Long-term outcomes of direct acting antivirals in post-transplant advanced hepatitis C virus recurrence and fibrosing cholestatic hepatitis.

Long-term functional outcomes of sofosbuvir-based antiviral treatment were evaluated in a cohort study involving 16 Italian centres within the international compassionate use programme for post-transplant hepatitis C virus (HCV) recurrence. Seventy-three patients with cirrhosis (n=52) or fibrosing cholestatic hepatitis (FCH, n=21) received 24-week sofosbuvir with ribavirin\ub1pegylated interferon or interferon-free sofosbuvir-based regimen with daclatasvir/simeprevir+ribavirin. The patients were observed for a median time of 103 (82-112) weeks. Twelve of 73 (16.4%) died (10 non-FCH, 2 FCH) and two underwent re-LT. Sustained virological response was achieved in 46 of 66 (69.7%): 31 of 47 (66%) non-FCH and 15 of 19 (79%) FCH patients. All relapsers were successfully retreated. Comparing the data of baseline with last follow-up, MELD and Child-Turcotte-Pugh scores improved both in non-FCH (15.3\ub16.5 vs 10.5\ub13.8, P<.0001 and 8.4\ub12.1 vs 5.7\ub11.3, P<.0001, respectively) and FCH (17.3\ub15.9 vs 10.1\ub12.8, P=.001 and 8.2\ub11.6 vs 5.5\ub11, P=.001, respectively). Short-treatment mortality was higher in patients with baseline MELD 6525 than in those with MELD<25 (42.9% vs 4.8%, P=.011). Long-term mortality was 53.3% among patients with baseline MELD 6520 and 7.5% among those with MELD<20 (P<.0001). Among deceased patients 75% were Child-Turcotte-Pugh class C at baseline, while among survivors 83.9% were class A or B (P<.0001). Direct acting antivirals-based treatments for severe post-transplant hepatitis C recurrence, comprising fibrosing cholestatic hepatitis, significantly improve liver function, even without viral clearance and permit an excellent long-term survival. The setting of severe HCV recurrence may require the identification of "too-sick-to-treat patients" to avoid futile treatments

Timing for treatment of HCV recurrence after liver transplantation: the earlier the better.

HCV is the leading cause of death from liver disease and is the most common indication for a liver transplantation. Although HCV is a widespread health problem, disease management is particularly challenging in several key subpopulations, including liver transplant recipients. HCV recurrence after liver transplantation constituted a major challenge for the physicians during the last years. The recommended standard of care before the advent of new regimen was the treatment of confirmed recurrent disease, based either on persistent, unexplained elevated alanine aminotransferase levels or on histologically confirmed fibrosis, once rejection, biliary obstruction, and vascular damage have been ruled out. Moreover, early therapy (including interferon) has been associated with high rates of adverse effects, an increased risk of graft rejection, and higher proportions of patients requiring dose reductions. We are now facing a "new era" of direct antiviral agents that is already changing the approach to HCV burden in the post liver transplantation setting. Available data on treatment of HCV recurrence with the new antiviral drugs showed sustained virological response that ranges between 60 to 100%. In this comment we have focused on both the utility of non invasive test to evaluate the fibrosis progression and on timing of antiviral therapy for HCV recurrence. This article is protected by copyright. All rights reserved

New Perspectives on Treatment of Hepatitis B Before and After Liver Transplantation

open5noThe hepatitis B virus (HBV) infects more than 260 million people globally, with increasing incidence, especially in developing countries. Despite antiviral therapies, HBV-related end-stage liver disease remains one of the most important indications for liver transplantation worldwide. Although new available treatments have improved the outcome of patients with both compensated and decompensated liver disease in some specific clinical settings as acute-on-chronic liver failure mortality is still high. Moreover, the incidence of HBV-related hepatocellular carcinoma (HCC) seems to be increasing and represents a major challenge for the transplant team. In the post-transplant setting, combination of anti-HBV immunoglobulins and oral nucleos(t)ides provided significant improvement on graft and patient survival. Furthermore, recent data suggested the possibility of personalized therapeutic algorithms based on pre and post-transplant viral and host risk factors. Finally, liver grafts from HBV core antibody (anti-HBc) positive or hepatitis B surface antigen (HBsAg) donors can be safely used in order to expand the donor pool, considering adequate allocation and tailored prophylaxis after LT. In this review we have focused on the evolution of antiviral therapy for HBV, highlighting useful information to aid the transplant hepatologist in clinical practice.ReviewopenZanetto, Alberto; Ferrarese, Alberto; Bortoluzzi, Ilaria; Burra, Patrizia; Russo, Francesco PaoloZanetto, Alberto; Ferrarese, Alberto; Bortoluzzi, Ilaria; Burra, Patrizia; Russo, FRANCESCO PAOL

Emotional Reactions to the Perception of Risk in the Pompeii Archaeological Park

The assessment of perceived risk by people is extremely important for safety and security management. Each person is based on the opinion of others to make a choice and the Internet represents the place where these opinions are mostly researched, found and reviewed. Social networks have a decisive impact: 92% of consumers say they have more trust in social media reviews than in any other form of advertising. For this reason, Opinion Mining and Sentiment Analysis have found interesting applications in the most diverse context, among which the most innovative is certainly represented by public safety and security. Security managers can use the perceptions expressed by people to discover the unexpected and potential weaknesses of a controlled environment or otherwise the risk and security perception of people that sometimes can be very different from real level of risk and security of a given site. Since the perceptions are the result of mostly unconscious elaborations, it is necessary to go deeper and to search for the emotions, triggered by the sensorial stimuli, that determine them. The objective of this paper is to study the perception of risk within the Pompeii Archaeological Park, giving emphasis to the emotional components, using the semantic analysis of the textual contents present in Twitter.Peer reviewe

Heparanase and macrophage interplay in the onset of liver fibrosis

Abstract The heparan sulfate endoglycosidase heparanase (HPSE) is involved in tumor growth, chronic inflammation and fibrosis. Since a role for HPSE in chronic liver disease has not been demonstrated to date, the current study was aimed at investigating the involvement of HPSE in the pathogenesis of chronic liver injury. Herein, we revealed that HPSE expression increased in mouse livers after carbon tetrachloride (CCl4)-mediated chronic induction of fibrosis, but with a trend to decline during progression of the disease. In mouse fibrotic liver tissues HPSE immunostaining was restricted in necro-inflammatory areas, co-localizing with F4/80 macrophage marker and TNF-α. TNF-α treatment induced HPSE expression as well as HPSE secretion in U937 macrophages. Moreover, macrophage-secreted HPSE regulated the expression of α-SMA and fibronectin in hepatic stellate LX-2 cells. Finally, HPSE activity increased in the plasma of patients with liver fibrosis but it inversely correlated with liver stiffness. Our results suggest the involvement of HPSE in early phases of reaction to liver damage and inflammatory macrophages as an important source of HPSE. HPSE seems to play a key role in the macrophage-mediated activation of hepatic stellate cells (HSCs), thus suggesting that HPSE targeting could be a new therapeutic option in the treatment of liver fibrosis

Role of antiviral therapy in the natural history of hepatitis B virus-related chronic liver disease

Hepatitis B virus (HBV) infection is a dynamic state of interactions among HBV, hepatocytes, and the host immune system. Natural history studies of chronic hepatitis B (CHB) infection have shown an association between active viral replication and adverse clinical outcomes such as cirrhosis and hepatocellular carcinoma. The goal of therapy for CHB is to improve quality of life and survival by preventing progression of the disease to cirrhosis, decompensation, end-stage liver disease, hepatocellular carcinoma (HCC) and death. This goal can be achieved if HBV replication is suppressed in a sustained manner. The accompanying reduction in histological activity of CHB lessens the risk of cirrhosis and of HCC, particularly in non-cirrhotic patients. However, CHB infection cannot be completely eradicated, due to the persistence of covalently closed circular DNA in the nucleus of infected hepatocytes, which may explain HBV reactivation. Moreover, the integration of the HBV genome into the host genome may favour oncogenesis, development of HCC and may also contribute to HBV reactivation

Markers of acute rejection and graft acceptance in liver transplantation.

The evaluation of the immunosuppression state in liver transplanted patients is crucial for a correct post-transplant management and a major step towards the personalisation of the immunosuppressive therapy. However, current immunological monitoring after liver transplantation relies mainly on clinical judgment and on immunosuppressive drug levels, without a proper assessment of the real suppression of the immunological system. Various markers have been studied in an attempt to identify a specific indicator of graft rejection and graft acceptance after liver transplantation. Considering acute rejection, the most studied markers are pro-inflammatory and immunoregulatory cytokines and other proteins related to inflammation. However there is considerable overlap with other conditions, and only few of them have been validated. Standard liver tests cannot be used as markers of graft rejection due to their low sensitivity and specificity and the weak correlation with the severity of histopathological findings. Several studies have been performed to identify biomarkers of tolerance in liver transplanted patients. Most of them are based on the analysis of peripheral blood samples and on the use of transcriptional profiling techniques. Amongst these, NK cell-related molecules seem to be the most valid marker of graft acceptance, whereas the role CD4+CD25+Foxp3+ T cells has still to be properly defined

Verso la tecnologia 6G per i luoghi della cultura

Considering the remarkable historical, artistic, monumental, demoethno-anthropological, archaeological, archival and national library heritage, in order to improve the management and safety of places of culture, it becomes essential to focus attention on the new 6G technology which will allow the fusion of digital world with the physical world capable of transmitting huge amounts of data and information in seconds. The places of culture (archaeological areas, archaeological parks, museums, monuments, archives, libraries), like other built places, thanks to 6G technology and its flexibility, versatility, sustainability, reliability, will be able to become completely interconnected

Hepatitis C virus related cirrhosis decreased as indication to liver transplantation since the introduction of direct-acting antivirals: A single-center study

AIM: To evaluate waiting list (WL) registration and liver transplantation (LT) rates in patients with hepatitis C virus (HCV)-related cirrhosis since the introduction of direct-acting antivirals (DAAs). METHODS: All adult patients with cirrhosis listed for LT at Padua University Hospital between 2006-2017 were retrospectively collected using a prospectively-updated database; patients with HCV-related cirrhosis were divided by indication for LT [dec-HCV vs HCV/ hepatocellular carcinoma (HCC)] and into two interval times (2006-2013 and 2014-2017) according to the introduction of DAAs. For each patient, indications to LT, severity of liver dysfunction and the outcome in the WL were assessed and compared between the two different time periods. For patients receiving DAA-based regimens, the achievement of viral eradication and the outcome were also evaluated. RESULTS: One thousand one hundred and ninty-four [male (M)/female (F): 925/269] patients were included. Considering the whole cohort, HCV-related cirrhosis was the main etiology at the time of WL registration (490/1194 patients, 41%). HCV-related cirrhosis significantly decreased as indication to WL registration after DAA introduction (from 43.3% in 2006-2013 to 37.2% in 2014-2017, P = 0.05), especially amongst dec-HCV (from 24.2% in 2006-2013 to 15.9% in 2014-2017, P = 0.007). Even HCV remained the most common indication to LT over time (289/666, 43.4%), there was a trend towards a decrease after DAAs introduction (from 46.3% in 2006-2013 to 39% in 2014-2017, P = 0.06). HCV patients (M/F: 43/11, mean age: 57.7 \ub1 8 years) who achieved viral eradication in the WL had better transplant-free survival (log-rank test P = 0.02) and delisting rate (P = 0.002) than untreated HCV patients. CONCLUSION: Introduction of DAAs significantly reduced WL registrations for HCV related cirrhosis, especially in the setting of decompensated cirrhosis

Verso la tecnologia 6G per i luoghi della cultura

Considering the remarkable historical, artistic, monumental, demoethno-anthropological, archaeological, archival and national library heritage, in order to improve the management and safety of places of culture, it becomes essential to focus attention on the new 6G technology which will allow the fusion of digital world with the physical world capable of transmitting huge amounts of data and information in seconds. The places of culture (archaeological areas, archaeological parks, museums, monuments, archives, libraries), like other built places, thanks to 6G technology and its flexibility, versatility, sustainability, reliability, will be able to become completely interconnected