The Utility and Diagnostic Accuracy of Transient Elastography in Adults with Morbid Obesity: A Prospective Study.

Patients with morbid obesity are at high risk for nonalcoholic fatty liver disease (NAFLD) complicated by liver fibrosis. The clinical utility of transient elastography (TE) by Fibroscan in patients with morbid obesity (body mass index (BMI) ≥ 40 kg/m2) is not well-defined. We examined the diagnostic accuracy of Fibroscan in predicting significant liver fibrosis (fibrosis stage ≥2) in morbidly obese patients (BMI ≥ 40 kg/m2). Patients scheduled for bariatric surgery were prospectively enrolled. Intraoperative liver biopsy, liver-stiffness measurement (LSM) by Fibroscan (XL probe), and biochemical evaluation were all performed on the same day. The endpoint was significant liver fibrosis defined as fibrosis stage ≥2 based on the Nonalcoholic Steatohepatitis Clinical Research Network. The optimal LSM cutoff value for detecting significant fibrosis was determined by using the Youden Index method. Routine clinical, laboratory, and elastography data were analyzed by stepwise logistic regression analysis to identify predictors of significant liver fibrosis and build a predictive model. An optimal cutoff point of the new model's regression formula for predicting significant fibrosis was determined by using the Youden index method. One hundred sixty-seven patients (mean age, 46.4 years) were included, of whom 83.2% were female. Histological assessment revealed the prevalence of steatohepatitis and significant fibrosis of 40.7% and 11.4%, respectively. The median LSM was found to be significantly higher in the significant fibrosis group compared to those in the no or non-significant fibrosis group (18.2 vs. 7.7 kPa, respectively; p = 0.0004). The optimal LSM cutoff for predicting significant fibrosis was 12.8 kPa, with an accuracy of 71.3%, sensitivity of 73.7%, specificity of 70.9%, positive predictive value of 24.6%, negative predictive value of 95.5%, and ROC area of 0.723 (95% CI: 0.62-0.83). Logistic regression analysis identified three independent predictors of significant fibrosis: LSM, hemoglobin A1c, and alkaline phosphatase. A risk score was developed by using these three variables. At an optimal cutoff value of the regression formula, the risk score had an accuracy of 79.6% for predicting significant fibrosis, sensitivity of 89.5%, specificity of 78.4%, positive predictive value of 34.7%, negative predictive value of 98.3%, and ROC area of 0.855 (95% CI: 0.76-0.95). Fibroscan utility in predicting significant liver fibrosis in morbidly obese subjects is limited with accuracy of 71.3%. A model incorporating hemoglobin A1c and alkaline phosphatase with LSM improves accuracy in detecting significant fibrosis in this patient population.

Compromised hepatic mitochondrial fatty acid oxidation and reduced markers of mitochondrial turnover in human NAFLD.

BACKGROUND AND AIMS: NAFLD and its more-advanced form, steatohepatitis (NASH), is associated with obesity and is an independent risk factor for cardiovascular, liver-related, and all-cause mortality. Available human data examining hepatic mitochondrial fatty acid oxidation (FAO) and hepatic mitochondrial turnover in NAFLD and NASH are scant. APPROACH AND RESULTS: To investigate this relationship, liver biopsies were obtained from patients with obesity undergoing bariatric surgery and data clustered into four groups based on hepatic histopathological classification: Control (CTRL; no disease); NAFL (steatosis only); Borderline-NASH (steatosis with lobular inflammation or hepatocellular ballooning); and Definite-NASH (D-NASH; steatosis, lobular inflammation, and hepatocellular ballooning). Hepatic mitochondrial complete FAO to CO2 and the rate-limiting enzyme in ß-oxidation (ß-hydroxyacyl-CoA dehydrogenase activity) were reduced by ~40%-50% with D-NASH compared with CTRL. This corresponded with increased hepatic mitochondrial reactive oxygen species production, as well as dramatic reductions in markers of mitochondrial biogenesis, autophagy, mitophagy, fission, and fusion in NAFL and NASH. CONCLUSIONS: These findings suggest that compromised hepatic FAO and mitochondrial turnover are intimately linked to increasing NAFLD severity in patients with obesity.

A Model Incorporating Serum Alkaline Phosphatase for Prediction of Liver Fibrosis in Adults with Obesity and Nonalcoholic Fatty Liver Disease.

We assessed the relationship between serum alkaline phosphatase (ALP) and liver fibrosis by histology, in addition to other noninvasive parameters, in obese patients undergoing metabolic surgery. Patients scheduled for elective bariatric surgery were prospectively recruited from a bariatric clinic. An intraoperative liver biopsy was performed, and liver histology was evaluated by a pathologist blinded to the patients' data. The endpoint was significant fibrosis defined as fibrosis stage ≥ 2. Independent predictors of fibrosis were identified by logistic regression. Two hundred ten patients were recruited. Liver histology revealed steatosis in 87.1%, steatohepatitis in 21.9%, and significant fibrosis in 10%. Independent predictors of significant fibrosis were ALP (Odds Ratio (OR) 1.03; 95% Confidence interval (CI), 1.01-1.05), alanine aminotransferase (OR 1.02; 95% CI, 1.01-1.03), HbA1c (OR 1.58; 95% CI, 1.20-2.09), and body mass index (OR 1.06; 95% CI, 1.00-1.13). A tree-based model was developed to predict significant fibrosis, with a receiver operating characteristic (ROC) area of 0.845, sensitivity of 0.857, specificity of 0.836, and accuracy of 0.931. The applicability of serum ALP as an independent biomarker of liver fibrosis should be considered in obesity surgery patients, and in the broader context of obese patients with nonalcoholic fatty liver disease.

Improving compliance with guidelines for hypertensive disorders of pregnancy through an electronic health record alert: A retrospective chart review.

OBJECTIVES: Improve appropriate and timely administration of rapid acting antihypertensive medication for the management of hypertensive emergency in pregnancy with utilization of an automated electronic health record (EHR) alert in an academic birthplace. STUDY DESIGN: An automated alert was incorporated into an existing EHR that notified providers of a documented severe range blood pressure, defined as systolic blood pressure (SBP) ≥ 160 mmHg or diastolic blood pressure (DBP) ≥ 110 mmHg. Retrospective chart review was utilized to evaluate appropriate intervention before and after implementation of the alert (referred to as pre-implementation and post-implementation cohorts). MAIN OUTCOME MEASURES: The primary outcome was appropriate administration of rapid-acting antihypertensive medication for the management of hypertensive emergency. Secondary outcomes included: appropriate administration of intravenous (IV) magnesium sulfate for seizure prophylaxis, initiation of oral antihypertensive medication postpartum, and appropriate timing of follow up for blood pressure evaluation following discharge. RESULTS: Of 98 patients identified as having hypertensive emergency in the pre-implementation cohort, 34 (35%) received treatment with a rapid acting antihypertensive medication within one hour compared with 54 of 104 (55%) of patients in the post-implementation cohort (35% vs 55%, RR 1.40 95% CI 1.07-1.82). Significantly more patients followed up for a blood pressure check within one week of discharge (41% vs 31%; p = 0.02). There was not a significant effect on the administration of IV magnesium sulfate or initiation of oral medications postpartum. CONCLUSION: An automated EHR alert improved timely administration of rapid-acting antihypertensive medications for hypertensive emergency and has the potential to improve compliance with national preeclampsia guidelines.

Deficiency of MGAT2 increases energy expenditure without high-fat feeding and protects genetically obese mice from excessive weight gain.

Acyl CoA:monoacylglycerol acyltransferase 2 (MGAT2) is thought to be crucial for dietary fat absorption. Indeed, mice lacking the enzyme (Mogat2(-/-)) are resistant to obesity and other metabolic disorders induced by high-fat feeding. However, these mice absorb normal quantities of fat. To explore whether a high level of dietary fat is an essential part of the underlying mechanism(s), we examined metabolic responses of Mogat2(-/-) mice to diets containing varying levels of fat. Mogat2(-/-) mice exhibited 10-15% increases in energy expenditure compared with wild-type littermates; although high levels of dietary fat exacerbated the effect, this phenotype was expressed even on a fat-free diet. When deprived of food, Mogat2(-/-) mice expended energy and lost weight like wild-type controls. To determine whether MGAT2 deficiency protects against obesity in the absence of high-fat feeding, we crossed Mogat2(-/-) mice with genetically obese Agouti mice. MGAT2 deficiency increased energy expenditure and prevented these mice from gaining excess weight. Our results suggest that MGAT2 modulates energy expenditure through multiple mechanisms, including one independent of dietary fat; these findings also raise the prospect of inhibiting MGAT2 as a strategy for combating obesity and related metabolic disorders resulting from excessive calorie intake.