Effects of Hepatitis B Surface Antigen on Virus-Specific and Global T Cells in Patients With Chronic Hepatitis B Virus infection.

BACKGROUND & AIMS: Chronic hepatitis B virus (HBV) infection is characterized by the presence of defective viral envelope proteins (hepatitis B surface antigen [HBsAg]) and the duration of infection-most patients acquire the infection at birth or during the first years of life. We investigated the effects of these factors on patients' lymphocyte and HBV-specific T-cell populations. METHODS: We collected blood samples and clinical data from 243 patients with HBV infection (3-75 years old) in the United Kingdom and China. We measured levels of HBV DNA, HBsAg, hepatitis B e antigen, and alanine aminotransferase; analyzed HBV genotypes; and isolated peripheral blood mononuclear cells (PBMCs). In PBMCs from 48 patients with varying levels of serum HBsAg, we measured 40 markers on nature killer and T cells by mass cytometry. PBMCs from 189 patients with chronic infection and 38 patients with resolved infections were incubated with HBV peptide libraries, and HBV-specific T cells were identified by interferon gamma enzyme-linked immune absorbent spot (ELISpot) assays or flow cytometry. We used multivariate linear regression and performed variable selection using the Akaike information criterion to identify covariates associated with HBV-specific responses of T cells. RESULTS: Although T- and natural killer cell phenotypes and functions did not change with level of serum HBsAg, numbers of HBs-specific T cells correlated with serum levels of HBsAg (r = 0.3367; P < .00001). After we performed the variable selection, the multivariate linear regression model identified patient age as the only factor significantly associated with numbers of HBs-specific T cells (P = .000115). In patients younger than 30 years, HBs-specific T cells constituted 28.26% of the total HBV-specific T cells; this value decreased to 7.14% in patients older than 30 years. CONCLUSIONS: In an analysis of immune cells from patients with chronic HBV infection, we found that the duration of HBsAg exposure, rather than the quantity of HBsAg, was associated with the level of anti-HBV immune response. Although the presence of HBs-specific T cells might not be required for the clearance of HBV infection in all patients, strategies to restore anti-HBV immune responses should be considered in patients younger than 30 years.

Sodium bicarbonate supplements for treating acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a common, serious, but potentially treatable condition. Because AKI is often associated with acidosis, it has become common practice to recommend administration of sodium bicarbonate to correct acid imbalance. OBJECTIVES: To assess the benefits and harms of the use of sodium bicarbonate for people with AKI. The primary outcome measure was all-cause mortality, and secondary outcome measures were patients' need for renal replacement therapy; return to baseline kidney function; and overall survival. SEARCH METHODS: In November 2011 we searched the Cochrane Renal Group's Specialised Register using keywords relevant to this review. The register is populated using searches of Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE and handsearching records from renal-related journals and conference proceedings. SELECTION CRITERIA: All randomised controlled trials (RCTs) that investigated the use of sodium bicarbonate supplements, administered by any route, for the treatment of adults with AKI were to be included. The search strategy did not restrict inclusion based on an upper age limit or publication language. We did not consider inclusion of studies that investigated use of sodium bicarbonate for AKI prevention. DATA COLLECTION AND ANALYSIS: All authors planned to independently assess and extracted information. Information was to be collected on methods, participants, interventions and outcomes. Results were to be expressed as risk ratios (RR) for dichotomous outcomes or as mean differences (MD) for continuous data with 95% confidence intervals (CI). MAIN RESULTS: Although our literature search identified four studies, none of these met our predetermined selection criteria. Hence, no suitable studies were identified for inclusion in this review. AUTHORS' CONCLUSIONS: We found no RCT evidence - supportive or otherwise - for the use of sodium bicarbonate for people with AKI. We concluded that there is an urgent need for well conducted RCTs in this area.

Hepatitis B virus-specific T cells associate with viral control upon nucleos(t)ide-analogue therapy discontinuation.

BACKGROUND: The clinical management of chronic hepatitis B virus (HBV) patients is based exclusively on virological parameters that cannot independently determine in which patients nucleos(t)ide-analogue (NUC) therapy can be safely discontinued. NUCs efficiently suppress viral replication, but do not eliminate HBV. Thus, therapy discontinuation can be associated with virological and biochemical relapse and, consequently, therapy in the majority is life-long. METHODS: Since antiviral immunity is pivotal for HBV control, we investigated potential biomarkers for the safe discontinuation of NUCs within immune profiles of chronic HBV patients by utilizing traditional immunological assays (ELISPOT, flow cytometry) in conjunction with analyses of global non-antigen-specific immune populations (NanoString and CyTOF). Two distinct cohorts of 19 and 27 chronic HBV patients, respectively, were analyzed longitudinally prior to and after discontinuation of 2 different NUC therapy strategies. RESULTS: Absence of hepatic flares following discontinuation of NUC treatment correlated with the presence, during NUC viral suppression, of HBV core and polymerase-specific T cells that were contained within the ex vivo PD-1+ population. CONCLUSIONS: This study identifies the presence of functional HBV-specific T cells as a candidate immunological biomarker for safe therapy discontinuation in chronic HBV patients. Furthermore, the persistent and functional antiviral activity of PD-1+ HBV-specific T cells highlights the potential beneficial role of the expression of T cell exhaustion markers during human chronic viral infection. FUNDING: This work was funded by a Singapore Translational Research Investigator Award (NMRC/STaR/013/2012), the Eradication of HBV TCR Program (NMRC/TCR/014-NUHS/2015), the Singapore Immunology Network, the Wellcome Trust (107389/Z/15/Z), and a Barts and The London Charity (723/1795) grant.

The influence of 10 min of the Johrei healing method on laboratory stress.

OBJECTIVE: Johrei has been shown to decrease exam stress responses but its immediate effects have not been assessed. DESIGN: In a randomised, blinded, counter-balanced design, 33 medical students were asked to calculate mental arithmetic in the Paced Auditory Serial Addition Task (PASAT), which served as an acute stressor prior to two conditions, 10 min of Johrei or a control resting condition involving 10 min without Johrei in a cross-over trial; after each, saliva was collected and mood tested. SETTING: University EEG laboratory. INTERVENTION: Johrei, a non-touch healing method. MAIN OUTCOME MEASURES: Profile of mood states (POMS-Bi); state anxiety (STAI); salivary variables: cortisol, DHEA, IgA. RESULTS: Mood scores on 5/6 of the POMS-Bi subscales were slightly but significantly more positive in the Johrei condition. State anxiety was similarly decreased. IgA levels were unchanged but cortisol levels were found to be slightly but non-significantly lower after Johrei than after the control condition and DHEA levels slightly but non-significantly raised, with a negative correlation between cortisol and DHEA levels. CONCLUSIONS: This study gives some indication that Johrei can reduce negative mood and increase positive mood states after the acute effects of a laboratory stressor in comparison to a resting control condition.