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| 1 | Nonalcoholic fatty liver disease and vascular disease:State-of-the-art显示文摘Nonalcoholic fatty liver disease(NAFLD), the most common of chronic liver disease in Western Country, is closely related to insulin resistance and oxidative stress and includes a wide spectrum of liver diseases ranging from steatosis alone, usually a benign and non-progressive condition, to nonalcoholic steatohepatitis(NASH), which may progress to liver fibrosis and cirrhosis. NAFLD is considered the hepatic manifestation of the metabolic syndrome with which shares several characteristics, however recent data suggest that NAFLD is linked to increased cardiovascular risk independently of the broad spectrum of risk factors of metabolic syndrome. Accumulating evidence suggests that the clinical burden of NAFLD is not restricted to liver-related morbidity and mortality, with the majority of deaths in NAFLD patients related to cardiovascular disease and cancer and not to the progression of liver disease. Retrospective and prospective studies provide evidence of a strong association between NAFLD and subclinical manifestation of atherosclerosis(increased intima-media thickness, endothelial dysfunction, arterial stiffness, impaired left ventricular function and coronary calcification). A general agreement emerging from these studies indicates that patients with NASH are at higher risk of cardiovascular diseases than those with simple steatosis, emphasizing the role of chronic inflammation in the pathogenesis of atherosclerosis of these patients. It is very likely that the different mechanisms involved in the pathogenesis of atherosclerosis in patients with NAFLD have a different relevance in the patients according to individual genetic background. In conclusion, in the presence of NAFLD patients should undergo a complete cardiovascular evaluation to prevent future atherosclerotic complications. Specific lifestyle modification and aggressive pharmaceutical modification will not only reduce the progression of liver disease, but also reduce morbidity for cardiovascular disease improving overall prognosis and survival. | Silvia Fargion Marianna Porzio Anna Ludovica Fracanzani | 2014 | World Journal of Gastroenterology2014，20，37： | 23 |
| 2 | Diagnostic and therapeutic implications of the association between ferritin level and severity of nonalcoholic fatty liver disease显示文摘Nonalcoholic fatty liver disease(NAFLD),defined by excessive liver fat deposition related to the metabolic syndrome,is a leading cause of progressive liver disease,for which accurate non-invasive staging systems and effective treatments are still lacking.Evidence has shown that increased ferritin levels are associated with the metabolic insulin resistance syndrome,and higher hepatic iron and fat content.Hyperferritinemia and iron stores have been associated with the severity of liver damage in NAFLD,and iron depletion reduced insulin resistance and liver enzymes.Recently,Kowdley et al demonstrated in a multicenter study in 628 adult patients with NAFLD from the NAFLD-clinical research network database with central re-evaluation of liver histology and iron staining that the increased serum ferritin level is an independent predictor of liver damage in patients with NAFLD,and is useful to identify NAFLD patients at risk of non-alcoholic steatohepatitis and advanced fibrosis.These data indicate that incorporation of serum ferritin level may improve the performance of noninvasive scoring of liver damage in patients with NAFLD,and that iron depletion still represents an attractive therapeutic target to prevent the progression of liver damage in these patients. | Luca Valenti Paola Dongiovanni Silvia Fargion | 2012 | World Journal of Gastroenterology2012，18，29： | 15 |
| 3 | 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 |
| 4 | Carotid Artery Intima-media Thickness in Nonalcoholic Fatty Liver Disease显示文摘 | Anna Ludovica Fracanzani Larry Burdick Sara Raselli Paola Pedotti Liliana Grigore Gennaro Santorelli Luca Valenti Alessandra Maraschi Alberico Catapano Silvia Fargion | 2008 | The American Journal of Medicine2008，，1： | 5 |
| 5 | 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 |
| 6 | Cardiovascular risk after orthotopic liver transplantation, a review of the literature and preliminary results of a prospective study显示文摘Improved surgical techniques and greater efficacy of new anti-rejection drugs have significantly improved the survival of patients undergoing orthotopic liver transplantation(OLT). This has led to an increased incidence of metabolic disorders as well as cardiovascular and cerebrovascular diseases as causes of morbidity and mortality in OLT patients. In the last decade, several studies have examined which predisposing factors lead to increased cardiovascular risk(i.e., age, ethnicity, diabetes, NASH, atrial fibrillation, and some echocardiographic parameters) as well as which factors after OLT(i.e., weight gain, metabolic syndrome, immunosuppressive therapy, and renal failure) are linked to increased cardiovascular mortality. However, currently, there are no available data that evaluate the development of atherosclerotic damage after OLT. The awareness of high cardiovascular risk after OLT has not only lead to the definition of new but generally not accepted screening of high risk patients before transplantation, but also to the need for careful patient follow up and treatment to control metabolic and cardiovascular pathologies after transplant. Prospective studies are needed to better define the predisposing factors for recurrence and de novo occurrence of metabolic alterations responsible for cardiovascular damage after OLT. Moreover, such studies will help to identify the timing of disease progression and damage,which in turn may help to prevent morbidity and mortality for cardiovascular diseases. Our preliminary results show early occurrence of atherosclerotic damage, which is already present a few weeks following OLT, suggesting that specific, patient-tailored therapies should be started immediately post OLT. | Giuseppina Pisano Anna L Fracanzani Lucio Caccamo Maria F Donato Silvia Fargion | 2016 | World Journal of Gastroenterology2016，22，40： | 4 |
| 7 | HFE Genotype, Parenchymal Iron Accumulation, and Liver Fibrosis in Patients With Nonalcoholic Fatty Liver Disease显示文摘 | Luca Valenti Anna Ludovica Fracanzani Elisabetta Bugianesi Paola Dongiovanni Enrico Galmozzi Ester Vanni Elena Canavesi Ezio Lattuada Giancarlo Roviaro Giulio Marchesini Silvia Fargion | 2010 | Gastroenterology2010，，3： | 4 |
| 8 | 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 |
| 9 | Practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease显示文摘 | P. Loria L.E. Adinolfi S. Bellentani E. Bugianesi A. Grieco S. Fargion A. Gasbarrini C. Loguercio A. Lonardo G. Marchesini F. Marra M. Persico D. Prati G. Svegliati- Baroni | 2010 | Digestive and Liver Disease2010，，4： | 2 |
| 10 | The SOD2 C47T polymorphism influences NAFLD fibrosis severity: Evidence from case-control and intra-familial allele association studies显示文摘 | Ahmad Al-Serri Quentin M. Anstee Luca Valenti Valerio Nobili Julian B.S. Leathart Paola Dongiovanni Julia Patch Anna Fracanzani Silvia Fargion Christopher P. Day Ann K. Daly | 2011 | Journal of Hepatology2011，，2： | 2 |
| 11 | 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 |
| 12 | Iron in fatty liver and in the metabolic syndrome: A promising therapeutic target显示文摘 | Paola Dongiovanni Anna Ludovica Fracanzani Silvia Fargion Luca Valenti | 2011 | Journal of Hepatology2011，，4： | 2 |
| 13 | Carotid Artery Intima-media Thickness in Nonalcoholic Fatty Liver Disease显示文摘 | Anna Ludovica Fracanzani Larry Burdick Sara Raselli Paola Pedotti Liliana Grigore Gennaro Santorelli Luca Valenti Alessandra Maraschi Alberico Catapano Silvia Fargion | 2008 | The American Journal of Medicine2008，，1： | 2 |
| 14 | Forecasting agriculturally driven global environmental change 显示文摘 | Tilman D Fargione J Wolff B | 2001 | Science2001，，13： | 1 |
| 15 | Hyperferritine, iron o verload, and multiple metabolic alterations identify patients at risk for nonalcoholic steatohepatitis显示文摘 | Fargion S Mattioli M Fracanzani AL | 2001 | Am J Gastroenterol2001，96，8： | 1 |
| 16 | The immunopathogenesis of alcoholic and nonalcoholic steatohepatitis: two triggers for one disease?显示文摘 | Luca Valenti Anna Ludovica Fracanzani Silvia Fargion | 2009 | Seminars in Immunopathology2009，，3： | 1 |
| 17 | Iron in fatty liver and in the metabolic syndrome:a promising therapeutic target显示文摘 | Dongiovanni P Fracanzani AL Fargion S | | 0，，： | 1 |
| 18 | Forecasting agriculturally driven global environmental change显示文摘 | TilmanI D Fargione J Wolff B | 2001 | Science2001，292，： | 1 |
| 19 | A soft computing approach to fuzzy sky-hook control of semiac- tive suspension显示文摘 | CAPONETTO R DIAMANTE O FARGIONE G | 2003 | IEEE Transactions on Control Systems Technoloev2003，11，6： | 1 |
| 20 | Forecasting agriculturally driven global environmental change显示文摘 | TILMAN D FARGIONE J WOLFF B | 2001 | Science2001，292，： | 1 |
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