Genome-wide association studies have identified 32 loci associated with body mass index (BMI), a measure that does not allow distinguishing lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ~2.5 million SNPs and body fat percentage from 36,626 individuals, and followed up the 14 most significant (P<10−6) independent loci in 39,576 individuals. We confirmed the previously established adiposity locus in FTO (P=3×10−26), and identified two new loci associated with body fat percentage, one near IRS1 (P=4×10−11) and one near SPRY2 (P=3×10−8). Both loci harbour genes with a potential link to adipocyte physiology, of which the locus near IRS1 shows an intriguing association pattern. The body-fat-decreasing allele associates with decreased IRS1 expression and with an impaired metabolic profile, including decreased subcutaneous-to-visceral fat ratio, increased insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease, and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance.

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Drug-induced liver injury (DILI) patients who do not resolve their liver damage during the first year should be considered chronic DILI patients. Risk factors for DILI chronicity are older age, dyslipidemia and severity of the acute episode. Chronic DILI is not a very common condition; normally featuring mild liver profile abnormalities and not being an important clinical problem, with the exception of a small number of cases of early onset cirrhosis.

From these studies, we conclude that liver transplantation remains the therapeutic choice for fulminant hepatic failure in children. Early referral and closer follow-up is necessary for timely admission to liver transplant centers to enable screening and proper preparation of these patients for liver transplantation.

BackgroundAnimal studies have shown the reproductive toxicity of a number of heavy metals. Very few human observational studies have analyzed the relationship between male reproductive function and heavy metal concentrations in diverse biological fluids.MethodsThe current study assessed the associations between seminal and hormonal parameters and the concentration of the 3 most frequent heavy metal toxicants (lead, cadmium and mercury) in three different body fluids. Sixty one men attending infertility clinics that participated in a case-control study to explore the role of environmental toxins and lifestyles on male infertility were analyzed. Concentration of lead, cadmium and mercury were measured in blood and seminal plasma and whole blood using anodic stripping voltammetry and atomic absorption spectrophotometry. Serum samples were analyzed for follicle-stimulating hormone, luteinizing hormone and testosterone. Semen analyses were performed according to World Health Organization criteria. Mann-Whitney test and Spearman's rank correlations were used for unadjusted analyses. Multiple linear regression models were performed controlling for age, body mass index and number of cigarettes per day.ResultsThere were no significant differences between cases and controls in the concentrations of heavy metals in any of the three body fluids. In multivariate analyses using all subjects no significant associations were found between serum hormone levels and metal concentrations. However there was a significant positive association between the percentage of immotile sperms and seminal plasma levels of lead and cadmium.ConclusionsOur results suggest that the presence of lead and cadmium in the reproductive tract of men may be related to a moderate alteration of their seminal parameters.

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The LIS2T study was an open-label, multicenter study in which recipients of a primary liver transplant were randomized to cyclosporine microemulsion (CsA-ME) (Neoral) (n ϭ 250) (monitoring of blood concentration at 2 hours postdose) C 2 or tacrolimus (n ϭ 245) (monitoring of trough drug blood level [predose]) C 0 to compare efficacy and safety at 3 and 6 months and to evaluate patient status at 12 months. All patients received steroids with or without azathioprine. At 12 months, 85% of CsA-ME patients and 86% of tacrolimus patients survived with a functioning graft (P not significant). Efficacy was similar in deceased-and living-donor recipients. Significantly fewer hepatitis C-positive patients died or lost their graft by 12 months with CsA-ME (5/88, 6%) than with tacrolimus (14/85, 16%) (P Ͻ 0.03). Recurrence of hepatitis C virus in liver grafts was similar in each group. Based on biopsies driven by clinical events, the mean time to histological diagnosis of hepatitis C virus recurrence was significantly longer with CsA-ME (100 Ϯ 50 days) than with tacrolimus (70 Ϯ 40 days) (P Ͻ 0.05). Median serum creatinine at 12 months was 106 mol/L with CsA-ME and with tacrolimus. More patients who were nondiabetic at baseline received antihyperglycemic therapy in the tacrolimus group at 12 months (13% vs. 5%, P Ͻ 0.01). Of patients who were diabetic at baseline, more tacrolimus-treated individuals required anti-diabetic treatment at 12 months (70% vs. 49%, P ϭ 0.02). Treatment for de novo or preexisting hypertension or hyperlipidemia was similar in both groups. In conclusion, the efficacy of CsA-ME monitored by blood concentration at 2 hours postdose and tacrolimus in liver transplant patients is equivalent to 12 months, and renal function is similar. More patients required antidiabetic therapy with tacrolimus regardless of diabetic status at baseline. Abbreviations: CsA-ME, cyclosporine microemulsion; CsA, cyclosporine; C 2, blood concentration at 2 hours postdose; HCV, hepatitis C virus; C 0, trough drug blood level (predose).

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