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

A continuous-time hidden Markov model for cancer surveillance using serum biomarkers with application to hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer deaths worldwide, and its early detection is a critical determinant of whether curative treatment is achievable. Early stage HCC is typically asymptomatic. Thus, screening programmes are used for cancer detection in patients at risk of tumour development. Radiological screening methods are limited by imperfect data, cost and associated risks, and additionally are unable to detect lesions until they have grown to a certain size. Therefore, some screening programmes use additional blood/serum biomarkers to help identify individuals in whom to target diagnostic cancer investigations. The GALAD score, combining the levels of several blood biomarkers, age and sex, has been developed to identify patients with early HCC. Here we propose a Bayesian hierarchical model for an individual’s longitudinal GALAD scores whilst in HCC surveillance to identify potentially significant changes in the trend of the GALAD score, indicating the development of HCC, aiming to improve early detection compared to standard methods. An absorbent two-state continuous-time hidden Markov model is developed for the individual level longitudinal data where the states correspond to the presence/absence of HCC. The model is additionally informed by the information on the diagnosis by standard clinical practice, taking into account that HCC can be present before the actual diagnosis so that there may be false negatives within the diagnosis data. We fit the model to a Japanese cohort of patients undergoing HCC surveillance and show that the detection capability of this proposal is greater than using a fixed cut-point

Piezoelectric properties of high Curie temperature barium titanate-bismuth perovskite-type oxide system ceramics

Barium titanate (BaTiO3, BT)-bismuth magnesium titanium oxide [Bi(Mg0.5Ti0.5)O-3, BMT] system ceramics were prepared in an ambient atmosphere in order to increase the Curie temperature (T-c) of BT above 132 degrees C. A single perovskite phase was observed for BT-BMT ceramics with BMT compositions less than 50 mol %, and their relative densities were greater than 94%. Synchrotron measured x-ray diffraction patterns revealed that all the cations in the ceramics were homogeneously distributed. The temperature dependence of the dielectric properties revealed that the BT-BMT system ceramics exhibited relaxorlike characteristics with a dielectric maximum temperature as high as 360 degrees C for the 0.5BT-0.5BMT ceramic. The apparent piezoelectric constant (d*) was 60 pC/N for the 0.4BT-0.6BMT ceramic. Based upon these results, the BT-BMT system shows potential as a new type of lead-free material for high T-c piezoelectric applications