BACKGROUND & AIMS Chronic hepatitis C virus infection activates an intrahepatic immune response, leading to increased expression of interferon (IFN)-stimulated genes and activation of natural killer (NK) cells—the most prevalent innate immune cell in the liver. We investigated whether the elimination of HCV with direct-acting antiviral agents normalizes expression of IFN-stimulated genes and NK cell function. METHODS We used multicolor flow cytometry to analyze NK cells from liver and blood of 13 HCV-infected patients who did not respond to treatment with pegylated interferon and ribavirin. Samples were collected before and during IFN-free treatment with daclatasvir and asunaprevir therapy and compared with those from blood of 13 healthy individuals (controls). Serum levels of CXCL10 and CXCL11 were measured by ELISA. RESULTS Before treatment, all patients had increased levels of CXCL10 or CXCL11 and a different NK cell phenotype from controls, characterized by increased expression of HLA-DR, NKp46, NKG2A, CD85j, pSTAT1, STAT1, and TNF-related apoptosis-inducing ligand (TRAIL). NK cells from patients also had increased degranulation and decreased production of IFNγ and TNFα compared with NK cells from controls. Nine patients had an end-of-treatment response (undetectable virus) and 4 had virologic breakthrough between weeks 4 and 12 of therapy. A rapid decrease in viremia and level of inflammatory cytokines in all patients was associated with decreased activation of intrahepatic and blood NK cells; it was followed by restoration of a normal NK cell phenotype and function by week 8 in patients with undetectable viremia. This normalized NK cell phenotype was maintained until week 24 (EOT). CONCLUSIONS DAA-mediated clearance of HCV is associated with loss of intrahepatic immune activation by IFNα, indicated by decreased levels of CXCL10 and CXCL11 and normalization of NK cell phenotype and function.

NCT01888900 and NCT00718172.

Background and Objectives: Interprofessional education is a critical component of medical student training, yet it is often difficult to implement. Medical students who learn with, from, and about learners from other disciplines have been shown to create more effective and safe health care teams. The investigators wanted to know how participating in two interprofessional observed structured clinical exams (OSCEs) at Tufts University School of Medicine (TUSM) would affect changes in medical students’ attitudes and values in interprofessional teamwork. Methods: For the academic years 2017 and 2018, two interprofessional case scenarios were integrated into OSCEs for third-year medical students at TUSM, with an allied embedded actor (AEA) playing a social worker to an end-of-life scenario, and an AEA playing the role of a pharmacy student added to a chronic pain scenario. Students participated in didactic training about interprofessional teamwork and received structured feedback regarding interprofessional competencies following simulation cases. Changes in interprofessional knowledge and attitudes were assessed by comparing student pre- and postscenario mean scores on the Interprofessional Socialization and Valuing Scale (ISVS-21, a 21-item scale survey), with students rating themselves on a Likert scale from 1 (not at all) to 7 (to a very great extent). We performed paired t-test analysis on individual pre- and post-ISVS-21 means. Results: Three hundred fifty-three of the 417 participating medical students fully completed pre- and postsurveys. Students reported significant changes in interprofessional knowledge and attitudes (mean change=1.3, P<.0001). Students and faculty regarded the interprofessional cases very highly. Conclusions: Placing interprofessional cases involving AEAs into OSCE events is easily replicated, and positively impacts students’ attitudes and values in interprofessional knowledge.