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Risk of cardiovascular,cardiac and arrhythmic complications in patients with non-alcoholic fatty liver disease

World Journal of Gastroenterology 2014年第7期20卷 1724-1745页

作者： stefano ballestri Amedeo Lonardo stefano Bonapace Christopher D Byrne Paola Loria Giovanni Targher Division of Internal Medicine Pavullo Hospital41026 PavulloItaly Department of Biomedical Metabolic and Neural SciencesDivision of Internal Medicine NOCSAEUniversity of Modena and Reggio Emilia and Azienda USLBaggiovara41126 ModenaItaly Division of Cardiology "Sacro Cuore" Hospital37024 NegrarItaly Southampton National Institute for Health Research Biomedical Research Centre University Hospital SouthamptonSouthampton SO16 6YDUnited Kingdom Division of Endocrinology Diabetes and MetabolismDepartment of MedicineUniversity and Azienda Ospedaliera Universitaria Integrata37126 VeronaItaly

Non-alcoholic fatty liver disease(NAFLD)has emerged as a public health problem of epidemic proportions *** 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 ***,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 *** 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.

关键词： Non-alcoholic fatty liver disease Cardiovascular disease Cardiac complications Coronary heart disease Myocardial dysfunction Valvular heart disease Arrhythmias Arrhythmic complications

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Fatty liver is associated with an increased risk of diabetes and cardiovascular disease- Evidence from three different disease models: NAFLD, HCV and HIV

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World Journal of Gastroenterology 2016年第44期22卷 9674-9693页

作者： Amedeo Lonardo stefano ballestri Giovanni Guaraldi Fabio Nascimbeni Dante Romagnoli stefano Zona Giovanni Targher Division of Internal Medicine and Metabolism Nuovo Ospedale Civile Sant'Agostino Estense - Department of Biomedical Metabolic and Neural Sciences University of Modena and Reggio Emilia and Azienda Ospedaliera of Modena Internal Medicine Pavullo Hospital Azienda Ospedaliera of Modena Section of Infectious Diseases Department of Medicine University of Modena Section of Endocrinology Diabetes and Metabolism Department of Medicine University and Azienda Ospedaliera Universitaria Integrata of Verona

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.

关键词： Atherosclerosis Cardiovascular risk Fatty liver Fibrosis Hepatitis C-associated dysmetabolic syndrome Hepatitis C virus Human immunodeficiency virus Nonalcoholic fatty liver disease Steatohepatitis Steatosis Virus-associated fatty liver disease

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Sex disparity in hepatocellular carcinoma owing to NAFLD and non-NAFLD etiology:epidemiological findings and pathobiological mechanisms

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Hepatoma Research 2020年第12期6卷 12-23页

作者： Amedeo Lonardo stefano ballestri Pierce KHChow Ayako Suzuki Operating Unit of Metabolic Syndrome Azienda Ospedaliero-Universitaria di ModenaOspedale Civile di BaggiovaraModena 41126Italy Operating Unit Internal Medicine Ospedale di PavulloAzienda UnitàSanitaria LocaleModena 41126Italy Division of Surgery and Surgical Oncology National Cancer Center Singapore and Singapore General HospitalCouncil 169610Singapore Surgery Academic Clinical Program and Office of Education Duke-NUS Medical SchoolSingapore 169857Singapore Division of Gastroenterology Duke University Health SystemDurhamNC 27710USA Division of Gastroenterology Durham VA Medical CenterDurhamNC 27705USA Programme in Cardiovascular and Metabolic Disorders Duke-NUS Medical SchoolSingapore 169857Singapore

Nonalcoholic fatty liver disease(NAFLD)exhibits sexual dimorphism,with men being more exposed than women to the risk of simple steatosis,nonalcoholic steatohepatitis fibrosis,and hepatocellular carcinoma(HCC),while the protection conferred to women seemingly disappears with aging and reproductive senescence(i.e.,menopause).HCC,the most common primary liver cancer,which carries an ominous prognosis,may result from various genetic and non-genetic risk *** is now projected to become the most common cause of *** also exhibits a definite sexual dimorphism in as much as it has a worldwide high male-to-female *** this review article,we focus on sex differences in the epidemiological features of ***,we discuss sex differences in the clinical outcome and molecular pathobiology of *** highlighting the research gaps to be filled,the aim of this review is to prompt future research of sex differences in HCC and facilitate developing personalized cancer prevention strategies,detection,and treatments to achieve better patient outcomes in NAFLD-HCC,considering sex differences in HCC pathobiology.

关键词： Liver cancer pathobiology personalized medicine sex differences

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Nonalcoholic fatty liver disease and aging: Epidemiology to management

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World Journal of Gastroenterology 2014年第39期20卷 14185-14204页

作者： Marco Bertolotti Amedeo Lonardo Chiara Mussi Enrica Baldelli Elisa Pellegrini stefano ballestri Dante Romagnoli Paola Loria Department of Biomedical Metabolic and Neural Sciences Nuovo Ospedale Civile di Modena University of Modena and Reggio Emilia and Azienda USL of Modena Baggiovara 41126 Modena Italy Division of Internal Medicine Pavullo Hospital 41026 Pavullo (MO) Italy

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.

关键词： Adipose tissue Atherosclerosis Aortic valve sclerosis Autonomic dysfunction Arrhythmia Cirrhosis Dementia Falls Frailty Hepatocellular carcinoma Microbiota Nuclear receptors Pathogenesis Sarcopenia Treatment

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Pathogenesis and significance of hepatitis C virus steatosis:An update on survival strategy of a successful pathogen

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World Journal of Gastroenterology 2014年第23期20卷 7089-7103页

作者： Amedeo Lonardo Luigi Elio Adinolfi Luciano Restivo stefano ballestri Dante Romagnoli Enrica Baldelli Fabio Nascimbeni Paola Loriaca Division of Internal Medicine Department of BiomedicalMetabolic and Neural SciencesUniversity of Modena and Reggio Emilia41126 ModenaItaly Department of Medical SurgicalNeurologicalMetabolicand Geriatric SciencesSecond University of Naples80100 NaplesItaly

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. Approximately 6% 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.

关键词： Atherosclerosis Fibrosis Hepatitis C-associated dysmetabolic syndrome Hepatocellular carcinoma Steatohepatitis Sustained virological response Hepatitis C virus

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Clinical features and natural history of cryptogenic cirrhosis compared to hepatitis C virus-related cirrhosis

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World Journal of Gastroenterology 2017年第8期23卷 1458-1468页

作者： 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 Internal Medicine Clinical Hospital of MarcianiseSecond University of Naples Department of Medical SurgicalNeurologicalMetabolicand Geriatric SciencesSecond University of Naples Outpatient Liver Clinic and Internal Medicine NOCSAEBaggiovaraAzienda USLModena Internal Medicine Pavullo HospitalAzienda Sanitaria Locale

To characterize natural history of cryptogenic cirrhosis (CC) and compare its clinical features and outcomes to those of hepatitis C virus (HCV)-related *** 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 age- and 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 *** 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 Child-Pugh class at diagnosis. CC showed an approximately twofold higher incidence of HCC in Child-Pugh class ***

关键词： Liver cirrhosis Hepatocellular carcinoma Metabolic syndrome Nonalcoholic fatty liver disease Cardiovascular diseases

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Fatty liver,carotid disease and gallstones:A study of age-related associations

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World Journal of Gastroenterology 2006年第36期12卷 5826-5833页

作者： Amedeo Lonardo Silvia Lombardini Federica Scaglioni stefano ballestri Anna Maria Verrone Marco Bertolotti Lucia Carulli Dorval Ganazzi Nicola Carulli Paola Loria University of Modena and Reggio Emilia-Azienda USL Department of Internal Medicine Metabolism Endocrinology and Geriatrics Ospedale di Baggiovara Via Giardini Modena 41100 Italy

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.

关键词： Atherosclerosis Carotid Gallstones Intimamedia thickening Fatty liver

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