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Hepatitis delta virus: From infection to new therapeutic strategies

World Journal of Gastroenterology 2021年第24期27卷 3530-3542页

作者： Grazia A Niro Arianna Ferro Francesca Cicerchia Isabella Brascugli marilena durazzo Department of Gastroenterology IRCCS Casa Sollievo della Sofferenza Hospital FoundationSan Giovanni Rotondo 71013Italy Department of Medical Sciences University of TurinTurin 10126Italy

The hepatitis delta virus(HDV)is a small RNA virus that encodes a single protein and which requires the hepatitis B virus(HBV)-encoded hepatitis B surface antigen(HBsAg)for its assembly and ***/HDV co-infections exist worldwide and show a higher prevalence among selected groups of HBV-infected populations,specifically intravenous drug users,practitioners of high-risk sexual behaviours,and patients with cirrhosis and hepatocellular *** chronic form of HDV-related hepatitis is usually severe and rapidly *** of the viral infection itself,including the status of co-infection or super-infection,virus genotypes(both for HBV and HDV),and persistence of the virus’replication,influence the outcome of the accompanying and manifested liver ***,disease severity is burdened by the lack of an effective cure for either virus *** decades,the main treatment option has been interferon,administered as mono-therapy or in combination with nucleos(t)ide *** its efficacy has been reported for different doses,durations and courses,only a minority of patients achieve a sustained response,which is the foundation of eventual improvement in related liver *** need for an efficient therapeutic alternative *** efforts towards this end have led to new treatment options that target specific steps in the HDV life cycle;the most promising among these are myrcludex B,which inhibits virus entry into hepatocytes,lonafarnib,which inhibits farnesylation of the viral-encoded LHDAg large hepatitis D antigen,and REP-2139,which interferes with HBsAg release and assembly.

关键词： Hepatitis delta virus Hepatitis B virus Myrcludex Lonafarnib REP 2139

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Autoimmune hepatitis treatment in the elderly: A systematic review

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World Journal of Gastroenterology 2019年第22期25卷 2809-2818页

作者： marilena durazzo Giulia Lupi Michela ScANDella Arianna Ferro Gabriella Gruden Department of Medical Sciences University of Turin

BACKGROUND Autoimmune hepatitis (AIH) is a rare chronic inflammatory liver disease with a high risk of progression to liver cirrhosis. The initial treatment for AIH usually includes a steroid, with or without azathioprine. AIH can present at any age;however, the most effective and safe induction treatment for AIH in the elderly remains unclear. AIM To systematically review available data on both effectiveness and safety of AIH treatments in elderly subjects. METHODS To identify studies on AIH induction treatment in elderly patients (≥ 60 years of age), an electronic research was performed (PubMed, EMBASE and Cochrane Library databases) until February 2019. Eligible studies were selected through screening of titles and abstracts, followed by full-text critical evaluation. After risk of bias assessment, data on study designs, interventions, and outcomes were extracted and reviewed. RESULTS Among the 1736 retrieved papers, 15 studies were selected. Out of them, eight studies were excluded because of a critical risk of bias. The remaining seven studies included 789 patients and out of them 239 subjects were elders. First-line treatment was a steroid either alone or in combination with azathioprine in most patients (87.6%) and only one study investigated the effect of combined steroid and mycophenolate mofetil therapy. Standard therapy was effective in inducing remission in the elderly. Moreover, treatment failure and relapses occurred less often in the elderly compared to younger *** Treatment of AIH is challenging in elderly patients. This systematic review confirms the efficacy and safety of standard induction treatment for AIH in the elderly. Available evidence is insufficient to draw any conclusion on the effect of novel AIH treatments in elderly subjects.

关键词： Autoimmune hepatitis Elderly patients Aged Steroids Azathioprine Mycophenolate mofetil

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Gender specific medicine in liver diseases:a point of view

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World Journal of Gastroenterology 2014年第9期20卷 2127-2135页

作者： marilena durazzo Paola Belci Alessandro Collo Vanessa Prandi Erika Pistone Maria Martorana Roberto Gambino Simona Bo Department of Medical Sciences University of Turin 10126 Turin Italy

Gender medicine focuses on the patho-physiological, clinical, prevention and treatment differences in diseases that are equally represented in men and women. The purpose of gender medicine is to ensure that each individual man and woman receives the best treatment possible based on scientific evidence. The concept of “gender” includes not only the sexual characteristics of individuals but also physiological and psychological attributes of men and women, including risk factors, protective/aggravating effects of sexual hormones and variances linked to genetics and corporal structures that explain biological and physiological differences between men and women. It is very important to consider all the biological, physiological, functional, psychological, social and cultural characteristics to provide patients with individualized disease management. Herein, we critically analyze the literature regarding gender differences for diseases and acquired conditions of the most representative hepatic pathologies: primary biliary cirrhosis, autoimmune hepatitis, primary sclerosing cholangitis, non alcoholic fatty liver disease and alcoholic liver disease, and viral chronic hepatitis B and C. The last section addresses hemochromatosis, which is a prevalent iron overload disorder in the Caucasian population. This review aims to describe data from the literature concerning viral chronic hepatitis during pregnancy, management during pregnancy and delivery, and new effective drugs for the prevention of maternal infection transmission without significant adverse effects or complications.

关键词： Gender Liver disease Primary biliary cirrhosis Autoimmune hepatitis Viral chronic hepatitis B Viral chronic hepatitis C Non alcoholic fatty liver disease Alcoholic liver disease

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Associations between y-glutamyl transferase, metabolic abnormalities and inflammation in healthy subjects from a population-based cohort: A possible implication for oxidative stress

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World Journal of Gastroenterology 2005年第45期11卷 7109-7117页

作者： Simona Bo Roberto Gambino marilena durazzo Sabrina Guidi Elisa Tiozzo Federica Ghione Luigi Gentile Maurizio Cassader Gian Franco Pagano Department of Internal Medicine Diabetic Clinic

AIM: To examine the relationships between γ -glutamyltransferase (GGT), alanine-aminotransferase (ALT),aspartate-aminotransferase (AST) and various metabolic parameters, C-reactive protein (CRP) and an oxidative stress marker (nitrotyrosine, NT) in subjects without any metabolic abnormalities from a population-based ***: Two hundred and five subjects with normal body mass index (BMI), glucose tolerance, and without any metabolic abnormality were studied out of 1339subjects, without known liver diseases, alcohol abuse or use of hepatotoxic drugs, who are representative of the 45-64 aged population of Asti (north-western Italy).RESULTS: In all patients metabolic parameters and hs-CRP levels linearly increase from the lowest to the highest ALT and GGT tertiles, while in subjects without metabolic abnormalities, there is a significant association between fasting glucose, uric acid, waist circumference,hs-CRP, triglyceride values, and GGT levels. In these subjects, male sex, higher hs-CRP and glucose levels are associated with GGT levels in a multiple regression model, after adjustments for multiple *** the same model, median NT levels are significantly associated with the increasing GGT tertile (β = 1.06;95%CI 0.67-1.45), but not with the AST and ALT *** a multiple regression model, after adjusting for age,sex, BMI, waist, smoking, and alcohol consumption, both NT (β = 0.05; 95%CI 0.02-0.08) and hs-CRP levels (β =0.09; 95%CI 0.03-0.15) are significantly associated with fasting ***: GGT, an easy, universally standardized and available measurement, could represent an early marker of sub-clinical inflammation and oxidative stress in otherwise healthy individuals. Prospective studies are needed to establish if GGT could predict future diabetes in these subjects.

关键词： Alanine aminotransferase Aspartate aminotransferase Body mass index C-reactive protein γ-Glutamyl transferase Metabolic syndrome Nitrotyrosine

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Lack of association between seroprevalence of Helicobacterpylori infection and primary biliary cirrhosis

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World Journal of Gastroenterology 2004年第21期10卷 3179-3181页

作者： marilena durazzo Floriano Rosina Alberto Premoli Enrico Morello Sharmila Fagoonee Rosaria Innarella Enrico Solerio Rinaldo Pellicano Mario Rizzetto Department of Internal Medicine Unitersity of TurinTurinItaly Department of Gastroenterology Gradenigo HospitalTurinltaly Department of Biology Biochemistry and GeneticsUniversity of TurinTurinltaly Department of Gastroenterology Molinette HospitalTurinltaly

AIM:To determine the association between seroprevalence of Helicobacter pylori(H pylori)infection and primary biliary cirrhosis(PBC). METHODS:In this case-control study,149 consecutive patients(10 males,139 females,mean age 58.2±11 years, range 26-82 years)suffering from PBC and 619 consecutive healthy volunteer blood donors(523 males,96 females, mean age 47±5.3 years,range 18-65 years)attending the Hospital Blood Bank and residing in the same area were recruited.A commercial enzyme linked immunosorbent assay was used to detect anti-H pylori(IgG)antibodies in serum. RESULTS:AnUbodies to Hpyloriwere present in 78(52.3%) out of 149 PBC-patients and in 291(47%)out of 619 volunteers(P=0.24,OR 1.24,95% CI 0.85-1.80).In the subjects less than 60 years old,the prevalence of H pylori infection among PBC-patients(40/79)was slightly higher than in controls(50.6% vs 46.2%)P=0.46,OR=1.19,95% CI:0.72-1.95).In those over 60 years,the prevalence of Hpylori infection was similar between PBC-patients and controls(54.2% vs57.8%,P=0.7,OR 0.86,95% CI 0.36- 2.07). CONCLUSION:There is no association between seroprevalence of H pylori in fection and primary biliary cirrhosis.

关键词： Adult Aged Aged, 80 and over Antibodies, Bacterial Case-Control Studies Female Helicobacter Infections Helicobacter pylori purification Humans Liver Cirrhosis, Biliary Male Middle Aged Research Support, Non-U.S. Gov't Seroepidemiologic Studies

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Alterations of seminal and hormonal parameters:An extrahepatic manifestation of HCV infection?

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World Journal of Gastroenterology 2006年第19期12卷 3073-3076页

作者： marilena durazzo Alberto Premoli Cataldo Di Bisceglie Angela Bertagna Emanuela Fagà Giampaolo Biroli Chiara Manieri Simona Bo Gianfranco Pagano Department of Internal Medicine University of Turin Italy Division of Endocrinology and Metabolic Diseases A.O.S.Giovanni Battista TurinItaly

AIM： To evaluate the possible influences of HCV infection and relative antiviral treatment on seminal parameters and reproductive hormonal serum levels. METHODS： Ten male patients with HCV-related chronic hepatitis and 16 healthy male volunteers were studied. In all subjects seminal parameters （nemaspermic concentration, progressive motility, morphology） and hormonal levels were determined. Seminal parameters and inhibin B, follicle-stimulating hormone, luteinizing hormone, total and free testosterone, estradiol, prolactine in patients were measured after six and twelve months of antiviral combined （interferon ± ribavirin） treatment. RESULTS： Patients before treatment showed a significantly lower nemaspermic motility and morphology as well as lower inhibin B and free testosterone levels than controls. Inhibin B levels in cases were improved six and 12 mo after treatment in five responders （161.9 ± 52.8 pg/mL versus 101.7 ± 47.0 pg/mL and 143.4 ± 46.1 pg/ mL versus 95.4 ± 55.6 pg/mL, respectively）. Hormonal pattern of patients did not significantly change after treatment, with the exception of estradiol levels with an initial reduction and an overall subsequent increment （19.7 ± 6.4 pg/mL versus 13.6 ± 5.0 pg/mL versus 17.3 ± 5.7 pg/mL）. However in 1-year responders a significant increment of free testosterone （14.2 ± 2.54 pg/mL versus 17.1 ± 2.58 pg/mL） occurred. An impairment of nemaspermic morphology occurred, while other seminal parameters did not change significantly during antiviral treatment. CONCLUSION： Patients with HCV infection show worse spermatic parameters than controls, suggesting a possible negative influence of virus on spermatogenesis, with further mild impairment during antiviral treatment. However therapy could improve the spermatic function, as suggested by the increased inhibin B levels and improved hormonal pattern in responders. Further studies are needed to confirm these preliminary intriguing results.

关键词： HCV hepatitis Seminal parameters Antiviral treatment Extrahepatic manifestations

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Can gender predict virological response to standard antiviral therapy for chronic hepatitis C? A retrospective study

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Hepatoma Research 2016年第1期2卷 122-130页

作者： Paola Belci Alessandro Collo Maria Martorana Andrea Evangelista Sara Giunti Roberto Gambino Maurizio Cassader Simona Bo marilena durazzo Department of Medical Sciences University of Turin10126 TurinItaly Department of Economics and Statistics“Cognetti de Martiis” University of Turin10153 TurinItaly

Aim:The liver is a sexually dimorphic organ presenting gender differences in its metabolism,functions,enzyme activity,membrane lipid composition and immune *** paper aimed to assess whether gender may predict virological response to standard antiviral therapy in subjects with chronic hepatitis C(CHC).Methods:The authors retrospectively analyzed 100 patients with genotype 1 CHC(55 men,45 women),who performed standard antiviral therapy(interferon and ribavirin for 12 months)in the period 2002-2012,evaluated with blood tests and abdominal ultrasound to compare different virological and biochemical response in both ***:Rate of substained virological response(SVR)was higher,but not significant,in women than men(46.7%vs.34.5%,P=0.05);difference became significant after stratification by age(<50 and≥50 years).Specifically in the group aged under 50 years,rate of SVR was significantly higher in women than in men(66.7%vs.38.2%,P<0.05).Conclusion:Female gender may predict virological response to standard antiviral therapy in subjects with CHC aged below 50 *** new potent and more expensive antiviral drugs actually available for HCV treatment,it could be useful to identify candidates firstly eligible to therapy.

关键词： Liver gender antiviral therapy

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Determination of Uranium Traces in Nuclear Reactor IEA-R1 Pool Water

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World Journal of Nuclear Science and Technology 2017年第3期7卷 155-166页

作者： Adonis Marcelo Saliba-Silva Olair dos Santos Elita Fontenele Urano de Carvalho Humberto Gracher Riella Michelangelo durazzo Nuclear and Energy Research Institute—IPEN/CNEN-SP S&atilde o Paulo Brazil Chemical Engineering Department Santa Catarina Federal University Florianópolis Brazil

IEA-R1 nuclear reactor operation has the routine to control uranium content in pool water to be in trace range below 50 μg/L. There are several routes to determine the uranium trace content in water in the literature;voltammetry has been systematically employed. In the present study, the chosen chemical determination of uranium traces used the voltammetric method known as AdCSV (adsorptive cathodic stripping voltammetry). This technique, based on mercury voltammetry, is an adequate methodology to determine uranium traces. The chloranilic acid [CAA] (2,5-dichloro-3,6-dihydroxy-1,4-benzo-quinone) is indicated as chelating agent. The redox reaction of UO2+2?with CAA is sensitive in the range of 2 2(CAA)2] reduction potential. In this work, we present the uranium trace results for IEA-R1 reactor water, sampled after an operation routine shutdown. The uranium trace determination for IEA-R1 pool water showed content around 1 μg/L [U] with statistical significance. Therefore the IEA-R1-reactor-water purification showed to be adequate and safe.

关键词： Chloranilic Acid Coolant Water Research Reactor Uranium Voltammetry Uranium Traces

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斑铜矿—黄铜矿体系出溶结构的实验及在天然矿石成因上的应用

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地质科技通报 1983年第1期 95-105页

作者： durazzo A. ,Taylor L.A. ,袁心强

导言本项研究是关于斑铜矿—黄铜矿连晶的出溶结构,因为这种组合在铜矿床中是普遍出现的,而且许多这类的组合被解释为出溶结构(Brett 1964,Ramdohr 1969)。如果把这些自然产出的结构与之在受控制的实验条件形成的结构比较,就能够更好地... 详细信息

导言本项研究是关于斑铜矿—黄铜矿连晶的出溶结构,因为这种组合在铜矿床中是普遍出现的,而且许多这类的组合被解释为出溶结构(Brett 1964,Ramdohr 1969)。如果把这些自然产出的结构与之在受控制的实验条件形成的结构比较,就能够更好地了解它们的成因。Schwatz(1931a)曾经在这方面作过努力。他使用密封的但是没有抽成真空的硼硅酸玻璃试管,用自然产出的斑铜矿—黄铜矿共生组合使之在高于475℃的温度下均一化,再让它

关键词：黄铜矿试料叶片状片状结构硫化矿物板状结构土壤结构斑铜矿铜矿物过饱和度

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Studies on Production Planning of Dispersion Type U₃Si₂-Al Fuel in Plate-Type Fuel Elements for Nuclear Research Reactors

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World Journal of Nuclear Science and Technology 2016年第4期6卷 217-231页

作者： Miguel Luiz Miotto Negro Michelangelo durazzo Marco Aurélio de Mesquita Elita Fontenele Urano de Carvalho Delvonei Alves de Andrade Instituto de Pesquisas Energéticas e Nucleares (Nuclear and Energy Research Institute) S&#227 o Paulo Brazil Escola Politécnica da Universidade de Sã o Paulo (Polytechnic School of Sã o Paulo University) S&#227 o Paulo Brazil

Several fuel plants that supply nuclear research reactors need to increase their production capacity in order to meet the growing demand for this kind of nuclear fuel. After the enlargement of the production capacity of such plants, there will be the need of managing the new production level. That level is usually the industrial one, which poses challenges to the managerial staff. Such challenges come from the fact that several of those plants operate today on a laboratorial basis and do not carry inventory. The change to the industrial production pace asks for new actions regarding planning and control. The production process based on the hydrolysis of UF6 is not a frequent production route for nuclear fuel. Production planning and control of the industrial level of fuel production on that production route is a new field of studies. The approach of the paper consists in the creation of a mathematical linear model for minimization of costs. We also carried out a sensitivity analysis of the model. The results help in minimizing costs in different production schemes and show the need of inventory. The mathematical model is dynamic, so that it issues better results if performed monthly. The management team will therefore have a clearer view of the costs and of the new, necessary production and inventory levels.

关键词： Fabrication of Uranium Silicide Fuel Nuclear Research Reactors Production Planning and Control

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