Impact of HBV Infection on Outcomes of Direct-Acting Antiviral Therapy of Chronic Hepatitis C

Background: Most clinical trials of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection have excluded hepatitis B virus (HBV) coinfection, and little is known about the effects of DAA on chronic hepatitis C patients with HBV coinfection. Recent studies have reported that DAA therapy for HCV can also cause HBV reactivation in patients with HBV and HCV coinfection. The aim of this study was to assess the effects of DAA on sustained virologic response (SVR) and HBV reactivation in patients with chronic hepatitis C. Methods: Participants comprised 199 chronic hepatitis C patients who received DAA therapy (96 men, 103 women; mean age, 66.7 ± 12.0 years). Results: Twelve patients were coinfected with HCV and HBV. Sixty patients were HBV surface antigen negative but positive for hepatitis B core antibody and/or hepatitis B surface antibody, and one hundred and twenty-seven patients had not been exposed to HBV. Rates of SVR in HBV and HCV coinfected patients, HBV prior infection, and no exposure to HBV were 100, 95, and 97%, respectively. Significant differences were seen between each group. No case showed HBV reactivation. Conclusions: DAA treatments were effective in patients with HBV coinfection or HBV prior infection, as well as HCV monoinfection. As the number of cases was small, we still suggest caution regarding HBV reactivation in HCV and HBV coinfected patients undergoing treatment with DAA

Proteomics analysis identified peroxiredoxin 2 involved in early-phase left ventricular impairment in hamsters with cardiomyopathy

<div><p>Given the hypothesis that inflammation plays a critical role in the progression of cardiovascular diseases, the aim of the present study was to identify new diagnostic and prognostic biomarkers of myocardial proteins involved in early-phase cardiac impairment, using proteomics analysis. Using the two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) combined with MALDI-TOF/TOF tandem mass spectrometry, we compared differences in the expression of proteins in the whole left ventricles between control hamsters, dilated cardiomyopathic hamsters (TO-2), and hypertrophy cardiomyopathic hamsters (Bio14.6) at 6 weeks of age (n = 6, each group). Proteomic analysis identified 10 protein spots with significant alterations, with 7 up-regulated and 3 down-regulated proteins in the left ventricles of both TO-2 and Bio 14.6 hamsters, compared with control hamsters. Of the total alterations, peroxiredoxin 2 (PRDX2) showed significant upregulation in the left ventricles of TO-2 and Bio 14.6 hamsters. Our data suggest that PRDX2, a redox regulating molecule, is involved in early-phase left ventricular impairment in hamsters with cardiomyopathy.</p></div

Amounts of PRDX in 6-week-old F1B, TO-2, and Bio 14.6 hamsters.

<p>(A) Representative immunoblots of each protein. (B) The amount of each protein quantitated relative to the amount of β-actin and expressed relative to the value of F1B control hamsters. Data are mean±SEM of six animals per group. *<i>P</i><0.05, versus F1B control hamsters. (C) Light micrographs of myocytes in hematoxylin-eosin stained sections and (D) immunohistochemical staining for PRDX in the left ventricles of representative F1B, TO-2, and Bio 14.6 hamsters. Scale bars, 100 μm.</p

List of proteins with significant differences in their levels in heart tissues of TO-2, Bio 14.6, and F1B hamsters.

<p>List of proteins with significant differences in their levels in heart tissues of TO-2, Bio 14.6, and F1B hamsters.</p

Gene expression of ANP, BNP, collagen I, and collagen III in 6-week-old F1B, TO-2, and Bio 14.6 hamsters.

<p>The mRNA levels of (A) ANP, (B) BNP, (C) collagen I, and (D) collagen III in the heart tissues were determined by quantitative RT-PCR analysis. Data are normalized by the abundance of GAPD mRNA. Quantitative data are expressed relative to the values for F1B hamsters. Data are mean s±SEM of six animals per group. *<i>P</i><0.05 versus F1B control hamsters.</p

Gene Ontology (GO) annotation of identified proteins.

<p>The graphs show the percentages of corresponding GO terms to the total number of annotated proteins. The identified up-regulated and down-regulated proteins were mapped to GO at (A) biological process and (B) molecular function.</p

Representative 2D-DIGE image and images of spots with significant alterations in LV lysates.

<p>(A) Proteins (40 μg each) were labeled with Cy3 and Cy5 dyes, mixed and subjected to 2D-DIGE analysis. Cy3- and Cy5- images are illustrated using red and green pseudocolors, respectively. Images were analyzed using DeCyder software. IPG strips (pI 3–11) were used for IEF, and 12.5% SDS-PAGE for the second dimension. (B) The 2-DE images of 4 spots showed significant alterations in the left ventricles of both TO-2 and Bio 14.6 hamsters, compared with F1B control hamsters.</p

Physiological data of 6-week-old F1B, TO-2, and Bio 14.6 hamsters.

<p>(A) Body weight, (B) LV weight/body weight, (C) thickness of the intra-ventricular septum, (D) LV end-diastolic dimension, (E) LV end-systolic dimension, and (F) fraction shortening. Data are mean±SEM of six animals per group. *<i>P</i><0.05 versus F1B control hamsters.</p