Applications of magnetic resonance spectroscopy for noninvasive assessment of hepatic steatosis

MR spectroscopy is a noninvasive technique to quantify hepatic steatosis. MR spectroscopy provides information about the chemical composition of tissues in a spectrum. Hepatic steatosis is characterized by accumulation of fat in the liver. The prevalence of hepatic steatosis is increasing due to its relation with obesity and insulin resistance in non-alcoholic fatty liver disease. This thesis describes the applications of MR spectroscopy (primarily on 3T) for noninvasive assessment of hepatic steatosis. Several aspects of MR spectroscopy were studied such as a meta-analysis of literature, reproducibility, comparison of accuracy of available imaging modalities for hepatic steatosis assessment, hepatic steatosis assessment in a cohort of morbidly obese patients, evaluation of hepatic steatosis in an experimental rat model and the feasibility of MR spectroscopy for hepatic lipid composition analysis in rats and patients

Hepatic unsaturated fatty acids in patients with non-alcoholic fatty liver disease assessed by 3.0 T MR spectroscopy

Non-alcoholic fatty liver disease (NAFLD) is related to the metabolic syndrome and obesity. Proton magnetic resonance spectroscopy ((1)H MRS) is a non-invasive technique to assess hepatic triglyceride content (HTGC) and allows assessment of unsaturated fatty acids (UFA). There is increasing evidence that hepatic UFA are associated with the development of NAFLD. Therefore the objective of this study was to assess hepatic UFA in patients with NAFLD using (1)H MRS. We included 26 consecutive patients with deranged liver enzymes, with and without type 2 diabetes mellitus (DM2), suspected for NAFLD. Liver function and metabolic parameters were assessed. (1)H MRS measurements were performed at 3.0T. From the (1)H MR spectra two ratios were calculated: ratio 1 (UFA); unsaturated fatty acid peak vs. reference water peak and ratio 2 (HTGC); total fatty acid peak vs. reference water peak. Twenty-six patients were included. In these patients hepatic UFA (ratio 1) correlated with AST/ALT ratio (r=-0.46, p=0.02), glucose levels (r=0.46, p=0.018), HOMA-IR (r=0.59, p=0.004) and HTGC (r=0.81, p <0.001). In diabetic patients (n=12) hepatic UFA correlated with alkaline phosphatase levels (r=0.72, p=0.01), HOMA-IR (r=0.73, p=0.01) and HTGC (r=0.83, p=0.002). Compared to non-diabetic patients with NAFLD, hepatic UFA levels were increased in patients with DM2 and NAFLD (0.032 vs. 0.014, p=0.03). Hepatic UFA can be assessed with (1)H MRS. (1)H MRS determined hepatic UFA correlate with clinical and metabolic parameters associated with NAFLD. Hepatic UFA are increased in patients with DM2. This study provides evidence for the use of non-invasive (1)H MRS to assess hepatic UFA in viv

The hepatic response to FGF19 is impaired in patients with nonalcoholic fatty liver disease and insulin resistance

Schreuder TC, Marsman HA, Lenicek M, van Werven JR, Nederveen AJ, Jansen PL, Schaap FG. The hepatic response to FGF19 is impaired in patients with nonalcoholic fatty liver disease and insulin resistance. Am J Physiol Gastrointest Liver Physiol 298: G440-G445, 2010. First published January 21, 2010; doi: 10.1152/ajpgi.00322.2009.-Intestinal FGF19 has emerged as a novel endocrine regulator of hepatic bile salt and lipid metabolism. In patients with nonalcoholic fatty liver disease (NAFLD) hepatic lipid metabolism is deranged. A possible role of FGF19 in NAFLD has not been reported yet. In this study, we assessed intestinal FGF19 production and the hepatic response to FGF19 in NAFLD patients with and without insulin resistance [homeostasis model of assessment (HOMA) score >= 2.5 (n = 12) and HOMA score >= 2.5 (n = 8), respectively]. To this end, NAFLD patients received a standardized oral fat challenge. Postprandial excursions of triglycerides, bile salts, and FGF19 were monitored, and plasma levels of a marker for bile salt synthesis (7 alpha-hydroxy-4-cholesten-3-one) were determined. Fasted FGF19 levels were comparable in a control group of healthy volunteers (n = 15) and in NAFLD patients (0.26 +/- 0.28 vs. 0.18 +/- 0.09 ng/ml, respectively, P = 0.94). Postprandial FGF19 levels in both controls and NAFLD patients peaked between 3-4 h and were three times higher than baseline levels. The areas under the postprandial FGF19 curve were similar in controls and in the HOMA score-based NAFLD subgroups. In NAFLD patients with HOMA score = 2.5). This impaired hepatic response to FGF19 may contribute to the dysregulation of lipid homeostasis in NAFL

Hepatic steatosis in morbidly obese patients undergoing gastric bypass surgery: assessment with open-system 1H-MR spectroscopy.

OBJECTIVE: The purpose of this study was to assess, with histopathologic control, the use of open-system 1-T (1)H MR spectroscopy for the evaluation of hepatic steatosis in morbidly obese patients undergoing gastric bypass surgery. SUBJECTS AND METHODS: Patients underwent (1)H MR spectroscopy (MRS) for the assessment of steatosis before and 3 months after surgery. Liver biopsy was performed during surgery. Hepatic steatosis was expressed as the ratio of fat peak area to cumulative water and fat peak areas. Histopathologic percentage of steatosis was graded as none (0-5%), mild (5-33%), moderate (33-66%), or severe (> 66%). The accuracy of (1)H-MRS and Spearman correlation coefficient were calculated. Differences between groups were assessed with the Wilcoxon signed rank and Mann-Whitney tests. RESULTS: The study included 38 patients (median age, 45.5 years; median body mass index, 47.7). Before surgery, median steatosis measured with (1)H-MRS was 5.8%. The accuracy of (1)H-MRS was 89% (32/36), and the (1)H-MRS findings correlated with the histopathologic assessment of steatosis (r = 0.85, p < 0.001). With (1)H-MRS, no steatosis was discriminated from mild steatosis (p = 0.011), mild was discriminated from moderate steatosis (p < 0.001), and moderate was discriminated from severe steatosis (p = 0.021). Three months after surgery, steatosis had decreased to 3.1% (p < 0.001). The prevalence of hepatic steatosis measured with (1)H-MRS decreased from 53% to 32%. CONCLUSION: In the care of morbidly obese patients undergoing assessment of hepatic steatosis and changes in steatosis after gastric bypass surgery, (1)H-MRS with an open 1-T MRI system is feasible. Measurements of hepatic fat with (1)H-MRS are accurate and correlate with clinical and histopathologic results

Cooperative action of NC2 and Mot1p to regulate TATA-binding protein function across the genome

Promoter recognition by TATA-binding protein (TBP) is an essential step in the initiation of RNA polymerase II (pol II) mediated transcription. Genetic and biochemical studies in yeast have shown that Mot1p and NC2 play important roles in inhibiting TBP activity. To understand how TBP activity is regulated in a genome-wide manner, we profiled the binding of TBP, NC2, Mot1p, TFIID, SAGA, and pol II across the yeast genome using chromatin immunoprecipitation (ChIP)–chip for cells in exponential growth and during reprogramming of transcription. We find that TBP, NC2, and Mot1p colocalize at transcriptionally active pol II core promoters. Relative binding of NC2α and Mot1p is higher at TATA promoters, whereas NC2β has a preference for TATA-less promoters. In line with the ChIP–chip data, we isolated a stable TBP–NC2–Mot1p–DNA complex from chromatin extracts. ATP hydrolysis releases NC2 and DNA from the Mot1p–TBP complex. In vivo experiments indicate that promoter dissociation of TBP and NC2 is highly dynamic, which is dependent on Mot1p function. Based on these results, we propose that NC2 and Mot1p cooperate to dynamically restrict TBP activity on transcribed promoters

Accuracy of prediction scores and novel biomarkers for predicting nonalcoholic fatty liver disease in obese children.

BACKGROUND: Accurate prediction scores for liver steatosis are demanded clinicians to noninvasively screen for nonalcoholic fatty liver disease Several prediction scores have been developed, however external lacking. OBJECTIVE: The aim was to determine the diagnostic accuracy of existing prediction scores in severely obese children, to develop a new prediction score using novel biomarkers and to compare these results to performance of ultrasonography. DESIGN AND RESULTS: Liver steatosis was using proton magnetic resonance spectroscopy in 119 severely obese age 14.3 +/- 2.1 years, BMI z-score 3.35 +/- 0.35). Prevalence of 47%. The four existing predictions scores ("NAFLD liver fat score," index," "hepatic steatosis index," and the pediatric prediction score) moderate diagnostic accuracy in this cohort (positive predictive value 61, 61, 69% and negative predictive value (NPV) 77, 69, 68, 75%, new prediction score was built using anthropometry, routine biochemistry novel biomarkers (leptin, adiponectin, TNF-alpha, IL-6, CK-18, FGF-21, adiponutrin polymorphisms). The final model included ALT, HOMA, sex, and This equation (PPV 79% and NPV 80%) did not perform substantially better four other equations and did not outperform ultrasonography for (NPV 82%). CONCLUSION: The conclusion is in severely obese children and adolescents existing prediction scores and the tested novel biomarkers insufficient diagnostic accuracy for diagnosing or excluding NAFLD

Yield of Screening for COVID-19 in Asymptomatic Patients Before Elective or Emergency Surgery Using Chest CT and RT-PCR (SCOUT): Multicenter Study

OBJECTIVE: To determine the yield of preoperative screening for COVID-19 with chest CT and RT-PCR in patients without COVID-19 symptoms. SUMMARY OF BACKGROUND DATA: Many centers are currently screening surgical patients for COVID-19 using either chest CT, RT-PCR or both, due to the risk for worsened surgical outcomes and nosocomial spread. The optimal design and yield of such a strategy are currently unknown. METHODS: This multicenter study included consecutive adult patients without COVID-19 symptoms who underwent preoperative screening using chest CT and RT-PCR before elective or emergency surgery under general anesthesia. RESULTS: A total of 2093 patients without COVID-19 symptoms were included in 14 participating centers; 1224 were screened by CT and RT-PCR and 869 by chest CT only. The positive yield of screening using a combination of chest CT and RT-PCR was 1.5% [95% confidence interval (CI): 0.8-2.1]. Individual yields were 0.7% (95% CI: 0.2-1.1) for chest CT and 1.1% (95% CI: 0.6-1.7) for RT-PCR; the incremental yield of chest CT was 0.4%. In relation to COVID-19 community prevalence, up to approximately 6% positive RT-PCR was found for a daily hospital admission rate &gt;1.5 per 100,000 inhabitants, and around 1.0% for lower prevalence. CONCLUSIONS: One in every 100 patients without COVID-19 symptoms tested positive for SARS-CoV-2 with RT-PCR; this yield increased in conjunction with community prevalence. The added value of chest CT was limited. Preoperative screening allowed us to take adequate precautions for SARS-CoV-2 positive patients in a surgical population, whereas negative patients needed only routine procedures