Biliary atresia is a devastating biliary disease of neonates that results in liver transplantation for the vast majority. The etiology of biliary atresia is unknown and is likely multifactorial, with components of genetic predisposition, environmental trigger and autoimmunity contributing to disease pathogenesis. This review highlights recent work related to investigations of disease pathogenesis in biliary atresia.

Chronic hepatitis C virus (HCV) infection is characterized by dysregulated natural killer (NK) cell responses. NKs play a critical role in achieving sustained responses to interferon (IFN)‐α‐based therapy. Rapid sustained HCV‐RNA clearance is now achieved with direct‐acting antivirals (DAAs). Studies of patients receiving first‐wave DAAs suggest NK functional restoration. Here, we investigate the effect of mainstream DAA treatment on NKs. We collected a prospective cohort of male HCV genotype 1‐infected patients treated with ledipasvir/sofosbuvir (n = 22). Peripheral blood was obtained at treatment start, week 2 (W2), W4, W8, and W12 of treatment and 12 weeks posttreatment. Flow cytometry was used to characterize NK responses to therapy. Mean baseline viral load was 1.75 million IU/mL. All subjects rapidly cleared virus and remained HCV RNA‐negative posttreatment. No change was seen in total NK levels; however, the frequency of immature NKs (clusters of differentiation [CD]56bright) decreased by W2 and was maintained throughout the study. Phenotypic changes were evident by W2/W4, coincident with rapid viral clearance. At W2, T‐cell immunoglobulin and mucin‐domain containing‐3 and CD161 were significantly increased, returning to pretreatment levels by W12. Some changes were not evident until late (W12 or posttreatment). Down‐regulation of several activation markers, including NKp30 and tumor necrosis factor–related apoptosis‐inducing ligand, was observed at W12 and sustained posttreatment. No difference was observed in IFN‐γ production or cytokine‐mediated killing of NK‐sensitive cell line K562 posttreatment compared to pretreatment. Conclusion: Our phenotype data suggest transient activation followed by dampening of NK cell activity to pretreatment levels. The NK response to ledipasvir/sofosbuvir is not universal in a homogeneous patient cohort. More studies are needed to elucidate the roles of NK cells in IFN‐free regimens, which will have implications for protection from re‐infection and fibrosis progression. (Hepatology Communications 2018;2:364‐375)

The plasma vasopressin response to intravenous nicotine (2 mg) and smoking cigarettes of high (1.2 mg) and low (0.6 mg) nicotine content was studied in healthy young subjects with a history of cigarette smoking. Nicotine administered intravenously had no effect on plasma vasopressin. There was a statistically significant increase in plasma vasopressin after both the low and high content cigarettes, with the high content cigarettes resulting in a significantly greater increase. All three interventions resulted in transient increases in blood pressure and pulse of similar magnitude. These studies indicate that cigarette smoking-induced vasopressin release is not mediated via an action of circulating nicotine, and suggest the presence of an airway-specific mechanism for vasopressin release.

Significantly larger quantities of alkyldiacylglycerols have been detected in a variety of tumors of animals and man than in healthy tissues from the same sources (1, 2). This is explained by an increased activity of synthesizing enzymes (3) and a decreased activity of a key cleavage enzyme (4) for the ether-linked lipids; both enzymes are found in the microsomal fraction of tumor cells. However, the function of etherlinked lipids in tumors and other mammalian tissues is still not known. Also measurements of alkylglycerolipids in tissues during oncogenesis have not been done.In the experiments described in this paper we have measured the quantity of alkyldiacylglycerols and certain other lipids in the thymus at 3 days after irradiation, when maximum thymic involution occurs, and in thymic leukemia developed in the thymus at 5 mo after irradiation. Our results show that lipid composition is altered in the leukemic thymus and indicate that lipid changes in the irradiated thymus before histologic recognition of thymic leukemia could be important in understanding early events that occur during oncogenesis.Materials and Methods. Irradiation. Inbred 4to 5-wk-old male C57BL/6J mice (Jackson Laboratories, Bar Harbor, ME) received four weekly doses of 200 rads gamma radia-

Feeding difficulties due to functional gastrointestinal (GI) symptoms (i.e., nausea, pain, and bloating) are well described in patients with hypermobile-type Ehlers-Danlos Syndrome. These symptoms are particularly difficult to treat when there is comorbid dysautonomia, usually manifesting as postural orthostatic tachycardia syndrome. Here, we describe a successful trial of multidisciplinary rehabilitative interventions to avoid placement of a surgical feeding tube in such a patient. Main components of intervention were intensive pelvic floor physiotherapy and biofeedback, occupational therapy focused on coping with feeding-related symptoms, psychology support, and medications targeting histamine blockade and enhancing intestinal motility.

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