Cost-effectiveness of noninvasive liver fibrosis tests for treatment decisions in patients with chronic hepatitis C

The cost-effectiveness of noninvasive tests (NITs) as alternatives to liver biopsy is unknown. We compared the cost-effectiveness of using NITs to inform treatment decisions in adult patients with chronic hepatitis C (CHC). We conducted a systematic review and meta-analysis to calculate the diagnostic accuracy of various NITs using a bivariate random-effects model. We constructed a probabilistic decision analytical model to estimate health care costs and outcomes (quality-adjusted life-years; QALYs) using data from the meta-analysis, literature, and national UK data. We compared the cost-effectiveness of four treatment strategies: testing with NITs and treating patients with fibrosis stage ≥F2; testing with liver biopsy and treating patients with ≥F2; treat none; and treat all irrespective of fibrosis. We compared all NITs and tested the cost-effectiveness using current triple therapy with boceprevir or telaprevir, but also modeled new, more-potent antivirals. Treating all patients without any previous NIT was the most effective strategy and had an incremental cost-effectiveness ratio (ICER) of £9,204 per additional QALY gained. The exploratory analysis of currently licensed sofosbuvir treatment regimens found that treat all was cost-effective, compared to using an NIT to decide on treatment, with an ICER of £16,028 per QALY gained. The exploratory analysis to assess the possible effect on results of new treatments, found that if SVR rates increased to >90% for genotypes 1-4, the incremental treatment cost threshold for the "treat all" strategy to remain the most cost-effective strategy would be £37,500. Above this threshold, the most cost-effective option would be noninvasive testing with magnetic resonance elastography (ICER=£9,189). Conclusions: Treating all adult patients with CHC, irrespective of fibrosis stage, is the most cost-effective strategy with currently available drugs in developed countries. © 2014 The Authors

Cost-effectiveness of noninvasive liver fibrosis tests for treatment decisions in patients with chronic hepatitis B in the UK: systematic review and economic evaluation

The copyright line for this article was changed on 18 November 2016 after original online publication. Abbreviations: CEAF cost-effectiveness frontier. CHB chronic hepatitis B. CI confidence intervals. FN false negative. FP false positive. HBV hepatitis B virus. HCC hepatocellular carcinoma. ICER incremental cost-effectiveness ratio. NITs noninvasive tests. QUADAS Quality Assessment of Diagnostic Accuracy Studies. QUALYs quality-adjusted-life-years. TN true negative. TP true positive.Copyright © 2015 The Authors. We compared the cost-effectiveness of various noninvasive tests (NITs) in patients with chronic hepatitis B and elevated transaminases and/or viral load who would normally undergo liver biopsy to inform treatment decisions. We searched various databases until April 2012. We conducted a systematic review and meta-analysis to calculate the diagnostic accuracy of various NITs using a bivariate random-effects model. We constructed a probabilistic decision analytical model to estimate health care costs and outcomes quality-adjusted-life-years (QALYs) using data from the meta-analysis, literature, and national UK data. We compared the cost-effectiveness of four decision-making strategies: testing with NITs and treating patients with fibrosis stage ≥F2, testing with liver biopsy and treating patients with ≥F2, treat none (watchful waiting) and treat all irrespective of fibrosis. Treating all patients without prior fibrosis assessment had an incremental cost-effectiveness ratio (ICER) of £28 137 per additional QALY gained for HBeAg-negative patients. For HBeAg-positive patients, using Fibroscan was the most cost-effective option with an ICER of £23 345. The base case results remained robust in the majority of sensitivity analyses, but were sensitive to changes in the ≥F2 prevalence and the benefit of treatment in patients with F0–F1. For HBeAg-negative patients, strategies excluding NITs were the most cost-effective: treating all patients regardless of fibrosis level if the high cost-effectiveness threshold of £30 000 is accepted; watchful waiting if not. For HBeAg-positive patients, using Fibroscan to identify and treat those with ≥F2 was the most cost-effective option.The analysis for Hepatitis B was part of a larger project funded by The National Institute for Health Research Health Technology Assessment (HTA project 09/114/02) and will be published in full in the Health Technology Assessment journal series. Visit the HTA programme website for more details www.hta.ac.uk/link to project page

Electroluminescence from C- and Si- rich silicon oxides in continuous wave and pulsed excitation

International audienceThis work reports the electroluminescence from carbon-and silicon-rich silicon oxide layers under continuous wave and pulsed excitation. The films were fabricated by Si and C ion implantation at low energy in 40 nm thick SiO2, followed by annealing at 1100degC. In continuous wave excitation, white electroluminescence has been observed. Structural and optical studies allow assigning it to Si nanocrystals for the red part of the spectrum, and to C-related centers for the blue and green components. The external efficiency has been estimated to 10-4%. Electrical characteristics show a Fowler-Nordheim behavior for voltages above 25 V, equal to the onset of electroluminescence. This suggests that light emission is related to the impact ionization of radiative centers. In pulsed excitation, electroluminescence has been observed for a voltage of less than 10 V. It is shown that the C-rich centers are not involved in this process, but a solution to obtain their excitation is proposed

Cardiovascular morbidity and mortality is increased post-liver transplantation even in recipients with no pre-existing risk factors

Background/aims: Post-liver transplant (LT) metabolic syndrome (PTMS) and cardiovascular (CVS) mortality are becoming increasingly prevalent following sustained improvements in post-LT survival. We investigated the prevalence and predictors of PTMS and CVS complications in a cohort of consecutive LT recipients. Methods: We reviewed prospectively collected data of patients (n = 928) who underwent LT (1995-2013) and survived at least 1-year post-LT or died before that due to a major CVS complication. Results: Median follow-up was 85 months (IQR = 106). The prevalence of PTMS was 22.4% and it developed de novo in 183 recipients (19.7%). A total of 187 (20.2%) patients developed at least one CVS event post-LT within a median of 49 months (IQR = 85). Overall mortality rate was 22.6% (n = 210). Causes of death were CVS events (n = 45, 21.4%), malignancies (21%), liver-related deaths (20%) and infections (6.7%). Independent predictors of major CVS events were: documented CVS disease pre-LT (Hazard Ratio (HR) = 3.330; 95% CI = 1.620-6.840), DM (HR = 1.120; 95% CI 1.030-1.220), hypertension (HR = 1.140; 95% CI 1.030-1.270), dyslipidaemia (HR = 1.140; 95% CI 1.050-1.240) and creatinine levels at 1 year (HR = 1.010; 95% CI = 1.005-1.013). Among LT recipients without pre-LT CVS disease or MS components (n = 432), 85 recipients developed ≥1 CVS events (19.7%) with independent predictors being DM (HR = 1.150; 95% CI = 1.010-1.320), creatinine levels at 1 year (HR = 1.020; 95% CI = 1.010-1.030) and hypertension (HR = 1.190; 95% CI = 1.040-1.360). Conclusions: Post-LT patients are at increased risk of CVS morbidity even in the absence of pre-existing metabolic risk factors. Renal sparing immunosuppressive protocols might reduce CVS events post-LT

Hydrogen bond dynamics in the active site of photoactive yellow protein

Hydrogen bonds play major roles in biological structure and function. Nonetheless, hydrogen-bonded protons are not typically observed by X-ray crystallography, and most structural studies provide limited insight into the conformational plasticity of individual hydrogen bonds or the dynamical coupling present within hydrogen bond networks. We report the NMR detection of the hydrogen-bonded protons donated by Tyr-42 and Glu-46 to the chromophore oxygen in the active site of the bacterial photoreceptor, photoactive yellow protein (PYP). We have used the NMR resonances for these hydrogen bonds to probe their conformational properties and ability to rearrange in response to nearby electronic perturbation. The detection of geometric isotope effects transmitted between the Tyr-42 and Glu-46 hydrogen bonds provides strong evidence for robust coupling of their equilibrium conformations. Incorporation of a modified chromophore containing an electron-withdrawing cyano group to delocalize negative charge from the chromophore oxygen, analogous to the electronic rearrangement detected upon photon absorption, results in a lengthening of the Tyr-42 and Glu-46 hydrogen bonds and an attenuated hydrogen bond coupling. The results herein elucidate fundamental properties of hydrogen bonds within the complex environment of a protein interior. Furthermore, the robust conformational coupling and plasticity of hydrogen bonds observed in the PYP active site may facilitate the larger-scale dynamical coupling and signal transduction inherent to the biological function that PYP has evolved to carry out and may provide a model for other coupled dynamic systems