HBeAg Levels Vary across the Different Stages of HBV Infection According to the Extent of Immunological Pressure and Are Associated with Therapeutic Outcome in the Setting of Immunosuppression-Driven HBV Reactivation.

HBeAg is a marker of HBV-activity, and HBeAg-loss predicts a favorable clinical outcome. Here, we characterize HBeAg-levels across different phases of HBV infection, their correlation with virological/biochemical markers and the virological response to anti-HBV therapy. Quantitative HBeAg (qHBeAg, DiaSorin) is assessed in 101 HBeAg+ patients: 20 with acute-infection, 20 with chronic infection, 32 with chronic hepatitis and 29 with immunosuppression-driven HBV-reactivation (HBV-R). A total of 15/29 patients with HBV-R are monitored for >12 months after starting TDF/ETV. qHBeAg is higher in immunosuppression-driven HBV-R (median[IQR]:930[206-1945]PEIU/mL) and declines in chronic hepatitis (481[28-1393]PEIU/mL, p = 0.03), suggesting HBeAg production, modulated by the extent of immunological pressure. This is reinforced by the negative correlation between qHBeAg and ALT in acute infection (Rho = -0.66, p = 0.006) and chronic hepatitis (Rho = -0.35; p = 0.05). Interestingly, qHBeAg strongly and positively correlates with qHBsAg across the study groups, suggesting cccDNA as a major source of both proteins in the setting of HBeAg positivity (with limited contribution of integrated HBV-DNA to HBsAg production). Focusing on 15 patients with HBV-R starting TDF/ETV, virological suppression and HBeAg-loss are achieved in 60% and 53.3%. Notably, the combination of qHBeAg > 2000 PEIU/mL + qHBsAg > 52,000 IU/mL at HBV-R is the only factor predicting no HBeAg loss (HBeAg loss: 0% with vs. 72.7% without qHBeAg > 2000 PEIU/mL + qHBsAg > 52,000 IU/mL, p = 0.03). In conclusion, qHBeAg varies over the natural course of HBV infection, according to the extent of immunological pressure. In the setting of HBV-R, qHBeAg could be useful in predicting the treatment response under immunosuppression.

Rare benign tumors of the liver: still rare?

BACKGROUND: Benign liver tumors are common. They do not spread to other areas of the body, and they usually do not pose a serious health risk. In fact, in most cases, benign liver tumors are not diagnosed because patients are asymptomatic. When they are detected, it's usually because the person has had medical imaging tests, such as an ultrasound (US), computed tomography (CT) scan, or magnetic resonance imaging (MRI), for another condition. MATERIALS AND METHODS: A search of the literature was made using cancer literature and the PubMed, Scopus, and Web of Science (WOS) database for the following keywords: "hepatic benign tumors", "hepatic cystic tumors", "polycystic liver disease", "liver macroregenerative nodules", "hepatic mesenchymal hamartoma", "hepatic angiomyolipoma", "biliary cystadenoma", and "nodular regenerative hyperplasia". DISCUSSION AND CONCLUSION: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world; there is an increasing incidence worldwide. Approximately 750,000 new cases are reported per year. More than 75 % of cases occur in the Asia-Pacific region, largely in association with chronic hepatitis B virus (HBV) infection. The incidence of HCC is increasing in the USA and Europe because of the increased incidence of hepatitis C virus (HCV) infection. Unlike the liver HCC, benign tumors are less frequent. However, they represent a chapter always more interesting of liver disease. In fact, a careful differential diagnosis with the forms of malignant tumor is often required in such a way so as to direct the patient to the correct therapy. In conclusion, many of these tumors present with typical features in various imaging studies. On occasions, biopsies are required, and/or surgical removal is needed. In the majority of cases of benign hepatic tumors, no treatment is indicated. The main indication for treatment is the presence of significant clinical symptoms or suspicion of malignancy or fear of malignant transformation.

Monoclonal antibodies for the treatment of severe asthma.

Patients with severe asthma have a significant unmet need with persistent symptoms and/or frequent exacerbations despite treatment with high-dose steroid and other currently available therapies. These patients are also at risk of developing steroid-related side effects, and their severe, unrelenting symptoms have a huge impact on health care resources due to frequent hospital admissions and requirement for intensive medication use. Consequently, a compelling need exists for more effective and safer pharmacotherapies to help them achieve adequate disease control. Recent novel therapies for severe asthma are now emerging, some of the most promising of which are monoclonal antibodies. Monoclonal antibodies represent a form of immunotherapy used in a wide variety of therapeutic roles. The spectrum of disease states in which monoclonal antibodies have been approved for therapeutic use now includes respiratory and allergic diseases. At present, only one drug is licensed for allergic asthmatics with severe disease, omalizumab. We review some of the currently available biologics that are approved or under investigation for use in severe asthma. Some have shown to be useful in specifically targeted subpopulations of patients with severe asthma, whereas other have proven to be unsafe and/or unsuccessful. Despite these developments, more effort should be devoted to identifying new molecular targets, testing innovative approaches, and establishing the best use of what is available. Regarding this latter point, identifying individual characteristics that predict successful responses to these treatments is highly desirable.

Circulating endothelial-coagulative activation markers after smoking cessation: a 12-month observational study.

BACKGROUND: Cigarette smoking is associated with cardiovascular morbidity and mortality. Exposure to cigarette smoke can cause endothelial dysfunction with impaired endothelium-dependent vasodilation and 'endothelial activation', which predispose to atherothrombosis. The effects of continued smoking and smoking cessation on the level of endothelial, platelet and clotting activation have not been described previously. Here, we prospectively monitored changes in circulating endothelial-coagulative activation markers in smokers undertaking smoking cessation. METHOD: This 12-month prospective study of 174 smokers with no commonly acquired atherothrombotic risk factors underwent an intensive smoking-cessation programme investigating the effect of quitting on circulating levels of von Willebrand's Factor Antigen (vWF:Ag), soluble Thrombomodulin (sTM), d-Dimer (d-D), prothrombin fragment F1+2 (F1+2), platelet factor-4 (PF4) and ß-Thromboglobulin (ß-TG). Blood samples and study measures were collected and compared at baseline and at 2, 6 and 12months after smoking cessation from quitters and relapsers'. RESULTS: No significant differences in demographic or laboratory parameters at baseline were observed between the study groups. Significant changes in von Willebrand's Factor activity were observed at 2months after smoking cessation, with levels decreasing from 141·8% to 113·6%. Substantial modifications in d-Dimer, prothrombin fragment F1 +2, platelet factor-4 and ß-thromboglobulin concentrations were observed only at 6 and 12months after smoking cessation. Positive associations between baseline levels of these biomarkers and number of pack per years have been demonstrated. CONCLUSIONS: Chronic exposure to cigarette smoke sustains the activation of the endothelial-coagulative system and abstinence may result in the improvement of several endothelial-coagulative abnormalities in regular smokers. This may translate into an overall decline in cardiovascular risk.