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| 1 | Risk of cardiovascular,cardiac and arrhythmic complications in patients with non-alcoholic fatty liver disease显示文摘Non-alcoholic fatty liver disease(NAFLD)has emerged as a public health problem of epidemic proportions worldwide.Accumulating clinical and epidemiological evidence indicates that NAFLD is not only associated with liver-related morbidity and mortality but also with an increased risk of coronary heart disease(CHD),abnormalities of cardiac function and structure(e.g.,left ventricular dysfunction and hypertrophy,and heart failure),valvular heart disease(e.g.,aortic valve sclerosis)and arrhythmias(e.g.,atrial fibrillation).Experimental evidence suggests that NAFLD itself,especially in its more severe forms,exacerbates systemic/hepatic insulin resistance,causes atherogenic dyslipidemia,and releases a variety of pro-inflammatory,pro-coagulant and pro-fibrogenic mediators that may play important roles in the pathophysiology of cardiac and arrhythmic complications.Collectively,these findings suggest that patients with NAFLD may benefit from more intensive surveillance and early treatment interventions to decrease the risk for CHD and other cardiac/arrhythmic complications.The purpose of this clinical review is to summarize the rapidly expanding body of evidence that supports a strong association between NAFLD and cardiovascular,cardiac and arrhythmic complications,to briefly examine the putative biological mechanisms underlying this association,and to discuss some of the current treatment options that may influence both NAFLD and its related cardiac and arrhythmic complications. | Stefano Ballestri Amedeo Lonardo Stefano Bonapace Christopher D Byrne Paola Loria Giovanni Targher | 2014 | World Journal of Gastroenterology2014，20，7： | 55 |
| 2 | Nonalcoholic fatty liver disease: Evolving paradigms显示文摘In the last years new evidence has accumulated on nonalcoholic fatty liver disease(NAFLD)challenging the paradigms that had been holding the scene over the previous 30 years.NAFLD has such an epidemic prevalence as to make it impossible to screen general population looking for NAFLD cases.Conversely,focusing on those cohorts of individuals exposed to the highest risk of NAFLD could be a more rational approach.NAFLD,which can be diagnosed with either non-invasive strategies or through liver biopsy,is a pathogenically complex and clinically heterogeneous disease.The existence of metabolic as opposed to genetic-associated disease,notably including'lean NAFLD'has recently been recognized.Moreover,NAFLD is a systemic condition,featuring metabolic,cardiovascular and(hepatic/extrahepatic)cancer risk.Among the clinico-laboratory features of NAFLD we discuss hyperuricemia,insulin resistance,atherosclerosis,gallstones,psoriasis and selected endocrine derangements.NAFLD is a precursor of type 2 diabetes(T2D)and metabolic syndrome and progressive liver disease develops in T2D patients in whom the course of disease is worsened by NAFLD.Finally,lifestyle changes and drug treatment options to be implemented in the individual patient are also critically discussed.In conclusion,this review emphasizes the new concepts on clinical and pathogenic heterogeneity of NAFLD,a systemic disorder with a multifactorial pathogenesis and protean clinical manifestations.It is highly prevalent in certain cohorts of individuals who are thus potentially amenable to selective screening strategies,intensive follow-up schedules for early identification of liver-related and extrahepatic complications and in whom earlier and more aggressive treatment schedules should be carried out whenever possible. | Amedeo Lonardo Fabio Nascimbeni Mauro Maurantonio Alessandra Marrazzo Luca Rinaldi Luigi Elio Adinolfi | 2017 | World Journal of Gastroenterology2017，23，36： | 33 |
| 3 | Nonalcoholic fatty liver disease and aging: Epidemiology to management显示文摘Nonalcoholic fatty liver disease(NAFLD) is common in the elderly, in whom it carries a more substantial burden of hepatic(nonalcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma) and extra-hepatic manifestations and complications(cardiovascular disease, extrahepatic neoplasms) than in younger age groups. Therefore, proper identification and management of this condition is a major task for clinical geriatricians and geriatric hepatologists. In this paper, the epidemiology and pathophysiology of this condition are reviewed, and a full discussion of the link between NAFLD and the aspects that are peculiar to elderly individuals is provided; these aspects include frailty, multimorbidity, polypharmacy and dementia. The proper treatment strategy will have to consider the peculiarities of geriatric patients, so a multidisciplinary approach is mandatory. Non-pharmacological treatment(diet and physical exercise) has to be tailored individually considering the physical limitations of most elderly people and the need for an adequate caloric supply. Similarly, the choice of drug treatment must carefully balance the benefits and risks in terms of adverse events and pharmacological interactions in the common context of both multiple health conditions and polypharmacy. In conclusion, further epidemiological and pathophysiological insight is warranted. More accurate understanding of the molecular mechanisms of geriatric NAFLD will help in identifying the most appropriate diagnostic and therapeutic approach for individual elderly patients. | Marco Bertolotti Amedeo Lonardo Chiara Mussi Enrica Baldelli Elisa Pellegrini Stefano Ballestri Dante Romagnoli Paola Loria | 2014 | World Journal of Gastroenterology2014，20，39： | 15 |
| 4 | Fatty liver,carotid disease and gallstones:A study of age-related associations显示文摘AIM: To evaluate carotid intima-media thickening (IMT) and plaques, gallstone disease (GD) and fatty liver (FL) as a function of age. METHODS: In 449 subjects, FL and carotid disease were assessed ultrasonographically. In a subgroup of 65/449 patients with non-alcoholic fatty liver disease (NAFLD), carotid disease, GD and associated factors were determined. RESULTS: FL of unspecified etiology was more common in younger and GD in older individuals. FL subjects had an increased prevalence of IMT and a decreased prevalence of plaques and manifested carotid disease earlier. Plaques were more common in subjects with GD. Age was an independent predictor of carotid disease outcome and FL was a protective factor for plaques. In NAFLD, there was an inverse correlation between body weight and age and the latter independently predicted carotid findings. CONCLUSION: Cardiovascular risk in patients with FL and NAFLD needs to be assessed as a function of age and body weight. | Amedeo Lonardo Silvia Lombardini Federica Scaglioni Stefano Ballestri Anna Maria Verrone Marco Bertolotti Lucia Carulli Dorval Ganazzi Nicola Carulli Paola Loria | 2006 | World Journal of Gastroenterology2006，12，36： | 14 |
| 5 | Pathogenesis and significance of hepatitis C virus steatosis:An update on survival strategy of a successful pathogen显示文摘Hepatitis C virus(HCV)is a successful pathogen on the grounds that it exploits its host’s metabolism to build up viral particles;moreover it favours its own survival by inducing chronic disease and the development of specific anatomic changes in the infected organ.Steatosis,therefore,is associated with HCV infection by necessity rather than by chance alone.Approximately6%of HCV patients have steatohepatitis.Interestingly,HCV steatosis occurs in the setting of multiple metabolic abnormalities(hyperuricemia,reversible hypocholesterolemia,insulin resistance,arterial hypertension and expansion of visceral adipose tissue)collectively referred to as'hepatitis C-associated dysmetabolic syndrome'(HCADS).General,nonalcoholic fatty liver disease(NAFLD)-like,mechanisms of steatogenesis(including increased availability of lipogenic substrates and de novo lipogenesis;decreased oxidation of fatty substrates and export of fatty substrates)are shared by all HCV genotypes.However,genotype 3 seemingly amplifies such steatogenic molecular mechanisms reported to occur in NAFLD via more profound changes in microsomal triglyceride transfer protein;peroxisome proliferator-activated receptor alpha;sterol regulatory element-binding proteins and phosphatase and tensin homologue.HCV steatosis has a remarkable clinical impact in as much as it is an acknowledged risk factor for accelerated fibrogenesis;for impaired treatment response to interferon and ribavirin;and development of hepatocellular carcinoma.Recent data,moreover,suggest that HCV-steatosis contributes to premature atherogenesis via both direct and indirect mechanisms.In conclusion,HCV steatosis fulfills all expected requirements necessary to perpetuate the HCV life cycle.A better understanding of the physiology of HCADS will likely result in a more successful handling of disease with improved antiviral success rates. | Amedeo Lonardo Luigi Elio Adinolfi Luciano Restivo Stefano Ballestri Dante Romagnoli Enrica Baldelli Fabio Nascimbeni Paola Loriaca | 2014 | World Journal of Gastroenterology2014，20，23： | 14 |
| 6 | Nerve growth factor involvement in liver cirrhosis and hepatocellular carcinoma显示文摘AIM: To define NGF (nerve growth factor) and its high- affinity receptor trkANGF presence and distribution in fibrotic liver and in HCC, and to verify if NGF might have a role in fibrosis and HCC. METHODS: Intracellular distribution of NGF and trkANGF were assessed by immunohistochemistry and immuno- electron microscopy in liver specimens from HCC, cirrhosis or both. ELISA was used to measure circulating NGF levels. RESULTS: NGF and trkANGF were highly expressed in HCC tissue, mainly localized in hepatocytes, endothelial and some Kupffer cells. In the cirrhotic part of the liver they were also markedly expressed in bile ducts epithelial and spindle-shaped cells. Surprisingly, in cirrhotic tissue from patients without HCC, both NGF and trkANGF were negative. NGF serum levels in cirrhotic and/or HCC patient were up to 25-fold higher than in controls. CONCLUSION: NGF was only detected in liver tissue with HCC present. Intracellular distribution suggests paracrine and autocrine mechanisms of action. Better definition of mechanisms may allow for therapeutic and diagnostic/prognostic use of NGF. | Guido Rasi Annalucia Serafino Lia Bellis Maria Teresa Lonardo Federica Andreola Manuela Zonfrillo Giovanni Vennarecci Pasquale Pierimarchi Paola Sinibaldi Vallebona Giuseppe Maria Ettorre Eugenio Santoro Claudio Puoti | 2007 | World Journal of Gastroenterology2007，13，37： | 13 |
| 7 | Chronic hepatitis C virus infection and atherosclerosis: Clinical impact and mechanisms显示文摘Hepatitis C virus(HCV)infection represents a major health issue worldwide due to its burden of chronic liver disease and extrahepatic manifestations including cardiovascular diseases,which are associated with excess mortality.Analysis of published studies supports the view that HCV infection should be considered a risk factor for the development of carotid atherosclerosis,heart failure and stroke.In contrast,findings from studies addressing coronary artery disease and HCV have yielded conflicting results.Therefore,meta-analytic reviews and prospective studies are warranted.The pathogenic mechanisms connecting HCV infection,chronic liver disease,and atherogenesis are not completely understood.However,it has been hypothesized that HCV may promote atherogenesis and its complications through several direct and indirect biological mechanisms involving HCV colonization and replication within arterial walls,liver steatosis and fibrosis,enhanced and imbalanced secretion of inflammatory cytokines,oxidative stress,endotoxemia,mixed cryoglobulinemia,perturbed cellular and humoral immunity,hyperhomocysteinemia,hypo-adiponectinaemia,insulin resistance,type 2 diabetes and other components of the metabolic syndrome.Understanding these complex mechanisms is of fundamental importance for the development of novel therapeutic approaches to prevent and to treat vascular complications in patients with chronic HCV infection.Currently,it seems that HCV clearance by interferon and ribavirin treatment significantly reduces non-liver-related mortality;moreover,interferon-based treatment appears to decrease the risk of ischemic stroke. | Luigi E Adinolfi Rosa Zampino Luciano Restivo Amedeo Lonardo Barbara Guerrera Aldo Marrone Fabio Nascimbeni Anna Florio Paola Loria | 2014 | World Journal of Gastroenterology2014，20，13： | 6 |
| 8 | Clinical features and natural history of cryptogenic cirrhosis compared to hepatitis C virus-related cirrhosis显示文摘AIM To characterize natural history of cryptogenic cirrhosis(CC) and compare its clinical features and outcomes to those of hepatitis C virus(HCV)-related cirrhosis.METHODS A prospective cohort of 102 consecutive patients at their first diagnosis of CC were enrolled in this study. The clinical data and outcomes were compared to an ageand Child-pugh class-matched cohort of 110 patients with HCV-related cirrhosis. Diagnosis of cirrhosis was based on compatible clinical and laboratory parameters, ultrasound/endoscopic parameters and, whenever possible, on histological grounds and transient elastography. All cases of cirrhosis without a definite etiology were enrolled in the CC group. The parameters assessed were:(1) severity of liver disease at the time of first diagnosis;(2) liver decompensation during follow-up;(3) hepatocellular carcinoma(HCC);(4) orthotopic liver transplantation; and(5) death. The independent associated factors were evaluated by multiple logistic regression analysis, and survival and its determinants by the Kaplan-Meier model, log-rank test and Cox regression.RESULTS At the first observation, median age was 66 and 65 years and male gender was 36% and 58% for CC and HCV cirrhosis, respectively. CC showed Child-pugh class A/B/C of 47%/31%/22%, respectively. Compared to HCV cirrhosis, CC exhibited a significantly higher prevalence of metabolic syndrome(12% vs 54%, respectively), overweight/obesity, high BMI, impaired glucose tolerance, high blood pressure, dyslipidemia, hyperuricemia, cardiovascular diseases, extrahepatic cancer, and gallstones. Over a median period of 42 mo of follow-up, liver decompensation, HCC development and death for CC and HCV-related cirrhosis were 60.8%, and 54.4%, 16.7% and 17.2%, 39.2% and 30%, respectively. The median survival was 60 mo for CC. Independent predictors of death were age and Childpugh class at diagnosis. CC showed an approximately twofold higher incidence of HCC in Child-pugh class A.CONCLUSION Undiagnosed nonalcoholic fatty liver disease has an etiologic role in CC that is associated with a poor prognosis, early HCC development, high risk of cardiovascular disease and extrahepatic cancer. | Luca Rinaldi Fabio Nascimbeni Mauro Giordano Chiara Masetti Barbara Guerrera Annalisa Amelia Maria Chiara Fascione Stefano Ballestri Dante Romagnoli Rosa Zampino Riccardo Nevola Enrica Baldelli Natalina Iuliano Valerio Rosato Amedeo Lonardo Luigi Elio Adinolfi | 2017 | World Journal of Gastroenterology2017，23，8： | 5 |
| 9 | Ultrasonographic fatty liver indicator, a novel score which rules out NASH and is correlated with metabolic parameters in NAFLD显示文摘 | Stefano Ballestri Amedeo Lonardo Dante Romagnoli Lucia Carulli Luisa Losi Christopher P. Day Paola Loria | 2012 | Liver Int2012，，8： | 4 |
| 10 | Fatty liver is associated with an increased risk of diabetes and cardiovascular disease- Evidence from three different disease models: NAFLD, HCV and HIV显示文摘Fatty liver, which frequently coexists with necroinflammatory and fibrotic changes, may occur in the setting of nonalcoholic fatty liver disease(NAFLD) and chronic infections due to either hepatitis C virus(HCV) or human immunodeficiency virus(HIV). These three pathologic conditions are associated with an increased prevalence and incidence of cardiovascular disease(CVD) and type 2 diabetes(T2D). In this multidisciplinary clinical review, we aim to discuss the ever-expanding wealth of clinical and epidemiological evidence supporting a key role of fatty liver in the development of T2 D and CVD in patients with NAFLD and in those with HCV or HIV infections. For each of these three common diseases, the epidemiological features, pathophysiologic mechanisms and clinical implications of the presence of fatty liver in predicting the risk of incident T2 D and CVD are examined in depth. Collectively, the data discussed in this updated review, which follows an innovative comparative approach, further reinforce the conclusion that the presence of fatty/inflamed/fibrotic liver might be a shared important determinant for the development of T2 D and CVD in patients with NAFLD, HCV or HIV. This review may also open new avenues in the clinical and research arenas and paves the way for the planning of future, well-designed prospective and intervention studies. | Amedeo Lonardo Stefano Ballestri Giovanni Guaraldi Fabio Nascimbeni Dante Romagnoli Stefano Zona Giovanni Targher | 2016 | World Journal of Gastroenterology2016，22，44： | 4 |
| 11 | Chronic HCV infection is a risk of atherosclerosis. Role of HCV and HCV-related steatosis显示文摘 | Luigi E. Adinolfi Luciano Restivo Rosa Zampino Barbara Guerrera Amedeo Lonardo Laura Ruggiero Francesco Riello Paola Loria Anna Florio | 2012 | Atherosclerosis2012，，2： | 3 |
| 12 | Metabolic alterations and chronic hepatitis C: treatment strategies显示文摘 | Luigi E Adinolfi Luciano Restivo Rosa Zampino Amedeo Lonardo Paola Loria | 2011 | Expert Opinion on Pharmacotherapy2011，，14： | 3 |
| 13 | From NAFLD in clinical practice to answers from guidelines显示文摘 | Fabio Nascimbeni Raluca Pais Stefano Bellentani Christopher Paul Day Vlad Ratziu Paola Loria Amedeo Lonardo | 2013 | Journal of Hepatology2013，，： | 3 |
| 14 | Clinical and molecular spectrum of Wiedemann-Steiner syndrome, an emerging member of the chromatinopathy family显示文摘Wiedemann-Steiner syndrome(OMIM#605130)is a rare congenital malformation syndrome characterized by hypertrichosis cubiti associated with short stature;consistent facial features,including long eyelashes,thick or arched eyebrows with a lateral flare,wide nasal bridge,and downslanting and vertically narrow palpebral fissures;mild to moderate intellectual disability;behavioral difficulties;and hypertrichosis on the back.It is caused by heterozygous pathogenic variants in KMT2A.This gene has an established role in histone methylation,which explains the overlap of Wiedemann-Steiner syndrome with other chromatinopathies,a heterogeneous group of syndromic conditions that share a common trigger:The disruption of one of the genes involved in chromatin modification,leading to dysfunction of the epigenetic machinery. | Paolo Fontana Francesco Fioravanti Passaretti Marianna Maioli Giuseppina Cantalupo Francesca Scarano Fortunato Lonardo | 2020 | World Journal of Medical Genetics2020，9，1： | 2 |
| 15 | Chronic HCV infection is a risk of atherosclerosis. Role of HCV and HCV-related steatosis显示文摘 | Luigi E. Adinolfi Luciano Restivo Rosa Zampino Barbara Guerrera Amedeo Lonardo Laura Ruggiero Francesco Riello Paola Loria Anna Florio | 2012 | Atherosclerosis2012，，2： | 2 |
| 16 | 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 |
| 17 | Cardiovascular and Systemic Risk in Nonalcoholic Fatty Liver Disease - Atherosclerosis as a Major Player in the Natural Course of NAFLD显示文摘 | Amedeo Lonardo Silvia Sookoian Michel Chonchol Paola Loria Giovanni Targher | 2013 | Current Pharmaceutical Design2013，，29： | 2 |
| 18 | Combined endoscopic and surgical management of Dieulafoy vascular malformation显示文摘 | GRISENDI A LONARDO A CASCI GD | 1994 | J Am Coll Surg1994，179，5： | 1 |
| 19 | Should nonalcoholic fatty liver disease be renamed?显示文摘 | Loria P Lonardo A Carulli N | 2005 | Dig Dis2005，23，： | 1 |
| 20 | Nonalcoholic fatty liver disease(NAFLD)and cardiovascular disease:an open question显示文摘 | Loria P Lonardo A Bellentani S | | 0，，： | 1 |
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