Long-term Clinical Outcome of Treatment for Chronic Hepatitis C

Worldwide, 170 million people are chronically infected with the hepatitis C virus. The infection leads to inflammation and fibrosis of the liver and may eventually lead to liver failure or development of hepatocellular carcinoma. It is known that treatment with pegylated interferon and ribavirin may lead to sustained suppression of the hepatitis C virus. The aim of this thesis is to investigate whether patients with a sustained virological response have a prolonged life expectancy and whether they have a decreased risk of developing liver failure and hepatocellular carcinoma. In a first study we compared the survival of chronic hepatitis C patients from different European centers with the general population. Patients with a sustained virological response had a life expectancy similar to the general population, matched for age and gender. We also investigated patients with advanced liver fibrosis. In this study, data were collected from more than 500 European and Canadian patients. Among sustained virological responders there was a spectaculair decrease in the risk of developing liver failure and the 5-year risk of dying from a liver-related cause had decreased from 12.9 to 4.4 percent, compared to non-responders. Finally, the course of the disease in treated patients with advanced fibrosis was compared to the natural history, as predicted by a mathematical model. This comparison also suggested an improved outcome for patients who had undergone treatment with peginterferon and ribavirin. For this work, B.J. Veldt received a stipend from the Netherlands organisation for health research and development

A Successful Broker Agent for Power TAC

The Power TAC simulates a smart grid energy market. In this simulation, broker agents compete for customers on a tariff market and trade energy on a wholesale market. It provides a platform for testing strategies of broker agents against other strategies. In this paper we describe the strategies of our broker agent. Amongst others, due to a beneficial trading technique related to equilibria in continuous auctions on the wholesale market and a strategy inspired by Tit-for-Tat in the Iterated Prisoner's Dilemma game on the tariff market, our broker ended second in the 2013 Power TAC

The treatment of hepatitis C: history, presence and future

The treatment of chronic hepatitis C has made remarkable progress over the past two decades. For interferon-alpha monotherapy, sustained virological response rates were between 2 and 9% in genotype 1 and between 16 and 23% in genotypes 2 and 3. By adjusting treatment duration up to 48 weeks for genotype 1 and combining regular interferon-alpha with ribavirin, sustained response rates could be improved to 28 to 31% in genotype 1 and around 65% in genotypes 2 and 3. Attempts to further increase efficacy included the addition of amantadine without conclusive evidence up till now. With the recent introduction of long-acting pegylated interferon-alpha in combination with ribavirin, sustained virological response rates of 8o% can be obtained in genotypes 2 and 3. However, sustained virological response rates for patients with either genotype 1, nonresponse to prior treatment, cirrhosis or a combination of these characteristics are still less than 50%. In view of results with daily high-dose interferon-alpha induction in combination with prolongation of treatment duration up to 18 months, such patients might benefit from induction and prolonged PEG-IFN-alpha treatment and should be treated in an experimental setting

Sickle cell patients are characterized by a reduced glycocalyx volume

The glycocalyx is an important anti-inflammatory and anti-adhesive barrier at the luminal side of endothelial cells. Glycocalyx volume was significantly reduced in sickle cell patients (HbSS/HbSβ0-thalassemia median 0.47L, IQR 0.27-0.66, HbSC/HbSβ+-thalassemia 0.23L, 0.0-0.58) compared with controls (1×109L, 0.52-1.77) (p=0.03). Reduced glycocalyx may be a new factor in the pathophysiology of sickle cell disease

Електрофізичні властивості системи політетрафторетилен – вуглецеві нанотрубки

Проведено дослідження комплексної діелектричної проникності та електропровідності в надвисокочастотному діапазоні (9 ГГц) і на низьких частотах (0,1; 1 та 10 кГц) двох систем політетрафторетилен – багатошарові вуглецеві нанотрубки з вихідними та диспергованими у водному середовищі . Введення диспергованих нанотрубок в полімер знижує поріг перколяції з 4,5 % до 2,6 % (мас.) за рахунок рівномірного розподілу наповнювача у полімері, що призводить до зростання міжфазної поверхні взаємодії полімер – вуглецеві нанотрубки, яка проявляється в збільшенні значень дійсної та уявної складової комплексної діелектричної проникності.Проведены исследования комплексной диэлектрической проницаемости и электропроводности в сверхвысокочастотном диапазоне (9 ГГц) и на низких частотах (0,1; 1; 10 кГц) двух систем политетрафторэтилен–многослойные углеродные нанотрубки с исходными и диспергированными у водной среде. Введение диспергированных нанотрубок в полимер снижает порог перколяции с 4,5% до 2,6 % (масс.) за счет равномерного распределения наполнителя в полимере, что приводит к возрастанию межфазной поверхности взаимодействия полимер – углеродные нанотрубки, которая проявляется в увеличении значений действительной и мнимой составляющей комплексной диэлектрической проницаемости.Complex dielectric permeability and conductivity of two systems, namely polytetrafluorethylene – intact carbon nanotubes and polytetrafluorethylene – carbon nanotubes dispersed in aqueous media, has been studied in super high-frequency range (9 GHz) and at low frequencies (0,1; 1 and 10 kHz). Doping of the polymer with the dispersed nanotubes decreases percolation threshold (limit ) from 4,5 wt. % to 2,6 wt. % due to uniform distribution of the filler in the polymer. This results to increase of interface interaction polymer - carbon nanotubes that is demonstrated by increase of value of real and imaginary component of complex dielectric permeability

Management of Thrombocytopenia in Chronic Liver Disease: Focus on Pharmacotherapeutic Strategies

Thrombocytopenia (platelet count <150 × 109/L) often complicates chronic liver disease, impeding optimal management of these patients. The prevalence of this manifestation ranges from 6 % among non-cirrhotic patients with chronic liver disease to 70 % among patients with liver cirrhosis. It has also been shown that the severity of liver disease is associated with both prevalence and level of thrombocytopenia. Its development is often multifactorial, although thrombopoietin is thought to be a major factor. The discovery of and ability to clone thrombopoietin led to new treatment opportunities for this clinical manifestation. This review discusses data on the three most important thrombopoietin receptor agonists: eltrombopag, avatrombopag, and romiplostim. Currently, only eltrombopag is approved for usage among patients with thrombocytopenia and chronic hepatitis C virus infection in order to initiate and maintain interferon-based antiviral treatment. Nevertheless, the optimal management of hematologic abnormalities among patients with chronic liver disease, and its risk for bleeding complications, is still a matter of discussion. Thrombocytopenia definitely contributes to hemostatic defects but is often counterbalanced by the enhanced presence of procoagulant factors. Therefore, a thorough assessment of the patient's risk for thrombotic events is essential when the use of thrombopoietin receptor agonists is considered among patients with chronic liver disease and thrombocytopenia

Recipient IL28B polymorphism is an important independent predictor of posttransplant diabetes mellitus in liver transplant patients with chronic hepatitis C

IL28B polymorphisms are strongly associated with response to treatment for HCV infection. IL28B acts on interferon-stimulated genes via the JAK-STAT pathway, which has been implicated in development of insulin resistance. We investigated whether IL28B polymorphisms are associated with posttransplant diabetes mellitus (DM). Consecutive HCV patients who underwent liver transplantation between 1-1995 and 1-2011 were studied. Genotyping of the polymorphism rs12979860 was performed on DNA collected from donors and recipients. Posttransplant DM was screened for by fasting blood glucoses every 1-3 months. Of 221 included patients, 69 developed posttransplant DM (31%). Twenty-two patients with recipient IL28B genotype TT (48%), 25 with IL28B genotype CT (25%) and 22 with IL28B genotype CC (29%) developed posttransplant DM. TT genotype was statistically significantly associated with posttransplant DM over time (log rank p = 0.012 for TT vs. CT and p = 0.045 for TT vs. CC). Multivariate Cox regression analysis correcting for donor age, body mass index, baseline serum glucose, baseline serum cholesterol, recipient age and treated rejection, showed that recipient IL28B genotype TT was independently associated with posttransplant DM (hazard ratio 2.51; 95% confidence interval 1.17-5.40; p = 0.011). We conclude that the risk of developing posttransplant DM is significantly increased in recipients carrying the TT polymorphism of the IL28B gene. An analysis of liver transplant recipients with hepatitis C virus infection finds that the risk of developing posttransplant diabetes mellitus is significantly increased in recipients carrying the TT polymorphism of the IL28B gene

A human monoclonal antibody blocking SARS-CoV-2 infection

The emergence of the novel human coronavirus SARS-CoV-2 in Wuhan, China has caused a worldwide epidemic of respiratory disease (COVID-19). Vaccines and targeted therapeutics for treatment of this disease are currently lacking. Here we report a human monoclonal antibody that neutralizes SARS-CoV-2 (and SARS-CoV) in cell culture. This cross-neutralizing antibody targets a communal epitope on these viruses and may offer potential for prevention and treatment of COVID-19