Factors related to environmental influences on a farm such as increased exposure to bacterial compounds in stables where livestock is kept prevent the development of allergic disorders in children.

Daily doses of OCA, ranging from 10 to 50 mg, significantly reduced levels of ALP, γ-glutamyl transpeptidase, and alanine aminotransferase, compared with placebo, in patients with primary biliary cirrhosis who had inadequate responses to ursodeoxycholic acid. The incidence and severity of pruritus were lowest among patients who received 10 mg/d OCA. Biochemical responses to OCA were maintained in a 12-month open-label extension trial. ClinicalTrials.gov ID: NCT00550862.

BACKGROUND:The prevalence of adiposity in childhood is increasing. Is breast-feeding protective as suggested by cross-sectional studies? OBJECTIVE: In a longitudinal birth cohort study, we tested whether breast-feeding for more than 2 months has preventive effects against overweight and adiposity at 6 y. DESIGN: Of 1314 children representing the catchment areas of six delivery units, 918 could be followed up to the age of 6 y. Height, weight, and skin-fold thickness were measured at regular visits. As the criteria of overweight, obesity, and adiposity in the children, the 90th and the 97th percentiles of BMI and skin-fold values were used. Parents with a BMI at or above the 90th percentile, which was 27 kg/m 2 or more, were considered overweight. Infants bottle-fed from birth or breast-fed for less than 3 months were classified as 'bottle-fed' (BO), and those breast-fed for 3 months and more as 'breast-fed' (BR). Univariate comparisons and logistic regression analysis were performed applying SAS 6.12. The final logistic model consisted of the 480 cases for whom complete data for all variables were available. The potential effect of loss to follow-up was analysed by the Cochran-Mantel-Haenzel test: the outcomes were not significantly influenced by loss to follow-up. RESULTS: At birth BMIs were nearly identical in both groups. By 3 months, BO had significantly higher BMIs and thicker skin folds than BR. From 6 months on, compared to BR, a consistently higher proportion of BO children exceeded the 90th and the 97th percentile of BMI and skin-fold thickness reference values. From the age of 4 y to 5 and 6 y, in BO the prevalence of obesity nearly doubled and tripled, respectively. With only minor changes of obesity prevalence in BR, the difference of BMI and skinfold thickness between groups became statistically significant. Logistic regression analysis revealed that overweight of the mother, maternal smoking during pregnancy, bottle feeding, and low social status remained important risk factors for overweight and adiposity at 6 y of age. CONCLUSION: A maternal BMI of 27, bottle-feeding, maternal smoking during pregnancy, and low social status are risk factors for overweight and adiposity at 6 y of age. Early bottle-feeding brings forward the obesity rebound, predictive of obesity in later life.

Obeticholic acid (OCA), a potent farnesoid X receptor agonist, was studied as monotherapy in an international, randomized, double‐blind, placebo‐controlled phase 2 study in patients with primary biliary cholangitis who were then followed for up to 6 years. The goals of the study were to assess the benefit of OCA in the absence of ursodeoxycholic acid, which is relevant for patients who are intolerant of ursodeoxycholic acid and at higher risk of disease progression. Patients were randomized and dosed with placebo (n = 23), OCA 10 mg (n = 20), or OCA 50 mg (n = 16) given as monotherapy once daily for 3 months (1 randomized patient withdrew prior to dosing). The primary endpoint was the percent change in alkaline phosphatase from baseline to the end of the double‐blind phase of the study. Secondary and exploratory endpoints included change from baseline to month 3/early termination in markers of cholestasis, hepatocellular injury, and farnesoid X receptor activation. Efficacy and safety continue to be monitored through an ongoing 6‐year open‐label extension (N = 28). Alkaline phosphatase was reduced in both OCA groups (median% [Q1, Q3], OCA 10 mg −53.9% [−62.5, −29.3], OCA 50 mg −37.2% [−54.8, −24.6]) compared to placebo (−0.8% [−6.4, 8.7]; P < 0.0001) at the end of the study, with similar reductions observed through 6 years of open‐label extension treatment. OCA improved many secondary and exploratory endpoints (including γ‐glutamyl transpeptidase, alanine aminotransferase, conjugated bilirubin, and immunoglobulin M). Pruritus was the most common adverse event; 15% (OCA 10 mg) and 38% (OCA 50 mg) discontinued due to pruritus. Conclusion: OCA monotherapy significantly improved alkaline phosphatase and other biochemical markers predictive of improved long‐term clinical outcomes. Pruritus increased dose‐dependently with OCA treatment. Biochemical improvements were observed through 6 years of open‐label extension treatment. (Hepatology 2018;67:1890‐1902).

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