Factors Associated with Hepatitis B Surface Antigen Kinetics and Responses in Pegylated Interferon Alpha-2a Monotherapy for Patients with Chronic Hepatitis B

Objective Pegylated-interferon monotherapy is the standard treatment for patients with chronic hepatitis B; however, the factors associated with its therapeutic effects remain unclear. Methods Patients with chronic hepatitis B were treated with pegylated interferon α-2a for 48 weeks. We evaluated the kinetics of hepatitis B surface antigen (HBsAg) during treatment and follow-up periods and the factors associated with an HBsAg response (defined as a change in HBsAg of ≥-1 log IU/mL from baseline). Results The study population comprised 50 patients. The median baseline levels of hepatitis B virus DNA and HBsAg were 5.00 and 3.40 log IU/mL. The median values of HBsAg reduction from baseline were -0.44 (n=48), -0.41 (n=40), and -0.68 (n=11) log IU/mL at the end of treatment and at 48 and 144 weeks post-treatment, respectively. The rates of HBsAg response were 24.0% and 22.5% at the end of treatment and at 48 weeks post-treatment, respectively. A multivariate analysis identified HBsAg <3.00 log IU/mL as an independent baseline factor contributing to the HBsAg response at the end of treatment and 48 weeks post-treatment (p=1.07×10^-2 and 4.42×10^-2, respectively). There were significant differences in the reduction of the HBsAg levels at 12 weeks of treatment and in the incidence of serum ALT increase during treatment between patients with and without an HBsAg response. Conclusion These findings suggest that the baseline HBsAg level, HBsAg kinetics at 12 weeks of treatment, and ALT increase during treatment are important factors contributing to the HBsAg response in pegylated interferon α-2a monotherapy for patients with chronic hepatitis B.     

Accurate quantification of urinary metabolites for predictive models manifest clinicopathology of renal cell carcinoma

Using surgically resected tissue, we identified characteristic metabolites related to the diagnosis and malignant status of clear cell renal cell carcinoma (ccRCC). Specifically, we quantified these metabolites in urine samples to evaluate their potential as clinically useful noninvasive biomarkers of ccRCC. Between January 2016 and August 2018, we collected urine samples from 87 patients who had pathologically diagnosed ccRCC and from 60 controls who were patients with benign urological conditions. Metabolite concentrations in urine samples were investigated using liquid chromatography‐mass spectrometry with an internal standard and adjustment based on urinary creatinine levels. We analyzed the association between metabolite concentration and predictability of diagnosis and of malignant status by multiple logistic regression and receiver operating characteristic (ROC) curves to establish ccRCC predictive models. Of the 47 metabolites identified in our previous study, we quantified 33 metabolites in the urine samples. Multiple logistic regression analysis revealed 5 metabolites (l ‐glutamic acid, lactate, d ‐sedoheptulose 7‐phosphate, 2‐hydroxyglutarate, and myoinositol) for a diagnostic predictive model and 4 metabolites (l ‐kynurenine, l ‐glutamine, fructose 6‐phosphate, and butyrylcarnitine) for a predictive model for clinical stage III/IV. The sensitivity and specificity of the diagnostic predictive model were 93.1% and 95.0%, respectively, yielding an area under the ROC curve (AUC) of 0.966. The sensitivity and specificity of the predictive model for clinical stage were 88.5% and 75.4%, respectively, with an AUC of 0.837. In conclusion, quantitative analysis of urinary metabolites yielded predictive models for diagnosis and malignant status of ccRCC. Urinary metabolites have the potential to be clinically useful noninvasive biomarkers of ccRCC to improve patient outcomes.     

Visceral Fat Accumulation is Associated with Mild Cognitive Impairment in Community-Dwelling Older Japanese Women

Visceral fat accumulation is detrimental for brain health and is associated with cognitive impairment in older adults. The objectives of the present study were to examine the association between visceral fat accumulation and prevalence of mild cognitive impairment and its subtypes. Design: a cross-sectional study. This study enrolled 6,109 community-dwelling older adults, including 3,434 women (mean age: 74.4 years) and 2,675 men (mean age: 74.3 years). Individuals with dementia, Parkinson’s disease, stroke, Mini-Mental State Examination scores ≤23, and who could not perform basic activities of daily living independently were excluded. Participants underwent neurocognitive assessments to assess mild cognitive impairment (MCI) and its subtypes. Visceral fat area (VFA) was measured using abdominal bioelectrical impedance analysis. Participants were divided into quartile groups by VFA. There were 731 (21.3%) women and 562 (21.0%) men with MCI, and the median VFA values were 63.3 cm2 and 96.3 cm2, respectively. Women participants in the second (adjusted odds ratios [aOR], 0.71; 95% confidence interval [95% CI], 0.54–0.94), third (aOR, 0.66; 95% CI, 0.47–0.92), and fourth quartiles of VFA (aOR, 0.62; 95% CI, 0.41–0.93) had a significantly lower risk of MCI than those in the first quartile. Higher VFA quartiles in women were associated with lower risk of non-amnestic MCI. There were no significant differences in men between quartiles. Visceral fat accumulation was associated with MCI, especially non-amnestic MCI, in community-dwelling older Japanese women. These results suggest that visceral fat accumulation is partially protective against cognitive impairment.