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Reduced lysosomal acid lipase activity: A new marker of liver disease severity across the clinical continuum of non-alcoholic fatty liver disease?

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World Journal of Gastroenterology 2019年第30期25卷 4172-4180页

作者： francesco Baratta Daniele Pastori Domenico Ferro Giovanna Carluccio Giulia Tozzi francesco angelico francesco Violi Maria Del Ben Department of Internal Medicine and Medical Specialties Sapienza-University of RomeRome 00155Italy Hepatogastroenterology and Nutrition Unit-Pediatric Department Bambino GesùChildren’s HospitalRome 00156Italy Department of Public Health and Infectious Disease Sapienza-University of RomeRome 00161Italy

Lysosomal acid lipase(LAL)plays a key role in intracellular lipid metabolism.Reduced LAL activity promotes increased multi-organ lysosomal cholesterol ester storage,as observed in two recessive autosomal genetic diseases,Wolman disease and Cholesterol ester storage disease.Severe liver steatosis and accelerated liver fibrosis are common features in patients with genetic LAL deficiency.By contrast,few reliable data are available on the modulation of LAL activity in vivo and on the epigenetic and metabolic factors capable of regulating its activity in subjects without homozygous mutations of the Lipase A gene.In the last few years,a less severe and non-genetic reduction of LAL activity was reported in children and adults with non-alcoholic fatty liver disease(NAFLD),suggesting a possible role of LAL reduction in the pathogenesis and progression of the disease.Patients with NAFLD show a significant,progressive reduction of LAL activity from simple steatosis to non-alcoholic steatohepatitis and cryptogenic cirrhosis.Among cirrhosis of different etiologies,those with cryptogenic cirrhosis show the most significant reductions of LAL activity.These findings suggest that the modulation of LAL activity may become a possible new therapeutic target for patients with more advanced forms of NAFLD.Moreover,the measurement of LAL activity may represent a possible new marker of disease severity in this clinical setting.

关键词： Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Lysosomal acid lipase Cirrhosis Wolman disease Cholesterol ester storage disease

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Association between non-alcoholic fatty liver disease and obstructive sleep apnea

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World Journal of Gastroenterology 2020年第20期26卷 2669-2681页

作者： Ilaria Umbro Valerio Fabiani Mario Fabiani francesco angelico Maria Del Ben Department of Anatomical HistologicalForensic Medicine and Orthopedic SciencesSapienza University of RomeRome 00161Italy Department of Neurosciences Mental Health and Sensory OrgansSapienza University of RomeRome 00123Italy Department of Sense Organs Sapienza University of RomeRome 00161Italy Department of Public Health and Infectious Diseases Sapienza University of RomeRome 00161Italy Department of Clinical InternalAnesthetic and Cardiovascular SciencesSapienza University of RomeRome 00161Italy

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 recom

关键词： Continuous positive air pressure Non-alcoholic fatty liver disease Nonalcoholic steatohepatitis Obstructive sleep apnea Obstructive sleep disorders Sleep apnea

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Treatment of a patient with congenital analbuminemia with atorvastatin and albumin infusion

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World Journal of Clinical Cases 2013年第1期1卷 44-48页

作者： Maria Del Ben francesco angelico Lorenzo Loffredo francesco Violi Clinica Medica I Sapienza University 00161 Rome Italy

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.

关键词： Analbuminemia Hypercholesterolemia Atorvastatin Albumin infusion Endothelial dysfunction

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Modern approach to the clinical management of non-alcoholic fatty liver disease

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World Journal of Gastroenterology 2014年第26期20卷 8341-8350页

作者： Maria Del Ben Licia Polimeni francesco Baratta Daniele Pastori Lorenzo Loffredo francesco angelico Department of Internal Medicine and Medical Specialities Department of Public Health and Infectious Diseases Sapienza University

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.

关键词： Non-alcoholic fatty liver disease Nonalcoholic ste

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Oxidative stress:New insights on the association of nonalcoholic fatty liver disease and atherosclerosis

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World Journal of Hepatology 2015年第10期7卷 1325-1336页

作者： Licia Polimeni Maria Del Ben francesco Baratta Ludovica Perri Fabiana Albanese Daniele Pastori francesco Violi francesco angelico Department of Public Health and Infectious Diseases Sapienza University of Rome Department of Internal Medicine and Medical Specialties Sapienza University of Rome

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.

关键词： Cardiovascular disease Oxidative stress Non-alcoholic fatty liver disease Atherosclerosis Nonalcoholicsteatohepatitis

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Uterine large cell neuroendocrine carcinoma with unusual colonic metastasis

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Journal of Cancer Metastasis and Treatment 2017年第1期3卷 144-149页

作者： Antonio Ieni Giuseppe angelico Rosalba De Sarro francesco Fleres Antonio Macrì Giovanni Tuccari Department of Human Pathology of Adult and Evolutive Age“Gaetano Barresi” Section of Anatomic PathologyUniversity of Messina98125 MessinaItaly Student in Medicine and Surgery University of Messina98125 MessinaItaly Department of Human Pathology of Adult and Evolutive Age“Gaetano Barresi” Section of General SurgeryUniversity of MessinaAzienda Ospedaliera Universitaria“Policlinico Gaetano Martino”98125 MessinaItaly.

A 78-year-old female patient arrived at our practice complaining of progressive abdominal increase and presenting a clinical picture of intestinal obstruction.At physical examination,the abdomen appeared distended,moderately painful with the presence of a mass of hard consistency.Abdominal computed tomography scan showed a large hypodense pelvic mass that indicated a compression and lateral deviation of the uterus and bladder.Microscopically,the mass showed a uniform solid pattern,composed of medium and large-sized cells with hyperchromatic and pleomorphic nuclei demonstrating high mitotic activity and diffuse immunoreactivity for estrogen receptors and synaptophysin.A diagnosis of uterine poorly differentiated large cell neuroendocrine carcinoma,arising in the endometrium with an unusual colonic metastatic localization,was made.

关键词： Neuroendocrine carcinoma metastasis uterus differential diagnosis immunohistochemistry

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