Early changes in natural killer cell function indicate virologic response to interferon therapy for hepatitis C

Background & Aims: Mathematical modeling of hepatitis C virus (HCV) kinetics indicated that cellular immune responses contribute to interferon (IFN)-induced clearance of HCV. We investigated a potential role of natural killer (NK) cells in this process. Methods: Phenotype and function of blood and liver NK cells were studied during the first 12 weeks of treatment with pegylated IFN-alfa and ribavirin, the time period used to define the early virological response. Results: Within hours of treatment initiation, NK cells of patients that had an early virological response increased expression of activating receptors NKG2D, NKp30, and CD16 and decreased expression of NKG2C and 2B4, along with inhibitory receptors SIGLEC7 and NKG2A, resulting in NK cell activation. NK cell cytotoxicity, measured by degranulation and tumor necrosis factor-related apoptosis-inducing ligand production, peaked after 24 hours (P <.01), concomitant with an increase in alanine aminotransferase levels (P <.05), whereas IFN-γ production decreased within 6 hours and did not recover for more than 4 weeks (P <.05). NK cells from liver biopsies taken 6 hours after treatment initiation had increased numbers of cytotoxic CD16 +NK cells (P <.05) and a trend toward increased production of tumor necrosis factorrelated apoptosis-inducing ligand. Degranulation of peripheral blood NK cells correlated with treatment-induced, first-phase decreases in viral load (P <.05) and remained higher in early virological responders than in nonresponders for weeks. Conclusions: IFN activates NK cells early after treatment is initiated. Their cytotoxic function, in particular, is strongly induced, which correlates to virologic response. Therefore, NK cell activation indicates responsiveness to IFN-αbased treatment and suggests the involvement of the innate immune cells in viral clearance

Intracranial Hemorrhage in Patients with a Left Ventricular Assist Device

BACKGROUND: There is a dearth of literature regarding management and outcomes of patients with a left ventricular assist device (LVAD) for advanced heart failure who develop intracranial hemorrhage (ICH). We conducted a case series from 2 centers highlighting patient outcomes and prognostic factors to help clinicians better understand and care for these high-risk patients. METHODS: A case series from 2 large-volume institutions (defined as large by the Nationwide Inpatient Sample hospital size, i.e., \u3e500 beds both with Departments of Neurosurgery and Advanced Heart Failure-Cardiology) was conducted to clarify the prognosis of patients with an LVAD and ICH. We included patients who were being treated with an LVAD who developed ICH. Patient-specific demographics and data regarding heart failure and intracranial hemorrhage characteristics were collected and analyzed to determine which factors contributed to overall survival. RESULTS: We analyzed 59 unique ICHs in patients being treated with an LVAD for heart failure. Initial Glasgow Coma Scale score, presence of midline shift, and ICH size were factors found to be predictive of mortality. One institution had a sicker patient population including patients with ICH with lower Glasgow Coma Scale score, presence of midline shift, and greater hemorrhage size, which led to overall higher mortality compared with the second institution. CONCLUSIONS: Patients being treated with an LVAD who develop ICH have poor outcomes. Predictive factors for same-admission mortality are lower initial Glasgow Coma Scale score, presence of midline shift, and greater ICH volume

Intracranial Hemorrhage in Patients with a Left Ventricular Assist Device

BACKGROUND: There is a dearth of literature regarding management and outcomes of patients with a left ventricular assist device (LVAD) for advanced heart failure who develop intracranial hemorrhage (ICH). We conducted a case series from 2 centers highlighting patient outcomes and prognostic factors to help clinicians better understand and care for these high-risk patients. METHODS: A case series from 2 large-volume institutions (defined as large by the Nationwide Inpatient Sample hospital size, i.e., \u3e500 beds both with Departments of Neurosurgery and Advanced Heart Failure-Cardiology) was conducted to clarify the prognosis of patients with an LVAD and ICH. We included patients who were being treated with an LVAD who developed ICH. Patient-specific demographics and data regarding heart failure and intracranial hemorrhage characteristics were collected and analyzed to determine which factors contributed to overall survival. RESULTS: We analyzed 59 unique ICHs in patients being treated with an LVAD for heart failure. Initial Glasgow Coma Scale score, presence of midline shift, and ICH size were factors found to be predictive of mortality. One institution had a sicker patient population including patients with ICH with lower Glasgow Coma Scale score, presence of midline shift, and greater hemorrhage size, which led to overall higher mortality compared with the second institution. CONCLUSIONS: Patients being treated with an LVAD who develop ICH have poor outcomes. Predictive factors for same-admission mortality are lower initial Glasgow Coma Scale score, presence of midline shift, and greater ICH volume

Intracranial Hemorrhage in Patients with a Left Ventricular Assist Device

BACKGROUND: There is a dearth of literature regarding management and outcomes of patients with a left ventricular assist device (LVAD) for advanced heart failure who develop intracranial hemorrhage (ICH). We conducted a case series from 2 centers highlighting patient outcomes and prognostic factors to help clinicians better understand and care for these high-risk patients. METHODS: A case series from 2 large-volume institutions (defined as large by the Nationwide Inpatient Sample hospital size, i.e., \u3e500 beds both with Departments of Neurosurgery and Advanced Heart Failure-Cardiology) was conducted to clarify the prognosis of patients with an LVAD and ICH. We included patients who were being treated with an LVAD who developed ICH. Patient-specific demographics and data regarding heart failure and intracranial hemorrhage characteristics were collected and analyzed to determine which factors contributed to overall survival. RESULTS: We analyzed 59 unique ICHs in patients being treated with an LVAD for heart failure. Initial Glasgow Coma Scale score, presence of midline shift, and ICH size were factors found to be predictive of mortality. One institution had a sicker patient population including patients with ICH with lower Glasgow Coma Scale score, presence of midline shift, and greater hemorrhage size, which led to overall higher mortality compared with the second institution. CONCLUSIONS: Patients being treated with an LVAD who develop ICH have poor outcomes. Predictive factors for same-admission mortality are lower initial Glasgow Coma Scale score, presence of midline shift, and greater ICH volume

Early Changes in Natural Killer Cell Function Indicate Virologic Response to Interferon Therapy for Hepatitis C

BACKGROUND & AIMS: Mathematical modeling of hepatitis C virus (HCV) kinetics indicated that the cellular immune response contribute to interferon (IFN)-induced clearance of HCV. We investigated a potential role of natural killer (NK) cells in this process. METHODS: Phenotype and function of blood and liver NK cells were studied during the first 12 weeks of treatment with pegylated IFN-alfa and ribavirin, the time period used to define the early virological response. RESULTS: Within hours of treatment initiation, NK cells of patients that had an early virological response increased expression of the activating receptors NKG2D, NKp30, and CD16; they decreased expression of NKG2C and 2B4, along with the inhibitory receptors SIGLEC7 and NKG2A, resulting in NK cell activation. NK cell cytotoxicity, measured by degranulation and TRAIL production, peaked after 24 h (P<.01), concomitant with an increase in alanine aminotransferase levels (P<.05), whereas IFN-g production decreased within 6 h and did not recover for more than 4 weeks (P<.05). NK cells from liver biopsies taken 6 h after treatment initiation had increased numbers of cytotoxic CD16(+) NK cells (P<.05) and a trend towards increased production of TRAIL. Degranulation of peripheral blood NK cells correlated with the treatment-induced, first phase decreases in viral load (P<.05) and remained higher in early virological responders than in nonresponders for weeks. CONCLUSIONS: IFN activates NK cells early after treatment is initiated. Their cytotoxic function, in particular, is strongly induced, which correlates to the virologic response. Therefore, NK cell activation indicates responsiveness to IFN-g–based treatment and indicates the involvement of the innate immune cells in viral clearance