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Efficacy and Safety of Daclatasvir in Hepatitis C: An Overview

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Journal of Clinical and Translational Hepatology 2016年第4期4卷 336-344页

作者： Nesrine Gamal stefano gitto Pietro Andreone Department of Medical and Surgical Sciences University of Bologna Bologna Italy

Hepatitis C virus (HCV) infection is a growing public health concern,with 184 million people infected *** the past decade,interferon has been the backbone of HCV treatment,even though it remains far from *** latest development of the new direct antivirals has drastically changed the treatment approach for chronic hepatitis C (CHC).Inhibitors of the HCV NS5A region have garnered remarkable interest among treating physicians,due to their high potency and favourable safety *** particular,treatment with daclatasvir (DCV) has yielded high rates of vriologic response in patients infected with genotype (Gt) 1 and Gt 3,when used in combination with other antivirals of a different class,such as *** few data are available for DCV treatment of the other Gts,the results in patients with Gt 2 and Gt 4 infection appear promising,as do those for unique patient ***5A-resistant viral variants can pre-exist or emerge after treatment failure for the HCV NS5A ***,DCV-resistant viral variants continue to be sensitive to interferon and other classes of antivirals such as NS3/4A and NS5B ***,we aimed to provide an overview of the current knowledge about DCV in the treatment of CHC.

关键词： Daclatasvir NS5A inhibitor Hepatitis C Direct antivirals New antiviral therapy

Stem cells for end stage liver disease: How far have we got?

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World Journal of Gastroenterology 2008年第29期14卷 4593-4599页

作者： Stefania Lorenzini stefano gitto Elena Grandini Pietro Andreone Mauro Bernardi Dipartimento di Medicina Clinica. Unità Operativa di Semeiotica Medica. University of Bologna Italy

End stage liver disease (ESLD) is a health problem worldwide. Liver transplantation is currently the only effective therapy, but its many drawbacks include a shortage of donors, operative damage, risk of rejection and in some cases recidivism of the pre-transplant disease. These factors account for the recent growing interest in regenerative medicine. Experiments have sought to identify an optimal source of stem cells, sufficient to generate large amounts of hepatocytes to be used in bioartificial livers or injected in vivo to repair the diseased organ. This update aims to give non-stem cell specialists an overview of the results obtained to date in this fascinating field of biomedical research.

关键词： End stage liver disease Liver failuretreatment Stem cells Regenerative medicine

Hepatocellular carcinoma and liver transplant: beyond the Milan criteria and the risk of "short-blanket" syndrome

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Hepatobiliary Surgery and Nutrition 2020年第4期9卷 518-521页

作者： stefano gitto stefano Di Sandro Paolo Magistri Pietro Andreone Fabrizio Di Benedetto Department of Experimental and Clinical Medicine University of FlorenceFlorenceItaly Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit AOU di Modena and University of Modena and Reggio EmiliaModenaItaly Internal and Metabolic Medicine AOU di Modena and University of Modena and Reggio EmiliaModenaItaly

Liver transplant(LT)is considered the best option for patients with hepatocellular carcinoma(HCC)confined into the liver and generally associated with liver cirrhosis(1).The Milan criteria(MC)represent a milestone in the selection of these patients(2).Therefore,basing on MC,the 5-year survival rate after LT could increase to 70%,with a HCC recurrence rate lower than 10%(2).Despite that,too many patients affected by HCC may not benefit from LT due to a tumor stage beyond the selection *** the last two decades,authors and physicians tried to overcome the MC exploring the opportunity to safely transplant patients beyond(3).Notably,the donor shortage and the competition between patients listed due to HCC and those listed for other indications,force physicians in selecting candidates with the best transplant benefit(3).

关键词： beyond listed overcome

Update on Alcohol and Viral Hepatitis

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Journal of Clinical and Translational Hepatology 2014年第4期2卷 228-233页

作者： stefano gitto Giovanni Vitale Erica Villa Pietro Andreone Dipartimento di Gastroenterologia Azienda Ospedaliero-Universitaria&University of Modena and Reggio Emilia Modena Italy Dipartimento di Scienze Mediche e Chirurgiche University of Bologna and Dipartimento dell'Apparato Digerente Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant'Orsola Malpighi Bologna Italy

Alcohol consumption is often associated with viral hepatitis. Although alcohol is known to worsen viral liver disease, the interactions between alcohol and viral hepatitis are not fully understood. Molecular alterations in the liver due to alcohol and viral hepatitis include effects on viral replication, increased oxidative stress, cytotoxicity, and a weakened immune response. Clinically, alcohol enhances disease pro-gression and favors induction of primitive liver neoplasm. The use of new antivirals for hepatitis C and well-established drugs for hepatitis B will determine how viral hepatitis can be controlled in a large percentage of these patients. However, alcohol-related liver disease continues to represent a barrier for access to antivirals, and it remains an unresolved health issue.

关键词： Alcohol HBV HCV

Microbiota and viral hepatitis:State of the art of a complex matter

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World Journal of Gastroenterology 2021年第33期27卷 5488-5501页

作者： Ivana Milosevic Edda Russo Ankica Vujovic Aleksandra Barac Olja Stevanovic stefano gitto Amedeo Amedei Clinic for Infectious and Tropical Diseases Clinical Centre of Serbia Faculty of MedicineUniversity of BelgradeBelgrade 101801Serbia Department of Experimental and Clinical Medicine University of FlorenceFirenze 50100Italy

Changes in gut microbiota influence both the gut and liver,which are strictly connected by the so-called“gut-liver axis”.The gut microbiota acts as a major determinant of this relationship in the onset and clinical course of liver *** to the results of several studies,gut dysbiosis is linked to viral hepatitis,mainly hepatitis C virus and hepatitis B virus *** bacteriaderived metabolites and cellular components are key molecules that affect liver function and modulate the pathology of viral *** studies showed that the gut microbiota produces various molecules,such as peptidoglycans,lipopolysaccharides,DNA,lipoteichoic acid,indole-derivatives,bile acids,and trimethylamine,which are translocated to the liver and interact with liver immune cells causing pathological ***,the existence of crosstalk between the gut microbiota and the liver and its implications on host health and pathologic status are essential factors impacting the etiology and therapeutic *** mechanisms behind the pathogenic role of gut-derived components on the pathogenesis of viral hepatitis remain unclear and not *** this review,we discuss the current findings of research on the bidirectional relationship of the components of gut microbiota and the progression of liver diseases and viral hepatitis and vice ***,this paper highlights the current therapeutic and preventive strategies,such as fecal transplantation,used to restore the gut microbiota composition and so improve host health.

关键词： Gut microbiota Hepatitis B virus Hepatitis C virus Liver diseases,Fecal transplantation

Coffee, Traditional Chinese Medicine and cannabinoids as potential tools for prevention and treatment of hepatocellular carcinoma

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Hepatoma Research 2016年第1期2卷 71-77页

作者： stefano gitto Ranka Vukotic Pietro Andreone Department of Gastroenterology Azienda Ospedaliero-Universitaria and University of Modena and Reggio Emilia41124 ModenaItaly Department of Medical and Surgical Sciences University of Bologna and Azienda Ospedaliero-Universitaria di BolognaPoliclinico Sant’Orsola Malpighi40138 BolognaItaly

In the last decade,the incidence of hepatocellular carcinoma(HCC)is growing in both Europe and United *** therapies such as liver resection,transplantation,ablation,chemoembolization and sorafenib are not enough to avoid a significant *** studies suggested the positive effect of caffeine for prevention of ***,the amount of therapeutic caffeine and the high-dose safety are *** authors proposed Traditional Chinese Medicine as preventive and/or curative *** it reveals limits such as the uncertain safety profile and the lack of evidence about a unique product,it shows interesting results in terms of survival and quality of life if given in combination with standard loco-regional *** the future promises,cannabinoids show interesting background mechanisms of blocking cell proliferation and *** is conceivable that in the next years,some natural products may have a role in improving the standards of care of HCC.

关键词： Hepatocellular carcinoma caffeine Traditional Chinese Medicine cannabinoids

Hepatitis C virus recurrence after liver transplantation:A 10-year evaluation

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World Journal of Gastroenterology 2015年第13期21卷 3912-3920页

作者： stefano gitto Luca Saverio Belli Ranka Vukotic Stefania Lorenzini Aldo Airoldi Arrigo Francesco Giuseppe Cicero Marcello Vangeli Lucia Brodosi Arianna Martello Panno Roberto Di Donato Matteo Cescon Gian Luca Grazi Luciano De Carlis Antonio Daniele Pinna Mauro Bernardi Pietro Andreone Department of Medical and Surgical Sciences University of Bologna and Azienda Ospedaliero-Universitaria di BolognaPoliclinico Sant’Orsola Malpighi40138 BolognaItaly Department of Gastroenterology Azienda Ospedaliero-Universitaria and University of Modena and Reggio Emilia41124 ModenaItaly Department of Hepatology and Gastroenterology Niguarda Hospital20162 MilanItaly Hepatobiliopancreatic and General Surgery Unit Regina Elena Institute00186 RomeItaly Department of General Surgery and Transplantation Niguarda Hospital20162 MilanItaly

AIM: To evaluate the predictors of 10-year survival of patients with hepatitis C recurrence. METHODS: Data from 358 patients transplanted between 1989 and 2010 in two Italian transplant centers and with evidence of hepatitis C recurrence were analyzed. A χ2, Fisher's exact test and Kruskal Wallis' test were used for categorical and continuous variables, respectively. Survival analysis was performed at 10 years after transplant using the Kaplan-Meier method, and a log-rank test was used to compare groups. A P level less than 0.05 was considered significant for all tests. Multivariate analysis of the predictive role of different variables on 10-year survival was performed by a stepwise Cox logistic ***: The ten-year survival of the entire population was 61.2%. Five groups of patients were identified according to the virological response or lack of a response to antiviral treatment and, among those who were not treated, according to the clinical status(mild hepatitis C recurrence, "too sick to be treated" and patients with comorbidities contraindicating the treatment). While the 10-year survival of treated and untreated patients was not different(59.1% vs 64.7%, P = 0.192), patients with a sustained virological response had a higher 10-year survival rate than both the "non-responders"(84.7% vs 39.8%, P < 0.0001) and too sick to be treated(84.7% vs 0%, P < 0.0001). Sustained virological responders had a survival rate comparable to patients untreated with mild recurrence(84.7% vs 89.3%). A sustained virological response and young donor age were independent predictors of 10-year survival. CONCLUSION: Sustained virological response significantly increased long-term survival. Awaiting the interferon-free regimen global availability, antiviral treatment might be questionable in selected subjects with mild hepatitis C recurrence.

关键词： Hepatitis C Liver transplantation Hepatitis C viru

Incoherent non-Hermitian skin effect in photonic quantum walks

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Light(Science & Applications) 2024年第5期13卷 885-893页

作者： stefano Longhi Dipartimento di Fisica Politecnico di MilanoPiazza L.da Vinci 32I-20133 MilanoItaly IFISC(UIB-CSIC) Instituto de Fisica Interdisciplinar y Sistemas ComplejosE-07122 Palma de MallorcaSpain

The non-Hermitian skin effect describes the concentration of an extensive number of eigenstates near the boundaries of certain dissipative *** phenomenon has raised a huge interest in different areas of physics,including photonics,deeply expanding our understanding of non-Hermitian systems and opening up new avenues in both fundamental and applied aspects of topological *** skin effect has been associated to a nontrivial pointgap spectral topology and has been experimentally demonstrated in a variety of synthetic matter systems,including photonic *** most of physical models exhibiting the non-Hermitian skin effect full or partial wave coherence is generally *** we push the concept of skin effect into the fully incoherent regime and show that rather generally(but not universally)the non-Hermitian skin effect persists under dephasing *** results are illustrated by considering incoherent light dynamics in non-Hermitian photonic quantum walks.

关键词： dynamics. quantum effect

Time reversal of a discrete system coupled to a continuum based on non-Hermitian flip

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Science Bulletin 2017年第12期62卷 869-874页

作者： stefano Longhi Dipartimento di Fisica Politecnico di Milano and Istituto di Fotonica e Nanotecnologie del Consiglio Nazionale delle RicerchePiazza L.da Vinci 321-20133 MilanoItaly

Time reversal in quantum or classical systems described by an Hermitian Hamiltonian is a physically allowed process, which requires in principle inverting the sign of the Hamiltonian. Here we consider the problem of time reversal of a subsystem of discrete states coupled to an external environment characterized by a continuum of states, into which they generally decay. It is shown that, by flipping the discrete-continuum coupling from an Hermitian to a non-Hermitian interaction, thus resulting in a non unitary dynamics, time reversal of the subsystem of discrete states can be achieved, while the continuum of states is not reversed. Exact time reversal requires frequency degeneracy of the discrete states,or large frequency mismatch among the discrete states as compared to the strength of indirect coupling mediated by the continuum. Interestingly, periodic and frequent switch of the discrete-continuum coupling results in a frozen dynamics of the subsystem of discrete states.

关键词： Non-Hermitian dynamicsTime reversalLoschmidt echo