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| 1 | A randomized trial of iron depletion in patients with nonalcoholic fatty liver disease and hyperferritinemia显示文摘AIM:To compare iron depletion to lifestyle changes alone in patients with severe nonalcoholic fatty liver disease(NAFLD)and hyperferritinemia,a frequent feature associated with more severe liver damage,despite at least 6 mo of lifestyle changes.METHODS:Eligible subjects had to be 18-75 years old who underwent liver biopsy for ultrasonographically detected liver steatosis and hyperferritinemia,ferritin levels≥250 ng/mL,and NAFLD activity score>1.Iron depletion had to be achieved by removing 350 cc of blood every 10-15 d according to baseline hemoglobin values and venesection tolerance,until ferritin<30 ng/mL and/or transferrin saturation(TS)<25%.Thirty-eight patients were randomized 1:1 to phlebotomy(n=21)or lifestyle changes alone(n=17).The main outcome of the study was improvement in liver damage according to the NAFLD activity score at 2 years,secondary outcomes were improvements in liver enzymes[alanine aminotransferases(ALT),aspartate aminotransferase(AST),and gamma-glutamyl-transferases(GGT)].RESULTS:Phlebotomy was associated with normalization of iron parameters without adverse events.In the21 patients compliant to the study protocol,the rate of histological improvement was higher in iron depleted vs control subjects(8/12,67%vs 2/9,22%,P=0.039).There was a better improvement in steatosis grade in iron depleted vs control patients(P=0.02).In patients followed-up at two years(n=35),ALT,AST,and GGT levels were lower in iron-depleted than in control patients(P<0.05).The prevalence of subjects with improvement in histological damage or,in the absence of liver biopsy,ALT decrease≥20%(associated with histological improvement in biopsied patients)was higher in the phlebotomy than in the control arm(P=0.022).The effect of iron depletion on liver damage improvement as assessed by histology or ALT decrease≥20%was independent of baseline AST/ALT ratio and insulin resistance(P=0.0001).CONCLUSION:Iron depletion by phlebotomy is likely associated with a higher rate of improvement of histological liver damage than lifestyle changes alone in patients with NAFLD and hyperferritinemia,and with amelioration of liver enzymes. | Luca Valenti Anna Ludovica Fracanzani Paola Dongiovanni Serena Rovida Raffaela Rametta Erika Fatta Edoardo Alessandro Pulixi Marco Maggioni Silvia Fargion | 2014 | World Journal of Gastroenterology2014，20，11： | 8 |
| 2 | Patatin-like phospholipase domain containing-3 gene I148M polymorphism, steatosis, and liver damage in hereditary hemochromatosis显示文摘AIM: To investigate whether the patatin-like phospholipase domain containing-3 gene (PNPLA3 ) I148M polymorphism is associated with steatosis, fibrosis stage, and cirrhosis in hereditary hemochromatosis (HH). METHODS: We studied 174 consecutive unrelated homozygous for the C282Y HFE mutation of HH (C282Y+/+ HH) patients from Northern Italy, for whom the presence of cirrhosis could be determined based on histological or clinical criteria, without excessive alcohol intake (< 30/20 g/d in males or females) or hepatitis B virus and hepatitis C virus viral hepatitis. Steatosis was evaluated in 123 patients by histology (n = 100) or ultrasound (n = 23). The PNPLA3 rs738409 single nucleotide polymorphism, encoding for the p.148M protein variant, was genotyped by a Taqman assay (assay on demand, Applied Biosystems). The association of the PNPLA3 I148M protein variant (p.I148M) with steatosis, fibrosis stage, and cirrhosis was evaluated by logistic regression analysis. RESULTS: PNPLA3 genotype was not associated with metabolic parameters, including body mass index (BMI), the presence of diabetes, and lipid levels, but the presence of the p.148M variant at risk was independently associated with steatosis [odds ratio (OR) 1.84 per p.148M allele, 95% confidence interval (CI): 1.05-3.31; P = 0.037], independently of BMI and alanine amino-transaminase (ALT) levels. The p.148M variant was also associated with higher aspartate aminotransferase (P = 0.0014) and ALT levels (P = 0.017) at diagnosis, independently of BMI and the severity of iron overload. In patients with liver biopsy, the 148M variant was independently associated with the severity (stage) of fibrosis (estimated coefficient 0.56 ± 0.27, P = 0.041). In the overall series of patients, the p.148M variant was associated with cirrhosis in lean (P = 0.049), but not in overweight patients (P = not significant). At logistic regression analysis, cirrhosis was associated with BMI ≥ 25 (OR 1.82, 95% CI: 1.02-3.55), ferritin > 1000 ng/mL at diagnosis (OR 19.3, 95% CI: 5.3-125), and with the G allele in patients with BMI < 25 (OR 3.26, 95% CI: 1.3-10.3). CONCLUSION: The PNPLA3 I148M polymorphism may represent a permissive factor for fibrosis progression in patients with C282Y+/+ HH. | Luca Valenti Paolo Maggioni Alberto Piperno Raffaela Rametta Sara Pelucchi Raffaella Mariani Paola Dongiovanni Anna Ludovica Fracanzani Silvia Fargion | 2012 | World Journal of Gastroenterology2012，18，22： | 4 |
| 3 | Dietary Iron Overload Induces Visceral Adipose Tissue Insulin Resistance显示文摘 | Paola Dongiovanni Massimiliano Ruscica Raffaela Rametta Stefania Recalcati Liliana Steffani Stefano Gatti Domenico Girelli Gaetano Cairo Paolo Magni Silvia Fargion Luca Valenti | 2013 | The American Journal of Pathology2013，，6： | 3 |
| 4 | Statin use and non-alcoholic steatohepatitis in at risk individuals显示文摘 | Paola Dongiovanni Salvatore Petta Ville Mannisto Rosellina Margherita Mancina Rosaria Pipitone Vesa Karja Marco Maggioni Pirjo Kakela Olov Wiklund Enrico Mozzi Stefania Grimaudo Dorota Kaminska Raffaela Rametta Antonio Craxi Silvia Fargion Valerio Nobili | 2015 | Journal of Hepatology2015，，3： | 2 |
| 5 | Increased expression and activity of the transcription factor FOXO1 in nonalcoholic steatohepatitis显示文摘 | Valenti L Rametta R Dongiovanni P | | 0，，： | 1 |
| 6 | Increased expression and activity of the transcription factor FOXO1 in nonalcoholic steatohepatitis显示文摘 | Valenti L Rametta R Dongiovanni P | | 0，，： | 1 |
| 7 | Hepatic Notch Signaling Correlates with Insulin Resistance and Non-Al- coholic Fatty Liver Disease显示文摘 | VALENTI L MENDOZA RM RAMETTA R | 2013 | Diabetes2013，，： | 1 |
| 8 | DJ-1 modulates alphasynuclein aggregation state in a cellular model of oxidative stress:relevance for Parkinson’s disease and involvement of HSP70显示文摘 | Batelli S Albani D Rametta R | 2008 | PLo S One2008，3，4： | 1 |
| 9 | Genetic variants regulating insulin receptor signalling are associated with the severity of liver damage in patients with non-alcoholic fatty liver disease显示文摘 | Dongiovanni P Valenti L Rametta R | 2010 | Gut2010，59，2： | 1 |
| 10 | The APOC3 T-455C and C-482T promoter region polymorphisms are not associated with the severity of liver damage independently of PNPLA3 I148M genotype in patients with nonalcoholic fatty liver显示文摘 | Luca Valenti Valerio Nobili Ahmad Al-Serri Raffaela Rametta Julian B.S. Leathart Marco A. Zappa Paola Dongiovanni Anna L. Fracanzani Arianna Alterio Giancarlo Roviaro Ann K. Daly Silvia Fargion Christopher P. Day | 2011 | Journal of Hepatology2011，，6： | 1 |
| 11 | Toxic effects of ZnO nanoparticles towards marine algae Dunaliella tertiolecta显示文摘 | Sonia Manzo Maria Lucia Miglietta Gabriella Rametta Silvia Buono Girolamo Di Francia | 2012 | Science of the Total Environment2012，，： | 1 |
| 12 | Liver transplantation for hepatocellular carcinoma in a patient with a novel telomerase mutation and steatosis显示文摘 | Luca Valenti Paola Dongiovanni Marco Maggioni Benedetta Maria Motta Raffaela Rametta Marta Milano Silvia Fargion Paolo Reggiani Anna Ludovica Fracanzani | 2012 | Journal of Hepatology2012，，： | 1 |
| 13 | Increased expression and activity of the transcription factor FOXOI in nonalcoholic steatohepatitis显示文摘 | Valenti L Rametta R Dongiovanni P | 2008 | Diabetes2008，57，5： | 1 |
| 14 | Toxic effects of ZnO nanoparticles towards marine algae Dunaliella tertiolecta显示文摘 | Manzo S Miglietta M L Rametta G | 2013 | Science of the Total Environment2013，，： | 1 |
| 15 | DJ-1 modulates alpha-synuclein aggregation state in a cellular model of oxidative stress:relevance for Parkinson\'s disease and involvement of HSP70 显示文摘 | Batelli S Albani D Rametta R Polito L Prato F Pesaresi M | 2008 | PLoS One2008，3，： | 1 |
| 16 | Effect of the A736V TMPRSS6 polymorphism on the penetrance and clinical expression of hereditary hemochromatosis显示文摘 | Luca Valenti Anna Ludovica Fracanzani Raffaela Rametta Mirella Fraquelli Giulia Soverini Serena Pelusi Paola Dongiovanni Dario Conte Silvia Fargion | 2012 | Journal of Hepatology2012，，6： | 1 |
| 17 | Transmembrane 6 superfamily member 2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease显示文摘 | Paola Dongiovanni Salvatore Petta Cristina Maglio Anna Ludovica Fracanzani Rosaria Pipitone Enrico Mozzi Benedetta Maria Motta Dorota Kaminska Raffaela Rametta Stefania Grimaudo Serena Pelusi Tiziana Montalcini Anna Alisi Marco Maggioni Vesa K?rj? Jan Bor | 2015 | Hepatology2015，，2： | 1 |
| 18 | Hepatic steatosis and PNPLA3 I148M variant are associated with serum fetnin-A inde- pendently of insulin resistance 显示文摘 | Rametta R Ruseica M Dongiovanni P | 2014 | Enr J Clin Invest2014，44，7： | 1 |
| 19 | MERTK rs4374383 polymorphism affects the severity of fibrosis in nonalcoholic fatty liver disease显示文摘 | Salvatore Petta Luca Valenti Fabio Marra Stefania Grimaudo Claudio Tripodo Elisabetta Bugianesi Calogero Cammà Andrea Cappon Vito Di Marco Giovanni Di Maira Paola Dongiovanni Raffaela Rametta Alessandro Gulino Enrico Mozzi Emanuele Orlando Marco Maggioni | 2015 | Journal of Hepatology2015，，： | 1 |
| 20 | DJ-1modulates alpha-synuclein aggregation state in a cellular model of oxidative stress:relevance for Parkinson’s dis-ease and involvement of HSP70显示文摘 | Batelli S Albani D Rametta R Polito L Prato F Pesaresi M etal | 2008 | PLoS One2008，3，： | 1 |
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