and is present in 13.25% of donor organs. It can affect graft survival and recovery of the donor after partial hepatectomy. Liver biopsy is the standard method to measure the degree of hepatic steatosis, but it¡¦s also an invasive procedure and may have sampling error. Non-invasive tools, such as computed tomography and magnetic resonance image, are generally utilized and developed. This study was designed to build a standard model for the quantification of the fat content in a fat-water mixed phantom model. Pork fat and pure water were mixed in different ratios by volume (from 0% fraction of fat to 100% fat in steps of 5%), and then measured for fat content in different concentrations of fat-water mixed phantom by using (1) CT number (Hounsfield unit; HU), (2) Dixon method (in-phase & opposed-phase), and (3) 1H spectroscopy (SVS30 & SVS136, without water suppression). The CT number decreased with increasing fat concentration. The Hounsfield units of pure fat were about -122 HU. At Dixon method, the fat image intensity increased to its maximum when the fat concentration reached 25% and then decreased. Fat concentration higher than 25% and lower than 25% both had the same value of the fat image intensity. Combined with SVS30 water/fat peak height ratio, the fat concentration could be estimated. Furthermore, the fat image could be utilized to observe the topographic distribution of hepatic steatosis. Then a rat fatty liver model fed with a choline deficient and iron supplemented L-amino acid defined (CDAA) diet was established. Fatty liver grade was evaluated by radiological and biochemical assessments. CT and MRS technique displayed the highest fat contents the same with histological examination in CDAA diet rats at 6 weeks. The results showed that MRS was a suitable method for quantifying fat to water concentration. As a result of this study, model of measurement scale can be established to measure fat concentration both in phanatoms and animal. Further study in human fatty liver was expected.

published_or_final_version / Surgery / Master / Master of Research in Medicine

published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

No description available.

Introduction: Non-invasive assessment of steatosis and fibrosis is of growing relevance in non-alcoholic fatty liver disease (NAFLD). 1H-Magnetic resonance spectroscopy (1H-MRS) and the ultrasound-based controlled attenuation parameter (CAP) correlate with biopsy proven steatosis, but have not been correlated with each other so far. We therefore performed a headto- head comparison between both methods. Methods: Fifty patients with biopsy-proven NAFLD and 15 healthy volunteers were evaluated with 1H-MRS and transient elastography (TE) including CAP. Steatosis was defined according to the percentage of affected hepatocytes: S1 5-33%, S2 34–66%, S3 $67%. Results: Steatosis grade in patients with NAFLD was S1 36%, S2 40% and S3 24%. CAP and 1H-MRS significantly correlated with histopathology and showed comparable accuracy for the detection of hepatic steatosis: areas under the receiveroperating characteristics curves were 0.93 vs. 0.88 for steatosis $S1 and 0.94 vs. 0.88 for $S2, respectively. Boot-strapping analysis revealed a CAP cut-off of 300 dB/m for detection of S2-3 steatosis, while retaining the lower cut-off of 215 dB/m for the definition of healthy individuals. Direct comparison between CAP and 1H-MRS revealed only modest correlation (total cohort: r = 0.63 [0.44, 0.76]; NAFLD cases: r = 0.56 [0.32, 0.74]). For detection of F2–4 fibrosis TE had sensitivity and specificity of 100% and 98.1% at a cut-off value of 8.85 kPa. Conclusion: Our data suggest a comparable diagnostic value of CAP and 1H-MRS for hepatic steatosis quantification. Combined with the simultaneous TE fibrosis assessment, CAP represents an efficient method for non-invasive characterization of NAFLD. Limited correlation between CAP and 1H-MRS may be explained by different technical aspects, anthropometry, and presence of advanced liver fibrosis.

Thesis (Ph. D.)--University of Washington, 1999. / Vita. Includes bibliographical references (leaves 163-179).

Thesis (M.Phil.) - University of Queensland, 2005. / Includes bibliography.

Thesis (M.Phil.) - University of Queensland, 2005. / Includes bibliography.

Obesity and metabolic dysfunction are worldwide health epidemics and they have grown to unprecedented levels. Human NAFLD is directly linked to obesity and metabolic dysfunction, so attention was given to elucidating a more complete understanding of the liver's role in mediating the metabolically healthy obese phenotype and to better characterizing the potential contribution of dietary fat and fatty acids as a therapeutic supplement to obesogenic diets. Specifically, flaxseed is high in α-linolenic acid (ALA; 18:3 n-3) and low in linoleic acid (LA; 18:2 n-6), and contains multiple other components such as fiber and lignans, and was investigated for its high potential to modify obesity phenotype and fatty liver disease. Additionally, we explored the temporal effect of initiating high-fat diets in various phases of adulthood. However, work in this field is complicated by an ongoing search for appropriate preclinical animal models of NAFLD as they have not been able to replicate the full spectrum of human NAFLD. As such, this dissertation sought to explore fatty liver disease in popular murine models of overnutrition, as well as a novel hen model. Major findings from this work showed that (1) exposure to a high-fat diet during early adulthood preserves metabolic homeostasis, modifies liver morphology, and protects against obesity-related disease, (2) dietary enrichment with flaxseed is capable of increasing tissue n3PUFA content, but this appeared to be only weakly related to metabolic and histological outcomes, and (3) there are limitations to the laying hen as a model of NAFLD as the pathogenic changes may not adequately match the human condition.

Nonalcoholic fatty liver disease (NAFLD) is categorized into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) and has emerged as a risk factor for more critical clinical conditions. However, the underlying mechanisms of NAFLD pathogenesis are not fully understood. In this study, expression of proteins associated with endoplasmic reticulum (ER) stress, apoptosis and autophagy were analyzed in normal, NAFL and NASH human livers by western blotting. Levels of some ER stress-transducing transcription factors, including cleaved activating transcription factor 6, were higher in NASH than in the normal tissues. However, the expression of a majority of the ER chaperones and foldases analyzed, including glucose-regulated protein 78 and ER protein 44, was lower in NASH than in the normal tissues. Levels of apoptosis markers, such as cleaved poly (ADP-ribose) polymerase, were also lower in NASH tissues, in which expression of some B-cell lymphoma-2 family proteins was up-or down-regulated compared to the normal tissues. The level of the autophagy substrate p62 was not different in NASH and normal tissues, although some autophagy regulators were up-or down-regulated in the NASH tissues compared to the normal tissues. Levels of most of the proteins analyzed in NAFL tissues were either similar to those in one of the other two types, NASH and normal, or were somewhere in between. Together, these findings suggest that regulation of certain important tissues processes involved in protein quality control and cell survival were broadly compromised in the NAFLD tissues.