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| 1 | Downstaging disease in patients with hepatocellular carcinoma outside up-to-seven criteria: Strategies using degradable starch microspheres transcatheter arterial chemo-embolization显示文摘AIM: To evaluate the downstaging rates in hepatitis C virus-patients with hepatocellular carcinoma(HCC), treated with degradable starch microspheres transcatheter arterial chemoembolization(DSM-TACE), to reach new-Milan-criteria(nM C) for transplantation. METHODS: This study was approved by the Ethics Committee of our institution. From September 2013 to March 2014 eight patients(5 men and 3 women) with liver cirrhosis and multinodular HCC, that did not meet n MC at baseline, were enrolled in this study. Patients who received any other type of treatment such as termal ablation or percutaneous ethanol injection were excluded. DSM-TACE was performed in all patients using Embo Cept? S and doxorubicin. Baseline and follow-up computed tomography or magnetic resonance imaging was assessed measuring the longest enhancing axial dimension of each tumor according to the modified Response Evaluation Criteria In Solid Tumors measure-ments, and medical records were reviewed.RESULTS: DSM-TACE was successfully performed in all patients without major complication. We treated 35 lesions(mean 4.3 per patient). Six of eight patients(75%) had their HCC downstaged to meet nM C. Every patient whose disease was downstaged eventually underwent transplantation. The six patients who received transplant were still living at the time of this writing, without recurrence of HCC. Baseline age(P = 0.25), Model for End-stage Liver Disease score(P = 0. 77), and α-fetoprotein level(P = 1.00) were similar between patients with and without downstaged HCC. CONCLUSION: DSM-TACE represents a safely and effective treatment option with similar safety and efficacy of conventional chemoembolization and could be successfully performed also for downstaging disease in patients without n MC, allowing them to reach liver transplantation. | Antonio Orlacchio Fabrizio Chegai Stefano Merolla Simona Francioso Costantino Del Giudice Mario Angelico Giuseppe Tisone Giovanni Simonetti | 2015 | World Journal of Hepatology2015，7，12： | 23 |
| 2 | Understanding the pathophysiological mechanisms in the pediatric non-alcoholic fatty liver disease: The role of genetics显示文摘Classically, the non-alcoholic fatty liver disease(NAFLD) physiopathology and progression has been summarized in the two hits hypothesis. The first hit is represented by the action of hyperinsulinemia and insulin resistance, accompanying obesity, that leads to liver steatosis increasing the absolute non esterified fatty acids uptake in the liver and the esterification to form triacylglycerol. The oxidative stress is involved in the second hit leading to the progression to nonalcoholic steatohepatitis(NASH) because of its harmful action on steatosic hepatocytes. However, at the present time, the two hits hypothesis needs to be updated because of the discover of genetic polymorphisms involved both in the liver fat accumulation and progression to NASH that make more intriguing understanding the NAFLD pathophysiological mechanisms. In this editorial, we want to underline the role of PNPLA3 I148 M, GPR120 R270 H and TM6SF2 E167 K in the pediatric NAFLD development because they add new pieces to the comprehension of the NAFLD pathophysiological puzzle. The PNPLA3 I148 M polymorphism encodes for an abnormal protein which predisposes to intrahepatic triglycerides accumulation both for a loss-of-function of its triglyceride hydrolase activity and for a gain-of-function of its lipogenic activity.Therefore, it is involved in the first hit, such as TM6SF2 E167 K polymorphisms that lead to intrahepatic fat accumulation through a reduced very low density lipoprotein secretion. On the other hand, the GPR120 R270 H variant, reducing the anti-inflammatory action of the GPR120 receptor expressed by Kuppfer cells, is involved in the second hit leading to the liver injury. | Pierluigi Marzuillo Anna Grandone Laura Perrone Emanuele Miraglia del Giudice | 2015 | World Journal of Hepatology2015，7，11： | 9 |
| 3 | Clinical significance of NOD2/CARD15 and Toll-like receptor 4 gene single nucleotide polymorphisms in inflammatory bowel disease显示文摘AIM: To evaluate the role of genetic factors in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC), we investigated the single nucleotide poly- morphisms (SNPs) of NOD2/CARD15 (R702W, G908R and L1007fi nsC), and Toll-like receptor 4 (TLR4) genes (D299G and T399I) in a selected inflammatory bowel disease (IBD) population coming from Southern Italy. METHODS: Allele and genotype frequencies of NOD2/ CARD15 (R702W, G908R and L1007finsC) and TLR4 (D299G and T399I) SNPs were examined in 133 CD pa-tients, in 45 UC patients, and in 103 healthy controls. A genotype-phenotype correlation was performed. RESULTS: NOD2/CARD15 R702W mutation was sig-nificantly more frequent in CD (9.8%) than in controls (2.4%, P = 0.001) and in UC (2.3%, P = 0.03). No sig-nificant difference was found between UC patients and control group (P > 0.05). In CD and UC patients, no signifi cant association with G908R variant was found. L1007f insC SNP showed an association with CD (9.8%) compared with controls (2.9%, P = 0.002) and UC patients (2.3%, P = 0.01). Moreover, in CD patients, G908R and L1007finsC mutations were significantly associated with different phenotypes compared to CD wild-type patients. No association of IBD with the TLR4 SNPs was found in either cohort (allele frequencies: D299G-controls 3.9%, CD 3.7%, UC 3.4%, P > 0.05; T399I-controls 2.9%, CD 3.0%, UC 3.4%, P > 0.05). CONCLUSION: These findings confirm that, in our IBD patients selected from Southern Italy, the NOD2/ CARD15, but not TLR4 SNPs, are associated with in-creased risk of CD. | Luciana Rigoli Claudio Romano Rosario Alberto Caruso Maria A Lo Presti Chiara Di Bella Vincenzo Procopio Giuseppina Lo Giudice Maria Amorini Giuseppe Costantino Maria D Sergi Caterina Cuppari Giovanna Elisa Calabrò Romina Gallizzi Carmelo Damiano Salpietro Walter Fries | 2008 | World Journal of Gastroenterology2008，14，28： | 8 |
| 4 | Red wine and green tea reduce H pylori- or VacA-induced gastritis in a mouse model显示文摘AIM: To investigate whether red wine and green tea could exert anti-H pylori or anti-VacA activity in vivo in a mouse model of experimental infection.METHODS: Ethanol-free red wine and green tea concentrates were administered orally as a mixture of the two beverages to H pylori infected mice, or separately to VacA-treated mice. Gastric colonization and gastric in? ammation were quantifi ed by microbiological, histopathological, and immunohistochemical analyses. RESULTS: In H pylori -infected mice, the red wine and green tea mixture significantly prevented gastritis and limited the localization of bacteria and VacA to the surface of the gastric epithelium. Similarly, both beverages significantly prevented gastric epithelium damage in VacA-treated mice; green tea, but not red wine, also altered the VacA localization in the gastric epithelium. CONCLUSION: Red wine and green tea are able to prevent H pylori -induced gastric epithelium damage, possibly involving VacA inhibition. This observation supports the possible relevance of diet on the pathological outcome of H pylori infection. | Paolo Ruggiero Giacomo Rossi Francesco Tombola Laura Pancotto Laura Lauretti Giuseppe Del Giudice Mario Zoratti | 2007 | World Journal of Gastroenterology2007，13，3： | 6 |
| 5 | From the liver to the heart: Cardiac dysfunction in obese children with non-alcoholic fatty liver disease显示文摘In the last decades the prevalence of non-alcoholic fatty liver disease(NAFLD) has increased as a consequence of the childhood obesity world epidemic. The liver damage occurring in NAFLD ranges from simple steatosis to steatohepatitis, fibrosis and cirrhosis. Recent findings reported that fatty liver disease is related to early atherosclerosis and cardiac dysfunction even in the pediatric population. Moreover, some authors have shown an association between liver steatosis and cardiac abnormalities, including rise in left ventricular mass, systolic and diastolic dysfunction and epicardial adipose tissue thickness. In this editorial, we provide a brief overview of the current knowledge concerning the association between NAFLD and cardiac dysfunction. | Anna Di Sessa Giuseppina Rosaria Umano Emanuele Miraglia del Giudice Nicola Santoro | 2017 | World Journal of Hepatology2017，9，2： | 5 |
| 6 | A systematic review and meta-analysis of clinical trials implementing aromatase inhibitors to treat male infertility显示文摘Aromatase activity has commonly been associated with male infertility characterized by testicular dysfunction with low serum testosterone and/or testosterone to estradiol ratio.In this subset of patients,and particularly in those with hypogonadism,elevated levels of circulating estradiol may establish a negative feedback on the hypothalamic–pituitary–testicular axis by suppressing follicle-stimulating hormone(FSH)and luteinizing hormone(LH)production and impaired spermatogenesis.Hormonal manipulation via different agents such as selective estrogen modulators or aromatase inhibitors to increase endogenous testosterone production and improve spermatogenesis in the setting of infertility is an off-label option for treatment.We carried out a systematic review and meta-analysis of the literature of the past 30 years in order to evaluate the benefits of the use of aromatase inhibitors in the medical management of infertile/hypoandrogenic males.Overall,eight original articles were included and critically evaluated.Either steroidal(Testolactone)or nonsteroidal(Anastrozole and Letrozole)aromatase inhibitors were found to statistically improve all the evaluated hormonal and seminal outcomes with a safe tolerability profile.While the evidence is promising,future prospective randomized placebo-controlled multicenter trials are necessary to better define the efficacy of these medications. | Francesco Del Giudice Gian Maria Busetto Ettore De Berardinis Isabella Sperduti Matteo Ferro Martina Maggi Martin S Gross Alessandro Sciarra Michael L Eisenberg | 2020 | Asian Journal of Andrology2020，22，4： | 5 |
| 7 | Pediatric non-alcoholic fatty liver disease:New insights and future directions显示文摘One of the most common complications of childhood obesity is the non-alcoholic fatty liver disease(NAFLD),which is the most common form of liver disease in children.NAFLD is defined by hepatic fat infiltration > 5% hepatocytes,as assessed by liver biopsy,in the absence of excessive alcohol intake,viral,autoimmune and drug-induced liver disease.It encompasses a wide spectrum of liver diseases ranging from simple steatosis to non-alcoholic steatohepatitis,which,in turn,can evolve into cirrhosis and end stage liver disease.Obesity and insulin resistance are the main risk factors for pediatric NAFLD.In fact,NAFLD is strongly associated with the clinical features of insulin resistance especially the metabolic syndrome,prediabetes and type 2 diabetes mellitus(T2D).In particular,it has been clearly shown in obese youth that the prevalence of metabolic syndrome,pre-diabetes and type 2 diabetes increaseswith NAFLD severity progression.Evidence that not all of the obese patients develop NAFLD suggests that the disease progression is likely to depend on complex interplay between environmental factors and genetic predisposition.Recently,a non-synonymous SNP(rs738409),characterized by a C to G substitution encoding an isoleucine to methionine substitution at the amino acid position 148 in the patatin like phospholipase containing domain 3 gene(PNPLA3),has been associated with hepatic steatosis in a multiethnic cohort of adults as well as in children.Another important polymorphisms that acts with PNPLA3 to convey susceptibility to fatty liver in obese youths is the rs1260326 polymorphism in the glucokinase regulatory protein.The pharmacological approach in NAFLD children poorly adherent to or being unresponsive/partially responsive to lifestyle changes,is aimed at acting upon specific targets involved in the pathogenesis.There are some therapeutic approaches that are being studied in children.This article reviews the current knowledge regarding the pediatric fatty liver disease,the new insights and the future directions. | Pierluigi Marzuillo Emanuele Miraglia del Giudice Nicola Santoro | 2014 | World Journal of Hepatology2014，6，4： | 4 |
| 8 | TM6SF2 E167K variant predicts severe liver fibrosis for human immunodeficiency/hepatitis C virus co-infected patients, and severe steatosis only for a non-3 hepatitis C virus genotype显示文摘AIM To evaluate the impact of the Glu167Lys(E167K) transmembrane 6 superfamily member 2(TM6SF2) variant on the biochemical and morphologic expression of liver lesions in human immunodeficiency virus(HIV)/hepatitis C virus(HCV) co-infected patients.METHODS The study comprised 167 consecutive patients with HIV/HCV coinfection and biopsy-proven chronic hepatitis. A pathologist graded liver fibrosis and necroinflammation using the Ishak scoring system, and steatosis using Kleiner's scoring system. Patients were genotyped for TM6SF2 E167K(rs58542926) by real-time Polymerase chain reaction. The 167 patients, 35 therapy-naive and 132 receiving ART, were prevalently males(73.6%), the median age was 40.7 years and the immunological condition good(median CD4+ cells/mm3 = 505.5).RESULTS The 17 patients with the TM6SF2 E167 K variant, compared with the 150 with TM6SF2-E/E, showed higher AST(P = 0.02) and alanine aminotransferase(P = 0.02) and higher fibrosis score(3.1 ± 2.0 vs 2.3 ± 1.5, P = 0.05). In a multivariate analysis, TM6SF2 E167 K was independently associated with severe fibrosis. The same analysis showed that HCV-genotype 3, present in 42.2% of patients was an independent predictor of severe steatosis. The association of TM6SF2 E167 K with severe steatosis, absent for the whole group of 167 patients, was re-evaluated separately for HCVgenotype 3 and non-3 patients: No factor was independently associated with severe steatosis in the HCV-genotype-3 subgroup, whereas an independent association was observed between severe steatosis and TM6SF2 E167 K in non-3 HCV genotypes. No association between the TM6SF2 E167 K variant and severe liver necroinflammation was observed.CONCLUSION In HIV/HCV coinfection the TM6SF2 E167 K variant is an independent predictor of severe fibrosis, but appears to be independently associated with severe steatosis only for patients with a non-3 HCV genotype. | Caterina Sagnelli Marco Merli Caterina Uberti-Foppa Hamid Hasson Anna Grandone Grazia Cirillo Stefania Salpietro Carmine Minichini Mario Starace Emanuela Messina Patrizia Morelli Emanuele Miraglia Del Giudice Adriano Lazzarin Nicola Coppola Evangelista Sagnelli | 2016 | World Journal of Gastroenterology2016，22，38： | 4 |
| 9 | Abdominal fat interacts with PNPLA 3 I148M, but not with the APOC 3 variant in the pathogenesis of liver steatosis in chronic hepatitis C显示文摘 | R. Zampino N. Coppola G. Cirillo A. Boemio M. Pisaturo A. Marrone M. Macera E. Sagnelli L. Perrone L. E. Adinolfi E. Miraglia del Giudice | 2013 | J Viral Hepat2013，，8： | 3 |
| 10 | TM 6 SF 2 E167K variant is associated with severe steatosis in chronic hepatitis C, regardless of PNPLA 3 polymorphism显示文摘 | Nicola Coppola Zampino Rosa Grazia Cirillo Maria Stanzione Margherita Macera Adriana Boemio Anna Grandone Mariantonietta Pisaturo Aldo Marrone Luigi E. Adinolfi Evangelista Sagnelli Emanuele Miraglia del Giudice | 2015 | Liver Int2015，，8： | 3 |
| 11 | Abdominal fat interacts with PNPLA 3 I148M, but not with the APOC 3 variant in the pathogenesis of liver steatosis in chronic hepatitis C显示文摘 | R. Zampino N. Coppola G. Cirillo A. Boemio M. Pisaturo A. Marrone M. Macera E. Sagnelli L. Perrone L. E. Adinolfi E. Miraglia del Giudice | 2013 | J Viral Hepat2013，，8： | 3 |
| 12 | Pediatric fatty liver disease:Role of ethnicity and genetics显示文摘Non-alcoholic fatty liver disease(NAFLD)comprehends a wide range of conditions,encompassing from fatty liver or steatohepatitis with or without fibrosis,to cirrhosis and its complications.NAFLD has become the most common form of liver disease in childhood as its prevalence has more than doubled over the past 20years,paralleling the increased prevalence of childhood obesity.It currently affects between 3%and11%of the pediatric population reaching the rate of46%among overweight and obese children and adolescents.The prevalence of hepatic steatosis varies among different ethnic groups.The ethnic group with the highest prevalence is the Hispanic one followed by the Caucasian and the African-American.This evidence suggests that there is a strong genetic background in the predisposition to fatty liver.In fact,since 2008several common gene variants have been implicated in the pathogenesis of fatty liver disease.The most important is probably the patatin like phospholipase containing domain 3 gene(PNPLA3)discovered by the Hobbs’group in 2008.This article reviews the current knowledge regarding the role of ethnicity and genetics in pathogenesis of pediatric fatty liver. | Pierluigi Marzuillo Emanuele Miraglia del Giudice Nicola Santoro | 2014 | World Journal of Gastroenterology2014，20，23： | 3 |
| 13 | Electromagnetic field and spontaneous symmetry breaking in biological matter 显示文摘 | Giudice E Del Doglia S Milani M | 1986 | Nucl Phys B1986，275，： | 2 |
| 14 | Association Between a Polymorphism in Cannabinoid Receptor 2 and Severe Necroinflammation in Patients With Chronic Hepatitis C显示文摘 | Nicola Coppola Rosa Zampino Giulia Bellini Margherita Macera Aldo Marrone Mariantonietta Pisaturo Adriana Boemio Bruno Nobili Giuseppe Pasquale Sabatino Maione Luigi Elio Adinolfi Laura Perrone Evangelista Sagnelli Emanuele Miraglia Del Giudice Francesca | 2013 | Clinical Gastroenterology and Hepatology2013，，： | 2 |
| 15 | Endometriosis显示文摘 | Linda C Giudice Lee C Kao | 2004 | 2004 (9447)2004，，9447： | 2 |
| 16 | Insulin resistance and steatosis in HBV-HCV co-infected patients: Role of PNPLA3 polymorphisms and impact on liver fibrosis progression显示文摘AIM:To evaluate steatosis,insulin resistance(IR)and patatin-like phospholipase domain-containing 3(PNPLA3) and their relation to disease progression in hepatitis B and C viruses(HCV-HBV) coinfected patients.METHODS:Three hundred and thirty patients with biopsy proven chronic hepatitis were enrolled:66 had HBV-HCV,66 HBV and 198 HCV infection.Prevalence of steatosis,IR and PNPLA3 polymorphisms and their relation to anthropometric,biochemical,virological and histological parameters were evaluated.RESULTS:Prevalence of steatosis in group HBV-HCV was similar to that in HCV(47.0% vs 49.5%,respec-tively);group HBV showed the lowest steatosis(33.3%).Group HBV-HCV had a lesser degree of steatosis than HCV(P = 0.016),lower HCV RNA levels(P = 0.025) and lower prevalence and degree of IR(P = 0.01).PNPLA3 polymorphisms were associated with steatosis.Group HBV-HCV showed higher levels of liver fibrosis than group HCV(P = 0.001),but similar to that ob-served in HBV group.In HBV-HCV group,liver fibrosis was not associated with steatosis,IR or PNPLA3.HBV infection was the independent predictor of advanced liver fibrosis.CONCLUSION:HBV-HCV co-infected patients have lower degree of hepatic steatosis,IR and HCV RNA than HCV mono-infected;co-infected patients showed a more rapid liver fibrosis progression that seems to be due to the double infection and/or HBV dominance. | Rosa Zampino Adriana Boemio Aldo Marrone Luciano Restivo Maria Chiara Fascione Riccardo Nevola Luigi Elio Adinolfi Nicola Coppola Carmine Minichini Mario Starace Evangelista Sagnelli Grazia Cirillo Emanuele Miraglia del Giudice Maria Stanzione Emanuele Durante-Mangoni Giovanna Salzillo | 2014 | World Journal of Hepatology2014，6，9： | 2 |
| 17 | Rituximab-induced IgG hypogammaglobulinemia in children with nephrotic syndrome and normal pre-treatment IgG values显示文摘BACKGROUND In paediatric patients with complicated nephrotic syndrome(NS), rituximab(RTX) administration can induce persistent IgG hypogammaglobulinemia among subjects showing low basal immunoglobulin G(IgG) levels.AIM To evaluate the effect of RTX on IgG levels and infections in patients with complicated NS and normal basal IgG levels.METHODS We consecutively enrolled all patients with complicated NS and normal basal IgG levels undergoing the first RTX infusion from January 2008 to January 2016. Basal IgG levels were dosed after 6 wk of absent proteinuria and with a maximal interval of 3 mo before RTX infusion. The primary outcome was the onset of IgG hypogammaglobulinemia during the follow-up according to the IgG normal values for age [mean ± standard deviation(SD)].RESULTS We enrolled 20 patients with mean age at NS diagnosis of 4.2 ± 3.3 years. The mean age at the first RTX infusion was 10.9 ± 3.5 years. Eleven out of twenty patients(55%) developed IgG hypogammaglobulinemia. None of these patients showed severe or recurrent infections. Only one patient suffered from recurrent acute otitis media and underwent substitutive IgG infusion. Three patients undergoing only the two 'starting doses' experienced normalization of IgG levels. Using Kaplan-Meier analysis, the cumulative proportion of patients free of IgG hypogammaglobulinemia was 57.8% after the first RTX dose, 51.5% after the third dose, 44.1% after the fourth dose, and 35.5% after the fifth dose.CONCLUSION RTX can induce IgG hypogammaglobulinemia in patients with pre-RTX IgG normal values. None of the treated patients showed severe infections. | Pierluigi Marzuillo Stefano Guarino Tiziana Esposito Anna Di Sessa Sara Immacolata Orsini Daniela Capalbo Emanuele Miraglia del Giudice Angela La Manna | 2019 | World Journal of Clinical Cases2019，7，9： | 2 |
| 18 | Towards the development of vaccines against Helicobacter pylori:status and issues 显示文摘 | | 2001 | Curr Opin Investig Drugs2001，2，： | 1 |
| 19 | Endocrine-disrupting chemicals: an Endocrine Society scientific statement显示文摘 | Diamanti-Kandarakis E Bourguignon JP Giudice LC | 2009 | Endocr Rev2009，30，4： | 1 |
| 20 | Endometriosis显示文摘 | Giudice L C Clinical practice | | 0，，25： | 1 |
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