Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease

Serum ferritin (SF) levels are commonly elevated in patients with nonalcoholic fatty liver disease (NAFLD) because of systemic inflammation, increased iron stores, or both. The aim of this study was to examine the relationship between elevated SF and NAFLD severity. Demographic, clinical, histologic, laboratory, and anthropometric data were analyzed in 628 adult patients with NAFLD (age, ≥ 18 years) with biopsy-proven NAFLD and an SF measurement within 6 months of their liver biopsy. A threshold SF >1.5 × upper limit of normal (ULN) (i.e., >300 ng/mL in women and >450 ng/mL in men) was significantly associated with male sex, elevated serum alanine aminotransferase, aspartate aminotransferase, iron, transferrin-iron saturation, iron stain grade, and decreased platelets (P < 0.01). Histologic features of NAFLD were more severe among patients with SF >1.5 × ULN, including steatosis, fibrosis, hepatocellular ballooning, and diagnosis of NASH (P < 0.026). On multiple regression analysis, SF >1.5 × ULN was independently associated with advanced hepatic fibrosis (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.05-2.62; P = 0.028) and increased NAFLD Activity Score (NAS) (OR, 1.99; 95% CI, 1.06-3.75; P = 0.033). CONCLUSIONS: A SF >1.5 × ULN is associated with hepatic iron deposition, a diagnosis of NASH, and worsened histologic activity and is an independent predictor of advanced hepatic fibrosis among patients with NAFLD. Furthermore, elevated SF is independently associated with higher NAS, even among patients without hepatic iron deposition. We conclude that SF is useful to identify NAFLD patients at risk for NASH and advanced fibrosis.     

Twenty-four-hour profiles of plasma glucose, insulin, C-peptide and free fatty acid in subjects with varying degrees of glucose tolerance following short-term, medium-dose prednisone (20 mg/day) treatment: evidence for differing effects on insulin secretion and action

Objective To determine the time course and prandial effects of short‐term, medium‐dose prednisone on 24‐h metabolic patterns under standardized conditions. Context Glucocorticoids (GCs) adversely affect glucose homoeostasis but 24‐h profiles of glucose, insulin, C‐peptide and free fatty acids (FFAs) following short‐term, medium‐dose prednisone treatment in persons with varying degrees of glucose tolerance are not well defined. Design An open‐label cross‐sectional interventional study. Subjects Three groups were prospectively studied: persons with type 2 diabetes (T2DM; n = 7), persons ‘at risk’ for T2DM (AR; n = 8) and persons with normal glucose tolerance (NGT; n = 5). Methods Before and after 3‐day treatment with prednisone 20 mg each morning, subjects underwent 24‐h frequent blood sampling. Eucaloric mixed meals were provided at 08:00, 12:00 and 18:00 h. Insulin/glucose ratio provided an estimate of β‐cell response to meal stimuli. Measurements Plasma glucose, insulin, C‐peptide, haemoglobin A1c and FFA. Results Prednisone induced greater increases in glucose levels from midday (P = 0·001) to midnight (P = 0·02) in the T2DM than the AR and NGT groups. In contrast, insulin (P = 0·03) and C‐peptide (P = 0·04) levels decreased postbreakfast in the T2DM group, whereas no changes in the morning but higher C‐peptide levels (P = 0·03) from midday to midnight were observed in the AR group. In the T2DM group, insulin/glucose ratio decreased postbreakfast (P = 0·04) and increased postdinner (P = 0·03). Fasting glucose, insulin and C‐peptide levels were unchanged in all groups, and FFA levels modestly increased postdinner (P = 0·03) in the NGT group. Conclusion Short‐term, medium‐dose prednisone treatment induces postprandial hyperglycaemia in T2DM and AR predominantly from midday to midnight because of suppression of insulin secretion followed by decreased insulin action that dissipates overnight. Effective treatment of prednisone‐induced hyperglycaemia should target both rapid onset relative insulin deficiency and a less than 24‐h total duration of effect.     

Gonadotrophin secretion pattern in anorchid boys from birth to pubertal age: pathophysiological aspects and diagnostic usefulness

Context The biphasic ontogeny of serum gonadotrophins observed in normal children also exists in girls with gonadal dysgenesis, although with higher levels. However, limited data exist in prepubertal boys with anorchia. Objective To investigate whether the existence of testicular tissue is required for gonadotrophin downregulation in boys. Secondarily, we analysed the prevalence of high gonadotrophins and its diagnostic value to assess the presence or absence of testes in childhood. Study design In a retrospective, semi‐longitudinal study, we compared serum gonadotrophin levels in 35 boys with anorchia aged 0–18 years, in 29 bilaterally cryptorchid boys with abdominal testes and in 236 normal boys. Results In anorchid boys, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were abnormally high in the first months after birth, then decreased progressively. LH decreased more readily than FSH and dropped to normal values in up to 70% of anorchid patients before the usual age of pubertal onset, when both gonadotrophins increased again to very high levels. In cryptorchid boys, FSH was elevated in a significantly (P < 0·0001) lower proportion of cases. Below the age of 6 years, FSH below 2 IU/l ruled out anorchia and LH above 5 IU/l confirmed anorchia with high accuracy. Between 6 and 11 years, FSH or LH levels above 5 IU/l were highly specific for the absence of testes. Conclusions The U‐shaped pattern of serum gonadotrophins observed in normal males from birth to puberty was also found in anorchid boys, but with gonadotrophin levels considerably elevated. Serum gonadotrophin levels may normalize in anorchid boys during late childhood only to rise again at puberty. The presence of testicular tissue results in restrain of gonadotrophin secretion in most patients, even if the testes are cryptorchid.     

Timed non-transferrin bound iron determinations probe the origin of chelatable iron pools during deferiprone regimens and predict chelation response

Background

Plasma non-transferrin bound iron refers to heterogeneous plasma iron species, not bound to transferrin, which appear in conditions of iron overload and ineffective erythropoiesis. The clinical utility of non-transferrin bound iron in predicting complications from iron overload, or response to chelation therapy remains unproven. We undertook carefully timed measurements of non-transferrin bound iron to explore the origin of chelatable iron and to predict clinical response to deferiprone.

Design and Methods

Non-transferrin bound iron levels were determined at baseline and after 1 week of chelation in 32 patients with thalassemia major receiving deferiprone alone, desferrioxamine alone, or a combination of the two chelators. Samples were taken at baseline, following a 2-week washout without chelation, and after 1 week of chelation, this last sample being taken 10 hours after the previous evening dose of deferiprone and, in those receiving desferrioxamine, 24 hours after cessation of the overnight subcutaneous infusion. Absolute or relative non-transferrin bound iron levels were related to transfusional iron loading rates, liver iron concentration, 24-hour urine iron and response to chelation therapy over the subsequent year.

Results

Changes in non-transferrin bound iron at week 1 were correlated positively with baseline liver iron, and inversely with transfusional iron loading rates, with deferiprone-containing regimens but not with desferrioxamine monotherapy. Changes in week 1 non-transferrin bound iron were also directly proportional to the plasma concentration of deferiprone-iron complexes and correlated significantly with urine iron excretion and with changes in liver iron concentration over the next 12 months.

Conclusions

The widely used assay chosen for this study detects both endogenous non-transferrin bound iron and the iron complexes of deferiprone. The week 1 increments reflect chelatable iron derived both from liver stores and from red cell catabolism. These increments correlate with urinary iron excretion and the change in liver iron concentration over the subsequent year thus predicting response to deferiprone-containing chelation regimes. This clinical study was registered at clinical.trials.gov with the number {"type":"clinical-trial","attrs":{"text":"NCT00350662","term_id":"NCT00350662"}}NCT00350662.     

Early detection of left ventricular systolic dysfunction using two-dimensional speckle tracking strain evaluation in healthy subjects after acute alcohol intoxication

Objectives: We evaluated the ability of two-dimensional speckle tracking strain echocardiography to detect left ventricular (LV) systolic dysfunction as compared with LV ejection fraction (EF) in healthy subjects following acute alcohol intoxication. Methods and Results: In total, 25 healthy subjects were investigated using echocardiography 4-6 hours after the onset of alcohol intoxication at a regional festive gathering, and then compared to 23 healthy control subjects without alcohol consumption. Heart rate, blood pressure, blood alcohol level, LV volumes, EF, shortening fraction, E/A ratio, as well as global longitudinal strain (LS) were recorded. Mean blood alcohol level was 1.3 ± 0.3 g.L(-1) . Mean systolic blood pressure and heart rate were slightly increased in the alcohol group compared to controls (147.5 ± 21.8 mmHg vs 127.0 ± 9.9 mmHg, P = 0.003, and 79.7 ± 10.7 bpm vs 70.6 ± 7.6 bpm, P < 0.001, respectively). While there was no significant difference in terms of LVEF (62.9 ± 4.4% vs 64.8 ± 5.9%, P = 0.18) or shortening fraction (34.7 ± 5.9% vs 36.0 ± 4.3%, P = 0.54), global LS was significantly impaired (-17.8 ± 2.0% vs -21.2 ± 1.8%, P < 0.001). In addition, subjects who consumed alcohol had increased LV end-diastolic (108.3 ± 20.1 mL vs 95.5 ± 14.6 mL, P = 0.037) and end-systolic volumes (41.6 ± 11.4 mL vs 33.7 ± 6.9 mL, P = 0.024), along with depressed aortic time-velocity integral (19.9 ± 3.2 mL vs 21.9 ± 2.5 mL, P = 0.034). According to multivariate linear regression analyses, blood alcohol level was the only factor significantly associated with global LS (β=-3.6 ± 1.0, P = 0.005). Conclusion: Alcohol intoxication around festive days induces acute LV contraction abnormalities, which may be detected using global LS by speckle tracking at an earlier stage and more accurately than LVEF decreases.     

Mild cognitive impairment and everyday functioning in older adults

The relations between mild cognitive impairment without dementia (MCI/CIND) and everyday functional abilities were examined using data from the Canadian Study of Health and Aging (CSHA). Individuals were identified with MCI/CIND if both caregiver report and clinician judgment agreed on the presence of cognitive impairment in the absence of dementia. Cross-sectional and longitudinal comparisons indicated that individuals with MCI/CIND demonstrated a broad range of impairment in instrumental activities of daily living (IADL) compared to individuals with no cognitive impairment (NCI). In cross-sectional analyses, neuropsychological measures of memory and psychomotor speed were significantly related to impairment in eight areas of functioning. In addition, poorer memory performance was significantly predictive of future impairment in money management.