Hepatitis B virus infection Trépo, Christian, Prof; Chan, Henry L Y, Prof; Lok, Anna, Prof
The Lancet (British edition),
12/2014, Letnik:
384, Številka:
9959
Journal Article
Recenzirano
Summary Hepatitis B virus infection is a major public health problem worldwide; roughly 30% of the world's population show serological evidence of current or past infection. Hepatitis B virus is a ...partly double-stranded DNA virus with several serological markers: HBsAg and anti-HBs, HBeAg and anti-HBe, and anti-HBc IgM and IgG. It is transmitted through contact with infected blood and semen. A safe and effective vaccine has been available since 1981, and, although variable, the implementation of universal vaccination in infants has resulted in a sharp decline in prevalence. Hepatitis B virus is not cytopathic; both liver damage and viral control—and therefore clinical outcome—depend on the complex interplay between virus replication and host immune response. Overall, as much as 40% of men and 15% of women with perinatally acquired hepatitis B virus infection will die of liver cirrhosis or hepatocellular carcinoma. In addition to decreasing hepatic inflammation, long-term antiviral treatment can reverse cirrhosis and reduce hepatocellular carcinoma. Development of new therapies that can improve HBsAg clearance and virological cure is warranted.
On‐treatment levels of hepatitis B surface antigen (HBsAg) may predict response to peginterferon (PEG‐IFN) therapy in chronic hepatitis B (CHB), but previously proposed prediction rules have shown ...limited external validity. We analyzed 803 HBeAg‐positive patients treated with PEG‐IFN in three global studies with available HBsAg measurements. A stopping‐rule based on absence of a decline from baseline was compared to a prediction‐rule that uses HBsAg levels of <1,500 IU/mL and >20,000 IU/mL to identify patients with high and low probabilities of response. Patients with an HBsAg level <1,500 IU/mL at week 12 achieved response (HBeAg loss with HBV DNA <2,000 IU/mL at 6 months posttreatment) in 45%. At week 12, patients without a decline in HBsAg achieved a response in 14%, compared to only 6% of patients with HBsAg >20,000 IU/mL, but performance varied across HBV genotype. In patients treated with PEG‐IFN monotherapy (n = 465), response rates were low in patients with genotypes A or D if there was no decline of HBsAg by week 12 (negative predictive value NPV: 97%‐100%), and in patients with genotypes B or C if HBsAg at week 12 was >20,000 IU/mL (NPV: 92%‐98%). At week 24, nearly all patients with HBsAg >20,000 IU/mL failed to achieve a response, irrespective of HBV genotype (NPV for response and HBsAg loss 99% and 100%). Conclusion: HBsAg is a strong predictor of response to PEG‐IFN in HBeAg‐positive CHB. HBV genotype‐specific stopping‐rules may be considered at week 12, but treatment discontinuation is indicated in all patients with HBsAg >20,000 IU/mL at week 24, irrespective of HBV genotype. (Hepatology 2013;53:872–880)
Surface spin waves in thin permalloy films are studied by means of propagative-spin-wave spectroscopy. We observe a systematic difference of up to several tens of MHz when comparing the frequencies ...of counterpropagating waves. This frequency nonreciprocity effect is modeled using an analytical dipole-exchange theory that considers the mutual influence of nonreciprocal spin wave modal profiles and differences in magnetic anisotropies at the two film surfaces. At moderate film thickness (20 nm and below), the frequency nonreciprocity scales linearly with the wave vector and quadratically with the thickness, whereas a more complex nonmonotonic behavior is observed at larger thickness. Our paper suggests that surface wave frequency nonreciprocity can be used as an accurate spectroscopic probe of magnetic asymmetries in thin ferromagnetic films.
This Review presents current epidemiological trends of the most common liver diseases in Asia-Pacific countries. Hepatitis B virus (HBV) remains the primary cause of cirrhosis; despite declining ...prevalence in most Asian nations, this virus still poses a severe threat in some territories and regions. Mortality resulting from HBV infection is declining as a result of preventive measures and antiviral treatments. The epidemiological transition of hepatitis C virus (HCV) infection has varied in the region in the past few decades, but the medical burden of infection and the prevalence of its related cancers are increasing. The lack of licensed HCV vaccines highlights the need for novel treatment strategies. The prevalence of nonalcoholic fatty liver disease (NAFLD) has risen in the past decade, mostly owing to increasingly urbanized lifestyles and dietary changes. Alternative herbal medicine and dietary supplements are major causes of drug-induced liver injury (DILI) in some countries. Complications arising from these chronic liver diseases, including cirrhosis and liver cancer, are therefore emerging threats in the Asia-Pacific region. Key strategies to control these liver diseases include monitoring of at-risk populations, implementation of national guidelines and increasing public and physician awareness, in concert with improving access to health care.
With the rapidly growing popularity and sophistication of inhalation therapy, there is an increasing demand for tailor-made inhalable drug particles capable of affording the most efficient delivery ...to the lungs and the most optimal therapeutic outcomes. To cope with this formulation demand, a wide variety of novel particle technologies have emerged over the past decade. The present review is intended to provide a critical account of the current goals and technologies of particle engineering for the development of pulmonary drug delivery systems. These technologies cover traditional micronization and powder blending, controlled solvent crystallization, spray drying, spray freeze drying, particle formation from liquid dispersion systems, supercritical fluid processing and particle coating. The merits and limitations of these technologies are discussed with reference to their applications to specific drug and/or excipient materials. The regulatory requirements applicable to particulate inhalation products are also reviewed briefly.
The in vitro release study is a critical test to assess the safety, efficacy, and quality of nanoparticle-based drug delivery systems, but there is no compendial or regulatory standard. The variety ...of testing methods makes direct comparison among different systems difficult. We herein proposed a novel sample and separate (SS) method by combining the United States Pharmacopeia (USP) apparatus II (paddle) with well-validated centrifugal ultrafiltration (CU) technique that efficiently separated the free drug from nanoparticles. Polymeric drug nanoparticles were prepared by using a four-stream multi-inlet vortex mixer with d-α-tocopheryl polyethylene glycol 1000 succinate as a stabilizer. Itraconazole, cholecalciferol, and flurbiprofen were selected to produce three different nanoparticles with particle size <100 nm. By comparing with the dialysis membrane (DM) method and the SS methods using syringe filters, this novel SS + CU technique was considered the most appropriate in terms of the accuracy and repeatability to provide the in vitro release kinetics of nanoparticles. Interestingly, the DM method appeared to misestimate the release kinetics of nanoparticles through separate mechanisms. This work offers a superior analytical technique for studying in vitro drug release from polymeric nanoparticles, which could benefit the future development of in vitro-in vivo correlation of polymeric nanoparticles.
Efforts to estimate the physical and economic impacts of future climate change face substantial challenges. To enrich the currently popular approaches to impact analysis-which involve evaluation of a ...damage function or multi-model comparisons based on a limited number of standardized scenarios-we propose integrating a geospatially resolved physical representation of impacts into a coupled human-Earth system modeling framework. Large internationally coordinated exercises cannot easily respond to new policy targets and the implementation of standard scenarios across models, institutions and research communities can yield inconsistent estimates. Here, we argue for a shift toward the use of a self-consistent integrated modeling framework to assess climate impacts, and discuss ways the integrated assessment modeling community can move in this direction. We then demonstrate the capabilities of such a modeling framework by conducting a multi-sectoral assessment of climate impacts under a range of consistent and integrated economic and climate scenarios that are responsive to new policies and business expectations.
Significance We used massively parallel sequencing to study the size profiles of plasma DNA samples at single-base resolution and in a genome-wide manner. We used chromosome arm-level z -score ...analysis (CAZA) to identify tumor-derived plasma DNA for studying their specific size profiles. We showed that populations of aberrantly short and long DNA molecules existed in the plasma of patients with hepatocellular carcinoma. The short ones preferentially carried the tumor-associated copy number aberrations. We further showed that there were elevated amounts of mitochondrial DNA in the plasma of hepatocellular carcinoma patients. Such molecules were much shorter than the nuclear DNA in plasma. These findings have shed light on fundamental biological characteristics of plasma DNA and related diagnostic applications for cancer.
The analysis of tumor-derived circulating cell-free DNA opens up new possibilities for performing liquid biopsies for the assessment of solid tumors. Although its clinical potential has been increasingly recognized, many aspects of the biological characteristics of tumor-derived cell-free DNA remain unclear. With respect to the size profile of such plasma DNA molecules, a number of studies reported the finding of increased integrity of tumor-derived plasma DNA, whereas others found evidence to suggest that plasma DNA molecules released by tumors might be shorter. Here, we performed a detailed analysis of the size profiles of plasma DNA in 90 patients with hepatocellular carcinoma, 67 with chronic hepatitis B, 36 with hepatitis B-associated cirrhosis, and 32 healthy controls. We used massively parallel sequencing to achieve plasma DNA size measurement at single-base resolution and in a genome-wide manner. Tumor-derived plasma DNA molecules were further identified with the use of chromosome arm-level z -score analysis (CAZA), which facilitated the studying of their specific size profiles. We showed that populations of aberrantly short and long DNA molecules existed in the plasma of patients with hepatocellular carcinoma. The short ones preferentially carried the tumor-associated copy number aberrations. We further showed that there were elevated amounts of plasma mitochondrial DNA in the plasma of hepatocellular carcinoma patients. Such molecules were much shorter than the nuclear DNA in plasma. These results have improved our understanding of the size profile of tumor-derived circulating cell-free DNA and might further enhance our ability to use plasma DNA as a molecular diagnostic tool.
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