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| 1 | Oxidative stress:New insights on the association of nonalcoholic fatty liver disease and atherosclerosis显示文摘Non-alcoholic fatty liver disease(NAFLD) represents the most common and emerging chronic liver disease worldwide. It includes a wide spectrum of liver diseasesranging from simple fatty liver to non-alcoholic steatohepatitis(NASH),which may progress to fibrosis and more severe liver complications such as cirrhosis,hepatocellular carcinoma and liver mortality. NAFLD is strongly associated with obesity,insulin resistance,hypertension,and dyslipidaemia,and is now regarded as the liver manifestation of the metabolic syndrome. The increased mortality of patients with NAFLD is primarily a result of cardiovascular disease and,to a lesser extent,to liver related diseases. Increased oxidative stress has been reported in both patients with NAFLD and patient with cardiovascular risk factors. Thus,oxidative stress represents a shared pathophysiological disorder between the two conditions. Several therapeutic strategies targeting oxidative stress reduction in patients with NAFLD have been proposed,with conflicting results. In particular,vitamin E supplementation has been suggested for the treatment of non-diabetic,non-cirrhotic adults with active NASH,although this recommendation is based only on the results of a single randomized controlled trial. Other antioxidant treatments suggested are resveratrol,silybin,L-carnitine and pentoxiphylline. No trial so far,has evaluated the cardiovascular effects of antioxidant treatment in patients with NAFLD. New,large-scale studies including as end-point also the assessment of the atherosclerosis markers are needed. | Licia Polimeni Maria Del Ben Francesco Baratta Ludovica Perri Fabiana Albanese Daniele Pastori Francesco Violi Francesco Angelico | 2015 | World Journal of Hepatology2015，7，10： | 23 |
| 2 | 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 |
| 3 | Association between non-alcoholic fatty liver disease and obstructive sleep apnea显示文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is an emerging liver disease and currently the most common cause of incidental abnormal liver tests.The pathogenesis of NAFLD is multifactorial and many mechanisms that cause fatty liver infiltration,inflammation,oxidative stress and progressive fibrosis have been proposed.Obstructive sleep apnea(OSA)may be linked with the pathogenesis and the severity of NAFLD.AIM To study the association between NAFLD and OSA considering also the efficacy of continuous positive airway pressure(CPAP)treatment.METHODS A Pub Med search was conducted using the terms'non-alcoholic fatty liver disease AND(obstructive sleep apnea OR obstructive sleep disorders OR sleep apnea)'.Research was limited to title/abstract of articles published in English in the last 5 years;animal and child studies,case reports,commentaries,letters,editorials and meeting abstracts were not considered.Data were extracted on a standardized data collection table which included:First author,publication year,country,study design,number of patients involved,diagnosis and severity of OSA,diagnosis of NAFLD,patient characteristics,results of the study.RESULTSIn total,132 articles were initially retrieved on Pub Med search and 77 in the last five years.After removal of irrelevant studies,13 articles were included in the qualitative analysis.There was a total of 2753 participants across all the studies with a mean age between 42 and 58 years.The proportion of males ranged from21%to 87.9%and the mean body mass index ranged from 24.0 to 49.9 kg/m2.The results of this review showed an increased prevalence of NAFLD in patients with diagnosis of OSA,even in the absence of coexisting comorbidities such as obesity or metabolic syndrome.Furthermore,the severity of NAFLD is associated with the increase in OSA severity.Effective CPAP treatment,although not always decisive,may stabilize or slow NAFLD progression with benefits on metabolic and cardiovascular functions.CONCLUSION In NAFLD patients,although asymptomatic,it is recommended to systematically perform polysomnography in order to early and better treat them before the development of potentially life threatening systemic dysfunctions. | Ilaria Umbro Valerio Fabiani Mario Fabiani Francesco Angelico Maria Del Ben | 2020 | World Journal of Gastroenterology2020，26，20： | 10 |
| 4 | Modern approach to the clinical management of non-alcoholic fatty liver disease显示文摘Non-alcoholic fatty liver disease(NAFLD)is the most common and emerging form of chronic liver disease worldwide.It includes a wide spectrum of liver diseases ranging from simple fatty liver to steatohepatitis,which may progress to cirrhosis,liver cancer,and liver mortality.Common metabolic diseases,which are well established cardiovascular risk factors,have been associated to NAFLD and cardiovascular disease is the single most important cause of morbidity and mortality in this patient population.The pathogenesis of NAFLD appears multifactorial and many mechanisms have been proposed as possible causes of fatty liver infiltration.Management of fatty liver has become a major challenge to healthcare systems as the consequence of the increasing rates of obesity worldwide.First-line management focuses on lifestyle modifications.Moderate weight reduction either by dietary restriction or by increased habitual physical activity is safe and highly recommended.Several therapeutic interventions have been proposed.These include insulin sensitizer agents,lipid lowering drugs,antioxidants such as vitamin E and supplementation of vitamin D3.However,therapeutic strategies have been largely empirical so far,and experimental trials have mostly been carried out in uncontrolled settings with small sample sizes.Metabolic conditions such as diabetes mellitus,obesity,hypertension and hyperlipidemia,should be strongly considered and a multidisciplinary approach should be personalized for individual patients.Treatment of co-morbidities should be regarded as of paramount importance in the management of these patients.The purpose of this review is to examine different approaches for the clinical management of non-alcoholic fatty liver disease. | Maria Del Ben Licia Polimeni Francesco Baratta Daniele Pastori Lorenzo Loffredo Francesco Angelico | 2014 | World Journal of Gastroenterology2014，20，26： | 8 |
| 5 | Moving forward in the treatment of cholangiocarcinoma显示文摘Despite being the second most frequent primary liver tumor in humans,early diagnosis and treatment of cholangiocarcinoma(CCA)are still unsatisfactory.In fact,survival after 5 years is expected in less than one fourth of patients diagnosed with this disease.Rare incidence,late appearance of symptoms and heterogeneous biology are all factors contributing to our limited knowledge of this cancer and determining its poor prognosis in the clinical setting.Several efforts have been made in the last decades in order to achieve an improved classification/understanding with regard to the diverse CCA forms.Location within the biliary tree has helped to distinguish between intrahepatic,perihilar and distal CCA types.Sequence analysis contributed to identifying several characteristic genetic aberrations in CCA that may also serve as possible targets for therapy.Novel findings are expected to significantly improve the management of this malignancy in the near future.In this changing scenario our review focuses on the current and future strategies for CCA treatment.Both systemic and surgical treatments are discussed in detail.The results of the main studies in this field are reported,together with the ongoing trials.The current findings suggest that an integrated multidisciplinary approach to this malignancy would be helpful to improve its outcome. | Tommaso M Manzia Alessandro Parente Ilaria Lenci Bruno Sensi Martina Milana Carlo Gazia Alessandro Signorello Roberta Angelico Giuseppe Grassi Giuseppe Tisone Leonardo Baiocchi | 2021 | World Journal of Gastrointestinal Oncology2021，13，12： | 6 |
| 6 | De novo malignancies after liver transplantation: The effect of immunosuppression-personal data and review of literature显示文摘BACKGROUND Immunosuppression has undoubtedly raised the overall positive outcomes in the post-operative management of solid organ transplantation. However, long-term exposure to immunosuppression is associated with critical systemic morbidities. De novo malignancies following orthotopic liver transplants (OLTs) are a serious threat in pediatric and adult transplant individuals. Data from different experiences were reported and compared to assess the connection between immunosuppression and de novo malignancies in liver transplant patients. AIM To study the role of immunosuppression on the incidence of de novo malignancies in liver transplant recipients. METHODS A systematic literature examination about de novo malignancies and immunosuppression weaning in adult and pediatric OLT recipients was described in the present review. Worldwide data were collected from highly qualified institutions performing OLTs. Patient follow-up, immunosuppression discontinuation and incidence of de novo malignancies were reported. Likewise, the review assesses the differences in adult and pediatric recipients by describing the adopted immunosuppression regimens and the different type of diagnosed solid and blood malignancy.RESULTS Emerging evidence suggests that the liver is an immunologically privileged organ able to support immunosuppression discontinuation in carefully selected recipients. Malignancies are often detected in liver transplant patients undergoing daily immunosuppression regimens. Post-transplant lymphoproliferative diseases and skin tumors are the most detected de novo malignancies in the pediatric and adult OLT population, respectively. To date, immunosuppression withdrawal has been achieved in up to 40% and 60% of well-selected adult and pediatric recipients, respectively. In both populations, a clear benefit of immunosuppression weaning protocols on de novo malignancies is difficult to ascertain because data have not been specified in most of the clinical experiences. CONCLUSION The selected populations of tolerant pediatric and adult liver transplant recipients greatly benefit from immunosuppression weaning. There is still no strong clinical evidence on the usefulness of immunosuppression withdrawal in OLT recipients on malignancies. An interesting focus is represented by the complete reconstitution of the immunological pathways that could help in decreasing the incidence of de novo malignancies and may also help in treating liver transplant patients suffering from cancer. | Tommaso Maria Manzia Roberta Angelico Carlo Gazia Ilaria Lenci Martina Milana Oludamilola T Ademoyero Domiziana Pedini Luca Toti Marco Spada Giuseppe Tisone Leonardo Baiocchi | 2019 | World Journal of Gastroenterology2019，25，35： | 3 |
| 7 | Impact of immunosuppression minimization and withdrawal in long-term hepatitis C virus liver transplant recipients显示文摘AIM:To investigate the effects of different immunosuppressive regimens and avoidance on fibrosis progression in hepatitis C virus(HCV)liver transplant(LT)recipients.METHODS:We retrospectively compared the liver biopsies of well-matched HCV LT recipients under calcineurin inhibitors(CNI group,n=21)and mycophenolate(MMF group,n=15)monotherapy,with those patients who successfully withdrawn immunosuppression(IS)therapy from at least 3 years(TOL group,n=10).To perform the well-matched analysis,all HCV transplanted patients from December 1993 were screened.Only those HCV patients who reached the following criteria were considered for the analysis:(1)at least3 years of post-operative follow-up;(2)patients with normal liver graft function under low dose CNI monotherapy(CNI group);(3)patients with normal liver graft function under antimetabolite(Micophenolate Mofetil or coated mycophenolate sodium)monotherapy(MMF group);and(4)recipients with normal liver function without any IS.We excluded from the analysis recipients who were IS free or under monotherapy for<36 mo,recipients with cirrhosis or with unstable liver function tests.RESULTS:Thirty six recipients were enrolled in the study.Demographics,clinical data,time after LT and baseline liver biopsies were comparable in the three groups.After six years of follow-up,there was no worsening of hepatic fibrosis in the MMF group(2.5±1.5Ishak Units vs 2.9±1.7 Ishak Units,P=0.5)and TOL group(2.7±10.7 vs 2.5±1.2,P=0.2).In contrast,a significant increase in the fibrosis score was observed in the CNI group(2.2±1.7 vs 3.9±1.6,P=0.008).The yearly fibrosis progression rate was significantly worse in the CNI group(0.32±0.35)vs MMF group(0.03±0.31,P=0.03),and TOL group(-0.02±0.27,P=0.02).No differences have been reported in grading scores for CNI group(2.79±1.9,P=0.7),MMF group(3.2±1.5,P=0.9)and TOL group(3.1±1.4,P=0.2).Twenty four patients were treated with low dose ribavirin(8TOL,7 MMF,9 CNI).The hepatitis C titers were comparable in the three groups.No episodes of rejection have been reported despite differences of liver function test in the three groups during the observational period.CONCLUSION:IS withdrawal and MMF monotherapy is safe and seems to be associated with the slowest fibrosis progression in HCV LT recipients. | Tommaso Maria Manzia Roberta Angelico Paolo Ciano Jon Mugweru Kofi Owusu Daniele Sforza Luca Toti Giuseppe Tisone | 2014 | World Journal of Gastroenterology2014，20，34： | 3 |
| 8 | Sofosbuvir plus daclatasvir for post-transplant recurrent hepatitis C: potent antiviral activity but no clinical benefit if treatment is given late显示文摘 | Adriano M. Pellicelli Marzia Montalbano Raffaella Lionetti Christine Durand Peter Ferenci Gianpiero D’Offizi Viola Knop Andrea Telese Ilaria Lenci Arnaldo Andreoli Stefan Zeuzem Mario Angelico | 2014 | Digestive and Liver Disease2014，，： | 2 |
| 9 | Chronic rejection after liver transplantation:Opening the Pandora’s box显示文摘Chronic rejection(CR)of liver allografts causes damage to intrahepatic vessels and bile ducts and may lead to graft failure after liver transplantation.Although its prevalence has declined steadily with the introduction of potent immunosuppressive therapy,CR still represents an important cause of graft injury,which might be irreversible,leading to graft loss requiring re-transplantation.To date,we still do not fully appreciate the mechanisms underlying this process.In addition to T cell-mediated CR,which was initially the only recognized type of CR,recently a new form of liver allograft CR,antibody-mediated CR,has been identified.This has indeed opened an era of thriving research and renewed interest in the field.Liver biopsy is needed for a definitive diagnosis of CR,but current research is aiming to identify new non-invasive tools for predicting patients at risk for CR after liver transplantation.Moreover,the minimization or withdrawal of immunosuppressive therapy might influence the establishment of subclinical CR-related injury,which should not be disregarded.Therapies for CR may only be effective in the“early”phases,and a tailored management of the immunosuppression regimen is essential for preventing irreversible liver damage.Herein,we provide an overview of the current knowledge and research on CR,focusing on early detection,identification of non-invasive biomarkers,immunosuppressive management,re-transplantation and future perspectives of CR. | Roberta Angelico Bruno Sensi Tommaso M Manzia Giuseppe Tisone Giuseppe Grassi Alessandro Signorello Martina Milana Ilaria Lenci Leonardo Baiocchi | 2021 | World Journal of Gastroenterology2021，27，45： | 2 |
| 10 | The Tor Vergata weaning off immunosuppression protocol in stable HCV liver transplant patients: The updated follow up at 78 months显示文摘 | Giuseppe Orlando Tommaso Manzia Leonardo Baiocchi Alberto Sanchez-Fueyo Mario Angelico Giuseppe Tisone | 2008 | Transplant Immunology2008，，1： | 2 |
| 11 | Obstructive sleep apnoea syndrome and the metabolic syndrome in an internal medicine setting显示文摘 | Francesco Angelico Maria del Ben Teresa Augelletti Rosanna de Vita Rocco Roma Francesco Violi Mario Fabiani | 2010 | European Journal of Internal Medicine2010，，3： | 1 |
| 12 | Drugs improving insulin resistance for non-alcoholic fatty liver disease and/or non-alcoholic steatohepatitis显示文摘 | Angelico F Burattin M Alessandri C | 2007 | Cochrane Database Syst Rev2007，24，00： | 1 |
| 13 | Treatment of a patient with congenital analbuminemia with atorvastatin and albumin infusion显示文摘Congenital analbuminemia is a rare autosomic recessive inherited disorder characterized by low plasma albumin and hypercholesterolemia, which may increase cardiovascular risk. Patients are essentially asymptomatic, apart from ease of fatigue, minimal ankle oedema and hypotension. There is no accepted strategy for safely treating both hypercholesterolemia and analbuminemia in order to eventually decrease the atherosclerotic risk. We report a case of congenital analbuminemia(1.0 g/dL) in a 38-year-old male with hypercholesterolemia(range: 406-475 mg/dL) and severe arterial dysfunction [no brachial artery flow-mediated dilation(FMD)]. Long-term, cholesterol-lowering treatment with atorvastatin was associated with the appearance of peripheral edema. Twomonths of infusion with albumin improved FMD(7%) and reduced serum cholesterol(273 mg/dL), supporting the hypothesis of a compensatory role of hypercholesterolemia. Statin treatment, together with periodical albumin infusions, may contribute to the safe reduction of cardiovascular risk. | Maria Del Ben Francesco Angelico Lorenzo Loffredo Francesco Violi | 2013 | World Journal of Clinical Cases2013，1，1： | 1 |
| 14 | Hepatobiliary complications associated with total parenteral nutrition显示文摘 | Angelico M Della Guardia P | 2000 | Aliment Pharmacol Ther2000，14，2： | 1 |
| 15 | Insulin Resistance, the Metabolic Syndrome, and Nonalcoholic Fatty Liver Disease显示文摘 | F Angelico M Del Ben R Conti S Francioso K Feole S Fiorello M G. Cavallo B Zalunardo F Lirussi C Alessandri F Violi | 2005 | The Journal of Clinical Endocrinology & Metabolism2005，，3： | 1 |
| 16 | Lipomatous angiomyo- fibroblastoma of the vulva: diagnostic and histogenetic considera- tions显示文摘 | Magro G Salvatorelli L Angelico G | 2014 | Pathologica2014，106，4： | 1 |
| 17 | Chronic liver disease in the Alexandria governorate, Egypt: contribution of schistosomiasis and hepatitis viruis factions显示文摘 | Angelico M Renganathan E Gandin C | 1997 | Hepatol1997，26，2： | 1 |
| 18 | Effect of cyclooxygenase inhibi-tors on the micturition reflex in rats:correlation with inhibition of cycloox-ygenase isoenzymes显示文摘 | Angelico P Guarneri L Velasco C | 2006 | BJU Int2006，97，4： | 1 |
| 19 | Insulin resistance, the metabolic syndrome, and nonalcoholic fatty liver disease 显示文摘 | Angelico F Del BM Gonti R | 2005 | J C/in Endocrinol Metab2005，90，3： | 1 |
| 20 | Failure of a reinforced triple course of hepatitis B vaccination in patients transplanted for HBV-related cirrhosis 显示文摘 | Angelico M Di Paolo D Trinito MO | 2002 | Hepatology2002，35，1： | 1 |
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