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Hepatitis C virus reinfection after liver transplantation: Is there a role for direct antiviral agents?

World Journal of Gastroenterology 2014年第28期20卷 9253-9260页

作者： Marco Dall’Agata Annagiulia Gramenzi Maurizio Biselli mauro bernardi Semeiotica Medica - Policlinico S.Orsola-Malpighi Dipartimento di Scienze Mediche e ChirurgicheUniversity of Bologna

Recurrence of hepatitis C virus(HCV)infection following liver transplantation(LT)is almost universal and can accelerate graft cirrhosis in up to 30%of *** development of effective strategies to treat or prevent HCV recurrence after LT remains a major challenge,considering the shortage of donor organs and the accelerated progression of HCV in LT *** antiviral therapy with pegylated-interferon plus ribavirin is the current treatment of choice for HCV LT recipients,even though the combination is not as effective as it is in immunocompetent patients.A sustained virological response in the setting of LT improves patient and graft survival,but this is only achieved in 30%-45%of patients and the treatment is poorly *** improve the efficacy of pre-and post-transplant antiviral therapy,a new class of potent direct-acting antiviral agents (DAAs)has been *** aim of this review is to summarize the use of DAAs in LT HCV ***,Cochrane Library,MEDLINE,EMBASE,Web of Science and clinical trial databases were searched for this *** date,only three clinical studies on the topic have been published and most of the available data are in abstract *** a moderately successful early virological response has been reported,DAA treatment regimens were associated with severe toxicity mitigating their potential ***,the ongoing nature of data,the lack of randomized studies,the small number of enrolled patients and the heterogeneity of these studies make the results largely anecdotal and *** conclusion,large welldesigned clinical studies on DAAs in HCV LT patients are required before these drugs can be recommended after transplantation.

关键词： Hepatitis C virus Liver transplantation Direct antiviral agents Peginterferon/ribavirin Immunosuppressive agents

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Robust estimation of time-dependent precision matrix with application to the cryptocurrency market

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Financial Innovation 2022年第1期8卷 1313-1337页

作者： Paola Stolfi mauro bernardi Davide Vergni Institute for Applied Mathematics“mauro Picone”(IAC)-National Research Council of Italy Via dei Taurini 1900185 RomeItaly Department of Statistical Sciences University of PadovaVia C.Battisti24135121 PaduaItaly

Most financial signals show time dependency that,combined with noisy and extreme events,poses serious problems in the parameter estimations of statistical ***,when addressing asset pricing,portfolio selection,and investment strategies,accurate estimates of the relationship among assets are as necessary as are delicate in a time-dependent *** this regard,fundamental tools that increasingly attract research interests are precision matrix and graphical models,which are able to obtain insights into the joint evolution of financial *** this paper,we present a robust divergence estimator for a time-varying precision matrix that can manage both the extreme events and time-dependency that affect financial time ***,we provide an algorithm to handle parameter estimations that uses the“maximization–minimization”*** apply the methodology to synthetic data to test its ***,we consider the cryptocurrency market as a real data application,given its remarkable suitability for the proposed method because of its volatile and unregulated nature.

关键词： Time-varying models Robust methods Kernel estimation Precision matrix Divergence

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Bone marrow derived stem cells for the treatment of end-stage liver disease

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World Journal of Gastroenterology 2014年第27期20卷 9098-9105页

作者： Cristina Margini Ranka Vukotic Lucia Brodosi mauro bernardi Pietro Andreone Dipartimento di Scienze mediche e Chirurgiche Unità Operativa di Semeiotica Medica University of Bologna

End-stage disease due to liver cirrhosis is an important cause of death worldwide. Cirrhosis results from progressive, extensive fibrosis and impaired hepatocyte regeneration. The only curative treatment is liver transplantation, but due to the several limitations of this procedure, the interest in alternative therapeutic strategies is increasing. In particular, the potential of bone marrow stem cell(BMSC) therapy in cirrhosis has been explored in different trials. In this article, we evaluate the results of 18 prospective clinical trials, and we provide a descriptive overview of recent advances in the research on hepatic regenerative medicine. The main message from the currently available data in the literature is that BMSC therapy is extremely promising in the context of liver cirrhosis. However, its application should be further explored in randomized, controlled trials with large cohorts and long follow-ups.

关键词： Liver cirrhosis Liver regeneration Hematopoietic stem cells Mesenchymal stem cells End stage liver disease

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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

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Ketoprofen,peginterferon 2a and ribavirin for genotype 1 chronic hepatitis C:A phaseⅡ study

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World Journal of Gastroenterology 2009年第47期15卷 5946-5952页

作者： Annagiulia Gramenzi Carmela Cursaro Marzia Margotti Clara Balsano Alessandra Spaziani Simona Anticoli Elisabetta Loggi Maddalena Salerno Silvia Galli Giuliano Furlini mauro bernardi Pietro Andreone Department of Clinical Medicine University of Bologna40138 Bologna Italy Molecular Virology and Oncology Laboratory "A.Cesalpino" FoundationUniversity of Rome"La Sapienza"00161 Rome Italy Department of Internal Medicine University of L'Aquila67100 L'AquilaItaly Hepatology Outpatient Clinic Hospital of Paola87027 Paola(CS)Italy Department of Hematology Oncology and Laboratory MedicineS.Orsola-Malpighi Hospital40138 BolognaItaly

AIM:To evaluate the safety of adding ketoprofen to pegylated-interferon(PEG-IFN)with or without ribavirin and the effect on viral kinetics,STAT1 activity and expression of 2'-5'-oligoadenylate synthetase (2'-5'OAS)in genotype 1 chronic hepatitis C in a phaseⅡstudy. METHODS:Forty-five patients were studied:fifteen were randomized to PEG-IFN plus ribavirin(PR),16 to PEGIFN plus ketoprofen and 14 to PR and *** study of IFN-dependent signal transduction was conducted in 9 patients from each group. RESULTS:The combination of ketoprofen and PEG- IFN with or without ribavirin was safe and well *** early activation of STAT1 was observed in ke-toprofen-treated patients,but this activation was less sustained over ***,ketoprofen plus PEG- IFN and ribavirin induced an early and sustained increase of 2'-5'OAS transcription starting 24 h after the first dose until the 36th *** data are consistent with the clinical results,showing a better sustained virological response and a lower relapse rate in patients receiving ketoprofen plus PEG-IFN and ribavirin. CONCLUSION:The addition of ketoprofen to the standard therapy of chronic hepatitis C should be explored in larger randomized clinical studies.

关键词： Liver Viral hepatitis Chronic hepatitis C Clinical pharmacology Non-steroidal antiinflammatory drugs

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How albumin administration for cirrhosis impacts on hospital albumin consumption and expenditure

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World Journal of Gastroenterology 2011年第30期17卷 3479-3486页

作者： Federica Mirici-Cappa Paolo Caraceni Marco Domenicali Ernesto Gelonesi Barbara Benazzi Giacomo Zaccherini Franco Trevisani Cristina Puggioli mauro bernardi Department of Clinical Medicine Alma MaterS tudiorumUniversity of Bologna40126 BolognaItaly UO Pharmacology S Orsola-Malpighi University Hospital40138 BolognaItaly

AIM:To assess the impact of guidelines for albumin prescription in an academic hospital,which is a referral center for liver ***:Although randomized trials and guidelines support albumin administration for some complications of cirrhosis,the high cost of albumin greatly limits its use in clinical *** 2003,a multidisciplinary panel at Sant'Orsola-Malpighi University Hospital(Bologna,Italy)used a literature-based consensus method to list all the acute and chronic conditions for which albumin is indicated as first-or second-line *** in hepatology included prevention of post-paracentesis circulatory dysfunction and renal failure induced by spontaneous bacterial peritonitis,and treatment of hepatorenal syndrome and refractory *** still debated,albumin administration in refractory ascites is accepted by the Italian health care *** analyzedalbumin prescription and related costs before and after implementation of the new ***:While albumin consumption and costs doubled from 1998 to 2002,they dropped 20%after 2003,and remained stable for the following 6 *** of cirrhosis,namely refractory ascites and paracentesis,represented the predominant indications,followed by major surgery,shock,enteric diseases,and *** consumption increased significantly after guideline implementation in the liver units,whereas it declined elsewhere in the ***,extra-protocol albumin prescription was estimated as<10%.CONCLUSION:Albumin administration in cirrhosis according to international guidelines does not increase total hospital albumin consumption if its use in settings without evidence of efficacy is avoided.

关键词： Human serum albumin Cost analysis Livercirrhosis Critical illness Ascites

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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

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Cryoglobulinemia in elderly patients with HCV-related chronic hepatitis

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2010年第2期1卷 72-74页

作者： Francesco Giuseppe Foschi Anna Chiara Dall'Aglio Arianna Lanzi Giorgio Marano Sara Savini Pietro Andreone mauro bernardi Giuseppe Francesco Stefanini Department of Internal Medicine Faenza Hospital Department of Clinical Medicine Bologna University

Hepatitis C virus(HCV) infection affects about 3% of the world's population and often leads to chronic liver *** some industrialized countries,HCV prevalence increases with age,but the optimal management of older patients has not been accurately *** infection can also lead to lymphoproliferative disorders,the most common being mixed cryoglobulinemia(MC),and also for this condition that frequently affects elderly patients,the optimal therapeutic strategy is still *** report the case of a 77-year-old Caucasian woman with HCV-related chronic hepatitis and cutaneous manifestations consisting of urticaria and pruritus related to MC resistant to *** patient underwent a treatment with interferon and *** a treatment led to early biochemical and virological response associated with the resolution of cryoglobulinemia and cutaneous *** the end of treatment,HCV replication relapsed,but cryoglobulinemia and cutaneous symptoms did not *** the absence of definite treatment guidelines in this particular context,our experience suggests that the presence of symptoms related to HCV-infection that deeply affect patient quality of life warrants antiviral therapy even beyond the age limits that currently exclude patients from treatment.

关键词： Cryoglobulinemia Elderly patients Hepatitis C virus chronic hepatitis Antiviral treatment

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