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World Journal of Gastroenterology 2012年第29期18卷 3782-3786页

作者： Luca Valenti Paola Dongiovanni silvia fargion Università degli Studi di Milano Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico20122 MilanoItaly

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 *** has shown that increased ferritin levels are associated with the metabolic insulin resistance syndrome,and higher hepatic iron and fat *** and iron stores have been associated with the severity of liver damage in NAFLD,and iron depletion reduced insulin resistance and liver ***,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 *** 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.

关键词： Fibrosis Ferritin Iron overload Nonalcoholic fatty liver disease Steatohepatitis Steatosis

Triple antiviral therapy in HCV positive patients who failed prior combination therapy

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World Journal of Gastroenterology 2006年第33期12卷 5293-5300页

作者： silvia fargion Mauro Borzio Alessandra Maraschi Antonietta Cargnel Internal Medicine Ospedale Maggiore Policlinico Mangiagalli e Regina Elena Fondazione IRCCS University of Milan Milan Italy Internal Medicine Gastroenterology Unit Fatebenefratelli Hospital Milan Italy II Department of Infectious Diseases L. Sacco Hospital Milan Italy

AIM： To assess the efficacy of triple therapy （peginterferon or high dose standard interferon, plus ribavirin and amantadine） in nonresponders to prior combination therapy. METHODS： A total of 196 patients were enrolled in a multicenter, open, randomized study. Patients were given 180 μg/wk of peginterferon-alpha-2a （40 kD） plus ribavirin （800-1000 rag/d） and amantadine （200 rag/d） for 48 wk （group A） or interferon-alpha-2a （6 MU/d for 4 wk, 3 MU/d for 20 wk, and 3 MU tiw for 24 wk） plus ribavirin （800-1000 rag/d） and amantadine （200 rag/d） for 48 wk （group B）. RESULTS： Overall sustained virologic response （SVR） was 26.6% （32.1% and 19.5% in group A and B, P = 0.057）. Baseline ALT 〉120 UI/L （OR 2.4; 95% CI：1.11 to 5.20; P = 0.026） and HCV RNA negativity after 12 wk （OR 8.7; 95% CI： 3.87 to 19.74; P 〈 0.0001） were independently associated with SVR. Therapy discontinuation occurred less frequently in patients treated with peginterferon than standard interferon （P = 0.036）. CONCLUSION： More than 25% of nonresponders to combination therapy can eradicate HCV infection when retreated with triple therapy, especially if they have a high baseline ALT and are treated with pegylated interferon.

关键词： Hepatitis C Nonresponders Peginterferon Ribavirin Amantadine

Nonalcoholic fatty liver disease and vascular disease:State-of-the-art

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World Journal of Gastroenterology 2014年第37期20卷 13306-13324页

作者： silvia fargion Marianna Porzio Anna Ludovica Fracanzani Department of Pathophysiology and Transplantation Metabolic Liver Diseases Research CenterCa’ Granda IRCCS FoundationPoliclinico Hospital Pad Granelli

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 diseas

关键词： Intima-media thickness Steatosis Nonalcoholic fatty liver disease Non-alcoholic steatohepatitis Early atherosclerosis Cardiovascular risk Inflammation Epicardic fat

Cardiovascular risk after orthotopic liver transplantation, a review of the literature and preliminary results of a prospective study

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World Journal of Gastroenterology 2016年第40期22卷 8869-8882页

作者： Giuseppina Pisano Anna L Fracanzani Lucio Caccamo Maria F Donato silvia fargion Unit of Internal Medicine Department of Pathophysiology and Transplantation Ca’ Granda IRCCS Foundation Policlinico Hospital University of Milan Unit of Hepatic Surgery Department of Pathophysiology and Transplantation Ca’ Granda IRCCS Foundation Policlinico Hospital University of Milan Division of Gastroenterology Department of Pathophysiology and Transplantation Ca’ Granda IRCCS Foundation Policlinico Hospital University of Milan

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.

关键词： Orthotopic liver transplant Cardiovascular risk Atherosclerosis Non-alcoholic fatty liver disease Intima-media thickness Epicardial fat thickness Diastolic dysfunction

Patatin-like phospholipase domain containing-3 gene I148M polymorphism, steatosis, and liver damage in hereditary hemochromatosis

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World Journal of Gastroenterology 2012年第22期18卷 2813-2820页

作者： Luca Valenti Paolo Maggioni Alberto Piperno Raffaela Rametta Sara Pelucchi Raffaella Mariani Paola Dongiovanni Anna Ludovica Fracanzani silvia fargion Università degli Studi di Milano Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico 20122 Milano Italy Università di Milano Bicocca Ospedale San Gerardo Monza 20090 Monza MI Italy

AIM： To investigate whether the patatin-/ike phosph- olipase 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 ul- trasound （n = 23）. The PNPLA3 rs738409 single nucle- otide 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 pres- ence 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）, ferri

关键词： Fatty liver Fibrosis Hemochromatosis HFEprotein Iron overload Patatin-like phospholipase domaincontaining-3 gene Steatosis

A novel alpha1-antitrypsin null variant (PiQ0_(Milano))

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World Journal of Hepatology 2013年第8期5卷 458-461页

作者： Raffaela Rametta Gabriella Nebbia Paola Dongiovanni Marcello Farallo silvia fargion Luca Valenti Department of Pathophysiology and Transplantation Università degli Studi di Milano Internal Medicine Fondazione IRCCS Ca’ Granda Ospedale Policlinico Milano Pediatric Clinic Fondazione IRCCS Ca’ Granda Ospedale Policlinico

Alpha1-antitrypsin deficiency is an autosomal recessive disease characterized by reduced serum levels of alpha1-antitrypsin(AAT)due to mutations in the SERPINA1 gene causing early onset pulmonary emphysema and,occasionally,chronic liver *** report an incidental finding of a novel null AAT allele,Q0Milano,consisting of a 17 nucleotides deletion in exon 3 of SERPINA1 gene,in an Italian child with persistently increased liver enzymes,a mild decrease in circulating AAT levels and without any pulmonary disease.Q0Milano variant results in an unfunctional protein lacking of AAT active site,as the resultant protein is truncated near PiS locus involved in AAT protein stability.

关键词： Alpha1-antitrypsin deficiency Rare variant Alpha1-antitrypsin null mutation Liver disease

A randomized trial of iron depletion in patients with nonalcoholic fatty liver disease and hyperferritinemia

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World Journal of Gastroenterology 2014年第11期20卷 3002-3010页

作者： Luca Valenti Anna Ludovica Fracanzani Paola Dongiovanni Serena Rovida Raffaela Rametta Erika Fatta Edoardo Alessandro Pulixi Marco Maggioni silvia fargion Department of Pathophysiology and Transplantation Metabolic Liver Diseases Research CenterUniversità degli Studi di MilanoFondazione IRCCS Ca' Granda Ospedale Policlinicovia F Sforza 3520122MilanoItaly

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... 详细信息

关键词： Nonalcoholic fatty liver disease Iron depletion Randomized controlled trial Ferritin

Staphylococcus haemolyticus superinfection of legionella pneumonia during infliximab therapy

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Open Journal of Internal Medicine 2011年第1期1卷 6-8页

作者： Marianna Porzio Luca Valenti Daniela Bignamini Francesca Ricchini Alessandro Palleschi Paolo Tarsia silvia fargion 不详

We present the case of a 42-year-old man affected by psoriasis with Staphylococcus Haemolyticus superin-fection of Legionella pneumonia during infliximab therapy. The introduction of compounds that block TNF-α has yielded great benefits for patients affected by selected autoimmune diseases that fail to respond to classic anti-inflammatory agents, but, on the other hand, has led to an increased susceptibility to infec-tions, in particular of those caused by intracellular pathogens, such as L. Pneumophila. Emerging evi-dence suggests that legionellosis can be complicated by superinfection with other agents, including sap-rophytic microorganisms, among which coagulase- negative staphylococci. To our knowledge, this is the first report of systemic legionellosis with superinfec-tion by S. Haemolyticus, an emerging nosocomial multi-resistant pathogen that commonly causes sep-ticemia, osteomyelitis or endocarditis, but has not so far been associated with necrotizing pneumonia. De-spite the optimal antimicrobial therapy for Staphylo-coccus spp. pneumonia is still controversial, evidence suggests that in patients with confirmed positivity for methicillin resistant strains, particularly if sensitivity to vancomycin is suboptimal, linezolid should be the first choice therapy, being superior to vancomycin and teicoplanin.

关键词： Infliximab Legionella Pneumophila Linezolid Necrotizing Pneumonia Psoriasis Staphylococcus Haemolyticus

对比增强超声用于肝脏局灶性病变定性诊断与对比增强CT比较的药物经济学评估报告

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中国药物经济学 2008年第2期3卷 35-38页

作者： Prof.silvia fargion Prof.Mario Mondelli Ospedale Maggiore Di Milano via Francesco Sforza 28-20122 Milano Policlinico San Matteo Istituto Di Ricovero E Cura A Carattere Scientifico-Di Diritto Publico 27100 Pavia-V.le Golgi 19

本文采用最小成本法,评价了以声诺维为造影剂的增强超声(CE-US)检查与增强CT(CE- CT)在肝脏局灶性病变诊断中的成本-效果。结果显示,两者诊断的阳性正确率和阴性正确率相近,而增强超声检查的成本比增强CT少31.5%.前者具有更好的成本-效果。

关键词：成本-效果造影剂