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Oxysterol 7a-hydroxylase (CYP7B1) controls the levels of intracellular regulatory oxysterols generated by the "acidic pathway" of cholesterol metabolism. Previously, we demonstrated that an inability to upregulate CYP7B1 in the setting of insulin resistance leads to the accumulation of cholesterol metabolites such as (25R)26-hydroxycholesterol (26HC) that initiate and promote hepatocyte injury; followed by an inflammatory response. The current study demonstrates that dietary coffee improves insulin resistance and restores Cyp7b1 levels in a well-characterized Western diet (WD)-induced nonalcoholic fatty liver disease (NAFLD) mouse model. Ingestion of a WD containing caffeinated (regular) coffee or decaffeinated coffee markedly reduced the serum ALT level and improved insulin resistance. Cyp7b1 mRNA and protein levels were preserved at normal levels in mice fed the coffee containing WD. Additionally, coffee led to upregulated steroid sulfotransferase 2b1 (Sult2b1) mRNA expression. In accordance with the response in these oxysterol metabolic genes, hepatocellular 26HC levels were maintained at physiologically low levels. Moreover, the current study provided evidence that hepatic Cyp7b1 and Sult2b1 responses to insulin signaling can be mediated through a transcriptional factor, hepatocyte nuclear factor (HNF)-4a. We conclude coffee achieves its beneficial effects through the modulation of insulin resistance. Both decaffeinated and caffeinated coffee had beneficial effects, demonstrating caffeine is not fundamental to this effect. The effects of coffee feeding on the insulin-HNF4a-Cyp7b1 signaling pathway, whose dysregulation initiates and contributes to the onset and progression of NASH as triggered by insulin resistance, offer mechanistic insight into approaches for the treatment of NAFLD. [ABSTRACT FROM AUTHOR]

Purpose: The long-term efficacy and safety of infliximab (IFX) in children with ulcerative colitis (UC) have not been well-evaluated. Here, we reviewed the long-term durability and safety of IFX in our single center pediatric cohort with UC. Methods: This retrospective study included 20 children with UC who were administered IFX. Results: For induction, 5 mg/kg IFX was administered at weeks 0, 2, and 6, followed by every 8 weeks for maintenance. The dose and interval of IFX were adjusted depending on clinical decisions. Corticosteroid (CS)-free remission without dose escalation (DE) occurred in 30% and 25% of patients at weeks 30 and 54, respectively. Patients who achieved CS-free remission without DE at week 30 sustained long-term IFX treatment without colectomy. However, one-third of the patients discontinued IFX treatment because of a primary nonresponse, and one-third experienced secondary loss of response (sLOR). IFX durability was higher in patients administered IFX plus azathioprine for >6 months. Four of five patients with very early onset UC had a primary nonresponse. Infusion reactions (IRs) occurred in 10 patients, resulting in discontinuation of IFX in four of these patients. No severe opportunistic infections occurred, except in one patient who developed acute focal bacterial nephritis. Three patients developed psoriasis-like lesions. Conclusion: IFX is relatively safe and effective for children with UC. Clinical remission at week 30 was associated with long-term durability of colectomy-free IFX treatment. However, approximately two-thirds of the patients were unable to continue IFX therapy because of primary nonresponse, sLOR, IRs, and other side effects. [ABSTRACT FROM AUTHOR]

Interferon-based simeprevir therapy showed high efficacy and tolerability in children with genotype 1 hepatitis C virus infection. While direct-acting antivirals (DAAs) therapy are undergoing study in children, this regimen is considered an available therapeutic option for selected patients in countries where DAAs have not yet been approved. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was both to assess the incidence and severity of hepatic involvement in newborns with neonatal asphyxia and to identify factors associated with cholestatic liver disease in this patient group. Methods: Subjects comprised full-term infants (gestational age ³ 36 weeks) with neonatal asphyxia who required treatment and hospitalization at our institution between 2008 and 2013 (ICD-10 codes: P210, P211, and P219). Cholestasis was defined as direct bilirubin levels ³1.5 mg/dL. This study was a retrospective study based on medical records. Results: Cholestasis occurred in 10 of 67 cases (14.9%). Cholestasis was resolved merely by observation in eight of the 10 cases (80%). In these eight cases, the initial Apgar score ranged from 1 to 7 points; age of onset ranged from two to eight days; mechanical ventilation was required in six cases; and intrauterine growth retardation occurred in three cases. Advanced cholestatic liver disease occurred in two of the 10 cases (20%), and these patients required treatment with ursodeoxycholic acid and supplementation of fat-soluble vitamins. In these two cases, the initial Apgar scores were 2 and 6 points, and the onset times were 4 and 6 days after birth. Both patients received mechanical ventilation and experienced central nervous system, renal, and gastrointestinal complications. These patients also had persistent jaundice, and differentiation from extrahepatic etiologies, including biliary atresia and metabolic disease, was required. Conclusion: Cholestasis occurred in about 15% of full-term infants who experienced neonatal asphyxia. Among the infants with post-asphyxial cholestasis, advanced cholestatic liver disease occurred in 3% of patients. These patients required careful observation to differentiate their diagnosis from other liver diseases because post-asphyxial cholestasis is evident several days after birth and becomes persistent. Transient neonatal cholestasis was associated with several contributing factors related to the severity of neonatal distress. [ABSTRACT FROM AUTHOR]