Direct hyperbilirubinemia in newborns with gastroschisis.

BACKGROUND: Patients with gastroschisis and prolonged total (or partial) parenteral nutrition (PN) commonly develop direct hyperbilirubinemia (DH). OBJECTIVE: To quantify the prevalence and severity of DH in newborns with gastroschisis and characterize the diagnostic work-up for DH in this patient population. DESIGN/METHODS: Retrospective chart review of patients born with gastroschisis between 2005 and 2015 for the first 6 months of life. RESULTS: 29 patients were identified with gastroschisis. Mean gestational age and birthweight were 36.4 (± 1.8) weeks and 2.5 (± 0.6) kg. 41% were treated with primary reduction versus staged closure. Peak total and direct bilirubin (DB) levels were 10.17 ± 6.21 mg/dL and 5.58 ± 3.94 mg/dL, respectively. 23 patients (79.3%) were diagnosed with DH and 78.2% underwent additional work-up for hyperbilirubinemia consisting of imaging and laboratory studies, none of which revealed a cause for DH other than the presumed PN-associated cholestasis. In all patients, DB began to decline within 1-10 days of initiation of enteral feeds. CONCLUSION(S): DH is common in patients with gastroschisis and is unlikely to be associated with pathology aside from PN. Additional work-up may lead to unnecessary resource utilization. LEVELS OF EVIDENCE: Case series with no comparison group, Level IV.

Characterization of the Specificity, Functionality, and Durability of Host T-Cell Responses Against the Full-Length Hepatitis E Virus.

The interplay between host antiviral immunity and immunopathology during hepatitis E virus (HEV) infection determines important clinical outcomes. We characterized the specificity, functionality, and durability of host T-cell responses against the full-length HEV virus and assessed a novel "Quantiferon" assay for the rapid diagnosis of HEV infection. Eighty-nine volunteers were recruited from Oxford, Truro (UK), and Toulouse (France), including 44 immune-competent patients with acute HEV infection, 18 HEV-exposed immunosuppressed organ-transplant recipients (8 with chronic HEV), and 27 healthy volunteers. A genotype 3a peptide library (616 overlapping peptides spanning open reading frames [ORFs] 1-3) was used in interferon-gamma (IFN-γ) T-cell ELISpot assays. CD4+ /CD8+ T-cell subsets and polyfunctionality were defined using ICCS and SPICE analysis. Quantification of IFN-γ used whole-blood stimulation with recombinant HEV-capsid protein in the QuantiFERON kit. HEV-specific T-cell responses were detected in 41/44 immune-competent HEV exposed volunteers (median magnitude: 397 spot-forming units/106 peripheral blood mononuclear cells), most frequently targeting ORF2. High-magnitude, polyfunctional CD4 and CD8+ T cells were detected during acute disease and maintained to 12 years, but these declined over time, with CD8+ responses becoming more monofunctional. Low-level responses were detectable in immunosuppressed patients. Twenty-three novel HEV CD4+ and CD8+ T-cell targets were mapped predominantly to conserved genomic regions. QuantiFERON testing demonstrated an inverse correlation between IFN-γ production and the time from clinical presentation, providing 100% specificity, and 71% sensitivity (area under the receiver operator characteristic curve of 0.86) for HEV exposure at 0.3 IU/mL. CONCLUSION: Robust HEV-specific T-cell responses generated during acute disease predominantly target ORF2, but decline in magnitude and polyfunctionality over time. Defining HEV T-cell targets will be important for the investigation of HEV-associated autoimmune disease. (Hepatology 2016;64:1934-1950).

The management of low-risk primary upper gastrointestinal haemorrhage in the community: a 5-year observational study.

BACKGROUND: Acute upper gastrointestinal haemorrhage is a common medical emergency, initially managed with inpatient care. Bleeding stops spontaneously in over 80% of cases, indicating that patients with low-risk upper gastrointestinal haemorrhage may be more optimally managed in the community, without the need for admission to hospital. AIM: To assess the safety of managing patients with low-risk upper gastrointestinal haemorrhage without admission to hospital. METHODS: Prospective/retrospective study of all patients presenting to a UK teaching hospital with low-risk upper gastrointestinal haemorrhage who were managed without admission to hospital over 5 years. Low risk was defined as Glasgow Blatchford Score of 2 or less, age below 70 years, no other active medical problems, not taking warfarin and suspected nonvariceal bleed. Outcome measures were the need for intervention (blood transfusion, endoscopic therapy or surgery) and death. RESULTS: One hundred and forty-two patients fulfilled the inclusion criteria, and were managed without admission to hospital. No patients required endoscopic intervention, blood transfusion or surgery. The 28-day mortality was nil. Forty-one patients had normal endoscopic examination and 11 had significant endoscopic findings (peptic ulceration=10, oozing Mallory-Weiss tear=1) but did not require intervention. CONCLUSION: Patients presenting with a primary upper gastrointestinal haemorrhage aged below 70 years with a Glasgow Blatchford Score of 2 or less are at a low risk, and can be safely managed in the community.

Host risk factors and autochthonous hepatitis E infection.

INTRODUCTION: In developed countries autochthonous hepatitis E infection is caused by hepatitis E virus (HEV) genotype 3 or 4 and mainly affects middle aged/elderly men. Host factors might explain why older men develop clinically overt disease. METHODS: Retrospective review of 53 patients with symptomatic autochthonous hepatitis E infection to determine putative host risk factors. Patients were compared with 564 controls with adjustment for age and sex. Anti-HEV seroprevalence was determined in controls and 189 patients with chronic liver disease. RESULTS: Mean age of the patients was 62.4 years, 73.6% were men. Compared with controls, patients with hepatitis E were more likely to drink at least 22 U alcohol/week (OR=9.4; 95% confidence interval=3.8-25.0; P<0.001). The seroprevalence of anti-HEV IgG in controls increased with age (P<0.001) but was similar in men and women. There was no association between alcohol consumption and anti-HEV IgG seroprevalence in the control group. There was no difference in the anti-HEV IgG seroprevalence between the controls and patients with chronic liver disease of all aetiologies, but seroprevalence was higher in controls (13.8%) than patients with alcoholic liver disease (4.8%, P=0.04). CONCLUSION: Clinically apparent hepatitis E infection is more common in individuals who consume at least 22 U alcohol/week. Patients with established chronic alcoholic liver disease have a low seroprevalence compared with controls. The reason for this observation is uncertain, but patients with alcoholic liver disease have clinically severe disease with a high mortality when exposed to HEV. The low seroprevalence in this group may represent a 'culled' population.