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Introduction: Measurement of hepatic venous pressure gradient (HVPG) is the gold standard for the assessment of portal hypertension (PH) and the prediction of clinical decompensation in patients with cirrhosis and PH. The development of non-invasive methodologies able to identify clinically significant PH and predict disease progression is needed. Indocyanine green clearance at 15 minutes (IcgR15) is an index of liver blood flow, functioning hepatocyte mass and energy status of the liver. In this ongoing study, we evaluate the ability of IcgR15 and other non-invasive tests to predict PH in patients with chronic liver disease of various etiology. Methods: Sixty-seven consecutive patients (43M/34F, mean age 61.09±12.57; age range 33 - 84 years) with chronic liver disease underwent HVPG measurement in our radiological unit between January and November 2010. All patients underwent laboratory tests, EGDS, abdominal ultrasound and IcgR15. Mann-Whitney test and multiple regression analysis has been performed in order to identify variables independently associated with HVPG>10mmHg, HVPG>12 and gastro-esophageal varices (GEV). ROC curves were used to define the best cut-off (Medcalc software v11.4). Results: Platelets count (P10 and HVPG>12 while bilirubin, albumin, INR, MELD, spleen diameter, APRI were not. On multiple regression both platelets count and IcgR15 were significantly related to HVPG>10 (respectively P=0.0004 and 0.02, r= -0.54 and r= 0.45) and HVPG>12 (respectively P=0.007 and P9.7% (sensitivity 83.0%, specificity 65.0%, AUROC 0.81, P10mmHg and PLT≤123.000 (sensitivity 76.3%, specificity 75.9%, AUROC 0.81, P12.4% (sensitivity 84.2%, specificity 72.4%, AUROC 0.87, P12mmHg. ROC curve identified IcgR15>10.5% as the best predictor of GEV presence (sensitivity 87.2%, specificity 67.9%, AUROC 0.80, P

Background and aim: Refractory ascites is an accepted indication for transjugular intrahepatic porto-systemic shunt. However, the factors associated with mortality after TIPS positioning for this specific indication are not well established yet. This retrospective analysis was conducted to investigate this issue. Material and methods: Patients who underwent TIPS for refractory ascites in the period 02/2003-01/2008 at our tertiary care Center were identified and were the subjects of our study. Kaplan-Meier curves were used to analyse long term survival. Cox proportional-hazards regression model was performed to assess risk factors for mortality, and factors significant at univariate analysis were entered in a multivariate model to identify independent predictors of mortality. ROC curves were used to define the best cut-off of continuous variables for mortality prediction. Patients who underwent orthotopic liver transplantation were censored at the moment of OLT. P values < 0.05 were considered statistically significant. Results: The study included 73 patients (67% males). Mean age at the time of TIPS creation was 57.4 years (range, 34-76 y). MELD score at the moment of TIPS positioning was 15.7±5.3. Mean survival after TIPS was 17±14 months. 12 patients (16.4%) underwent OLT, and 17 (23.3%) died during follow-up. At univariate analysis, increasing values of MELD score, TIPS Risk Score, AST, bilirubin, INR and HVPG at the time of TIPS placement significantly increased the risk of death on follow-up. In our population age, gender, creatinine and sodium were not associated to mortality. Multivariate analysis showed that MELD score, AST and HVPG were independent predictors of mortality overall. As expected, patients with MELD score

Alzheimer’s disease (AD) as well as osteoporosis are multifactorial progressive degenerative disorders characterized by low parenchymal density and microarchitectural deterioration of tissue. Though not referred to as one of the major complications of AD, osteoporosis and hip fracture are commonly observed in patients with AD, however, the mechanisms underlying this association remain poorly understood. Reactive oxygen species (ROS) are generally recognized as intracellular redox signaling molecules involved in the regulation of bone metabolism, including receptor activator of nuclear factor-kB ligand (RANKL)-dependent osteoclast differentiation, but they also have cytotoxic effects that include peroxidation of lipids and oxidative damage to proteins and DNA. ROS formation, which is positively implicated in cellular stress response mechanisms, is a highly regulated process controlled by a complex network of intracellular signaling pathways which regulate life span across species including vitagenes which are genes involved in preserving cellular homeostasis during stressful conditions. Vitagenes encode for heat shock proteins (Hsp) Hsp32, Hsp70, the thioredoxin and the sirtuin protein systems. Dietary antioxidants, have recently been demonstrated to be neuroprotective through the activation of hormetic pathways, including vitagenes. The hormetic dose–response, has the potential to affect significantly the design of pre-clinical studies and clinical trials as well as strategies for optimal patient dosing in the treatment of numerous diseases. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing stress responses. Here we focus on possible signaling mechanisms involved in bone remodeling and activation of vitagenes resulting in enhanced defense against energy and stress resistance homeostasis dysruption with consequent impact on aging processes.

Background Treatment of hepatitis C virus (HCV) recurrence after liver transplantation (LT) is difficult with low response rates. Aim To assess the safety and efficacy of pegylated-interferon (PEG-IFN) alfa-2b + ribavirin (RBV) in patients with post-LT recurrent genotype-1 HCV and to establish stopping rules according to response. Methods Fifty-three patients with post-LT HCV recurrence were enrolled. Patients received PEG-IFN alfa-2b 1.0 μ/kg/week plus RBV 8–10 mg/kg/day for 24 weeks. Those with ‘early virological response at week 24’ (EVR24) continued treatment for 24 weeks (group A). Patients without EVR24 were randomized to continue (group B) or to discontinue (group C). Results Overall sustained virological response (SVR) was 26% (14/53). Alanine aminotransferase, rapid virological response, EVR12, EVR24, undetectable serum HCV-RNA at weeks 12 (cEVR12) and 24 (cEVR24) were related to SVR. cEVR12 and cEVR24 (OR: 14.7; 95% CI: 2.02–106.4) were independent predictors of SVR. All patients with SVR, had cEVR12. No patient in groups B and C achieved end-of-treatment response. One patient in group B had SVR. Conclusions Pegylated-interferon alfa-2b was effective in one of four of patients with HCV genotype 1 after LT. Treatment should be discontinued in patients with no virological response at week 12. Further studies are needed to evaluate whether a longer treatment period may be beneficial in patients with ≥2 log10 drop in HCV-RNA at week 24