Vitamin D binding protein gene polymorphisms and baseline vitamin D levels as predictors of antiviral response in chronic hepatitis C

Vitamin D deficiency seems to predict the unsuccessful achievement of sustained viral response (SVR) after anti-viral treatment in hepatitis C virus (HCV) difficult to treat genotypes. Vitamin D binding protein (GC) gene polymorphisms are known to influence vitamin D levels. This study was performed to assess whether the interaction between basal circulating vitamin D and the GC polymorphism plays a role in influencing the rate of anti viral responses in patients affected by chronic hepatitis C. Two hundred six HCV patients treated with a combination therapy of PEGinterferon plus ribavirin were retrospectively evaluated. GC rs7041 G>T, GC rs4588 C>A and IL- 28B rs12979860 C>T polymorphisms were genotyped. Frequencies of GC rs7041 G>T and rs4588 C>A polymorphisms were: G/G=64 (31.1%), G/T=100 (48.5%), T/T=42 (20.4%) and C/C=108 (52.4%), C/A=84 (40.8%), A/A=14 (6.8%). Patients were divided into those carrying 653 major alleles (WT+: G-C/G-C, G-C/T-C, G-C/G-A, N=100) and the remaining (WT-: G-C/T-A, T-A/T-C, T-A/T-A, T-C/T-C, N=106). Four groups were identified: vitamin D 6420 ng/mL and WT-, vitamin D 6420 and WT+, vitamin D>20 and WT-, vitamin D>20 and WT+. In difficult to treat HCV genotypes the proportion of patients achieving SVR significantly increased with a linear trend from the first to the last group: 6/25 (24.0%), 9/24 (37.5%), 12/29 (41.4%), 19/29 (65.5%) (p=0.003). At multivariate analysis having basal vitamin D >20 ng/mL plus the carriage of GC WT+ was found to be an independent predictor of SVR (O.R. 4.52, p=0.015). Conclusions: in difficult to treat HCV genotypes, simultaneous pre treatment normal serum vitamin D levels and the carriage of GCglobulin wild type isoform strongly predicts the achievement of SVR after PEG-interferon plus ribavirin antiviral therapy. Page 3 of 28 Hepatolog

Trends in chronic hepatitis B virus infection in Italy over a 10-year period: Clues from the nationwide PITER and MASTER cohorts toward elimination

Objectives: The study measures trends in the profile of patients with chronic hepatitis B virus linked to care in Italy. Methods: A cross-sectional, multicenter, observational cohort (PITER cohort) of consecutive patients with hepatitis B surface antigen (HBsAg) over the period 2019-2021 from 46 centers was evaluated. The reference was the MASTER cohort collected over the years 2012-2015. Standard statistical methods were used. Results: The PITER cohort enrolled 4583 patients, of whom 21.8% were non-Italian natives. Compared with those in MASTER, the patients were older and more often female. The prevalence of hepatitis B e antigen (HBeAg) declined (7.2% vs 12.3; P <0.0001) and that of anti-hepatitis D virus (HDV) remained stable (9.3% vs 8.3%). In both cohorts, about 25% of the patients had cirrhosis, and those in the PITER cohort were older. HBeAg-positive was 5.0% vs 12.6% (P <0.0001) and anti-HDV positive 24.8% vs 17.5% (P <0.0017). In the logistic model, the variables associated with cirrhosis were anti-HDV-positive (odds ratio = 10.08; confidence interval 7.63-13.43), age, sex, and body mass index; the likelihood of cirrhosis was reduced by 40% in the PITER cohort. Among non-Italians, 12.3% were HBeAg-positive (vs 23.4% in the MASTER cohort; P <0.0001), and 12.3% were anti-HDV-positive (vs 11.1%). Overall, the adherence to the European Association for the Study of the Liver recommendations for antiviral treatment increased over time. Conclusion: Chronic hepatitis B virus infection appears to be in the process of becoming under control in Italy; however, HDV infection is still a health concern in patients with cirrhosis and in migrants

New organ allocation criteria in liver transplantation

Summary. The organ allocation modality in the liver transplant represents a fundamental step for the correct success of the transplantation procedure. The practical effects deriving from the adoption of the organ allocation models do not imply only clinical repercussions but also concern important ethical aspects. Alongside the general principles of fairness, justice and transparency, the organ allocation models should be aimed at providing for each patient who waits for an organ, the possibility of accessing it, preserving and maximizing the outcome of the transplant in terms of survival and quality of life. Balancing successfully the clinical and ethical aspects in an allocation model is particularly difficult and probably not completely feasible. In this brief review, the general principles governing the different models of organ allocation in liver transplantation are addressed. A particular description of the decision-making process that led to the sharing in Italy of a new allocation model based on the concept of the transplant benefit is illustrated. In this model we have tried to combine the two fundamental principles that for many years have guided the choice of allocation models, respectively based on the criteria of urgency and utility

13 kA Superconducting Busbars Manufacturing Process

In the LHC, the superconducting Main Bending magnets and Quadrupole magnets are series-connected electrically in different excitation circuits by means of superconducting busbars, carrying a maximum current of 13 kA. These superconducting busbars consist of a superconducting Rutherford cable thermally and electrically coupled to a copper section all along the length. The function of the copper section is essentially to provide an alternative path for the magnet current in case of resistive transition. The production of these components was originally outsourced. The decision to import the technology at CERN led to a global re-engineering of the standard process. Although based on the procedures adopted during the LHC construction, a few modifications and improvements have been implemented, profiting of the experience gained in the last few years. This document details the manufacturing process of the 13 kA busbars as it is actually performed at CERN, emphasizing the new solutions adopted during the first months of production

Challenges and future developments in liver transplantation

Liver transplantation (LTLT) has become the treatment of choice for a wide range of liver diseases in both adult and pediatric patients. Until recently, the largest proportion of LTLT in adults, were performed in patients with hepatitis C (HCV) related cirrhosis. The recent availability of safe and effective direct antiviral agents to cure HCV infection in almost all patients whatever the HCV genotype and severity of liver disease, will reduce the need for LTLT in this category of recipients. Thus, it is presumed that in the next 1 to 2 decades HCV related liver disease will diminish substantially, whereas non-alcoholic steato-hepatitis (NAS H) will correspondingly escalate as an indication for LTLT. The greatest challenges facing LTLT remain the limited supply of donor organs, and the need for chronic immunosuppression, which represent the true obstacles to the greater application and durable success of the LTLT procedure. This review aimed to highlight, in different sections, the main open issues and future developments in LTLT. These will be focused to explore current and future strategies to maximize the use of limited organs, to offer an update on potential new approaches to immunosuppression and to imagine new indications for LTLT when the number of patients awaiting transplants for HCV related liver disease is reduced

Poroviscoelastic characterization of particle-reinforced gelatin gels using indentation and homogenization.

Hydrogels are promising materials for bioengineering applications, and are good model materials for the study of hydrated biological tissues. As these materials often have a structural function, the measurement of their mechanical properties is of fundamental importance. In the present study gelatin gels reinforced with ceramic microspheres are produced and their poroviscoelastic response in spherical indentation is studied. The constitutive responses of unreinforced gels are determined using inverse finite element modeling in combination with analytical estimates of material parameters. The behavior of composite gels is assessed by both analytical and numerical homogenization. The results of the identification of the constitutive parameters of unreinforced gels show that it is possible to obtain representative poroviscoelastic parameters by spherical indentation without the need for additional mechanical tests. The agreement between experimental results on composite gelatin and the predictions from homogenization modeling show that the adopted modeling tools are capable of providing estimates of the poroviscoelastic response of particle-reinforced hydrogels