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We assessed the performance of magnetic resonance imaging (MRI) proton density fat fraction (PDFF) in children to stratify hepatic steatosis grade before and after treatment in the Cysteamine Bitartrate Delayed-Release for the Treatment of Nonalcoholic Fatty Liver Disease in Children (CyNCh) trial, using centrally scored histology as reference. Participants had multiecho 1.5 Tesla (T) or 3T MRI on scanners from three manufacturers. Of 169 enrolled children, 110 (65%) and 83 (49%) had MRI and liver biopsy at baseline and at end of treatment (EOT; 52 weeks), respectively. At baseline, 17% (19 of 110), 28% (31 of 110), and 55% (60 of 110) of liver biopsies showed grades 1, 2, and 3 histological steatosis; corresponding PDFF (mean±SD) values were 10.9±4.1%, 18.4±6.2%, and 25.7±9.7%, respectively. PDFF classified grade 1 versus 2-3 and 1-2 versus 3 steatosis with areas under receiving operator characteristic curves (AUROCs) of 0.87 (95% confidence interval [CI], 0.80, 0.94) and 0.79 (0.70, 0.87), respectively. PDFF cutoffs at 90% specificity were 17.5% for grades 2-3 steatosis and 23.3% for grade 3 steatosis. At EOT, 47% (39 of 83), 41% (34 of 83), and 12% (10 of 83) of biopsies showed improved, unchanged, and worsened steatosis grade, respectively, with corresponding PDFF (mean±SD) changes of -7.8±6.3%, -1.2±7.8%, and 4.9±5.0%, respectively. PDFF change classified steatosis grade improvement and worsening with AUROCs (95% CIs) of 0.76 (0.66, 0.87) and 0.83 (0.73, 0.92), respectively. PDFF change cut-off values at 90% specificity were -11.0% and +5.5% for improvement and worsening.ConclusionMRI-estimated PDFF has high diagnostic accuracy to both classify and predict histological steatosis grade and change in histological steatosis grade in children with NAFLD. (Hepatology 2018;67:858-872).

A hypo-estrogenic status, as that occurring with menopause, has been proposed to negatively affect cognitive function in post-menopause women. Nevertheless, little is known about the improvement of cognitive functions during antidepressant treatment in post-menopausal women with major depressive disorder (MDD) and its relation with hormonal changes. Hence, this study aimed to investigate the role of menopausal status including the level of sex hormones on cognitive function during antidepressant treatment.Thirty-nine female patients (n=17 in pre-menopause; n=22 in post-menopause) with MDD based on DSM-IV criteria and who were not on hormonal replacement therapies participated in a prospective, 6-week, open-label naturalistic study. All patients were recruited in a university-based hospital. The Hamilton rating scale for Depression (HAMD), Montgomery-Asberg Depression Rating Scale (MADRS) and the Cognitive Failure Questionnaire (CFQ) were administered at baseline, week 1, week 3, and week 6. Levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) were collected at baseline visit.Cognitive functioning improved during antidepressant treatment in the overall sample (P=0.00001). In post-menopausal women, E2 levels were strongly correlated with CFQ scores at each measurement. After controlling for depression severity, E2 levels maintained a significant association with the baseline CFQ scores (regression analysis: beta= -0.55 P=0.010; correlation: R= -0.54). In addition, the reduction of CFQ scores during antidepressant treatment was significantly associated with E2 levels (P=0.021), independently from the improvement of depressive symptoms, which however had a strong effect (P=0.0003). Nevertheless, we failed to find any association of CFQ score with sex hormones in pre-menopausal women.In post-menopausal women, the CFQ scores were correlated with E2 levels and the reduction of CFQ score during antidepressant treatment was also dependent on E2 levels, even controlling for depressive symptoms severity.The present study further supports a crucial role of E2 on the cognitive function in post-menopause women. Moreover, our results suggest that E2 may influence the improvement of cognitive function in post-menopause women with MDD, during treatment with antidepressants.

Depression affects 7% of the elderly population, and it often remains misdiagnosed or untreated. Peripheral biomarkers might aid clinicians by allowing more accurate and well-timed recognition of the disease. We sought to determine if plasma protein levels predict the severity of depressive symptomatology or distinguish patients from healthy individuals. The severity of depressive symptoms and global cognitive functioning were assessed by the Geriatric Depression Scale (GDS) and Mini-Mental State Examination (MMSE) in 152 elderly subjects, 76 of which with major depressive disorder (MDD). Plasma levels of 24 proteins were measured by multiplexing and analyzed as continuous predictors or dichotomized using the median value. The association between individual plasma proteins and MDD risk or depressive symptoms severity was investigated using multiple logistic and linear regressions including relevant covariates. Sensitivity analyses were performed excluding cognitively impaired individuals or non-acute patients with MDD. After adjusting for possible confounders and false discovery rate (FDR) correction, we found lower Fetuin-A levels in MDD patients vs. controls (pFDR = 1.95 × 10–6). This result was confirmed by the sensitivity and dichotomized analyses. Lower prolactin (PRL) levels predicted more severe depressive symptoms in acute MDD patients (pFDR = 0.024). Fetuin-A is a promising biomarker of MDD in the elderly as this protein was negatively associated with the disorder in our sample, regardless of the global cognitive functioning. Lower PRL levels may be a peripheral signature of impaired neuroprotective processes and serotoninergic neurotransmission in more severely depressed patients.