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Chronic hepatitis C,atherosclerosis and cardiovascular disease: What impact of direct-acting antiviral treatments?

World Journal of Gastroenterology 2018年第41期24卷 4617-4621页

作者： luigi elio adinolfi Luca Rinaldi Riccardo Nevola Department of Medical SurgicalNeurologicalMetabolicand Geriatric SciencesUniversity of Campania "L.Vanvitelli"

Hepatitis C virus (HCV) infection is associated with extrahepatic manifestations, among these there is an increased risk of atherosclerosis and cardiovascular disease as well as an increased cardiovascular mortality. Several direct and indirect HCV pro-atherogenic mechanisms have been proposed. HCV lives and replicates within carotid plaques, promoting a local environment of pro-atherogenic factors. In addition, it causes conditions such as insulin resistance, diabetes, hepatic steatosis, cryoglobulinemia and endotoxinemia that are associated with the development of atherosclerosis and cardiovascular disease. Therapeutic regimens based on direct-acting antiviral agents (DAA) are currently available with high efficacy in HCV clearance and improvement of liver disease, but does HCV eradication also improve atherosclerosis and the risk of cardiovascular disease? Recently, a multi-center study has shown that elimination of HCV improves carotid atherosclerosis. Two studies have shown that DAA treatments significantly reduce the risk of cardiovascular events. Several studies have assessed the impact of HCV clearance on pro-atherosclerosis metabolic conditions showing improvement in cardiovascular risk biomarkers, disappearance or improvement of insulin resistance, reduction of risk of developing diabetes and improvement of glycemic control. There are also evidences that HCV clearance promotes the recovery of cytokines and inflammatory markers associated with atherosclerosis and the disappearance of cryoglobulinemia. Available data show that clearance of HCV by DAAs is associated with an improvement in atherosclerosis and metabolic and immunological conditions that promote the development of cardiovascular disease. However, the data are not sufficient to allow definitive conclusions and further studies will be needed to definitively clarify the impact of HCV clearance on atherosclerosis and cardiovascular disease.

关键词： Direct-acting antiviral agents Hepatitis C virus Atherosclerosis Insulin resistance Cardiovascular disease

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Predictors of early and late hepatocellular carcinoma recurrence

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World Journal of Gastroenterology 2023年第8期29卷 1243-1260页

作者： Riccardo Nevola Rachele Ruocco Livio Criscuolo Angela Villani Maria Alfano Domenico Beccia Simona Imbriani Ernesto Claar Domenico Cozzolino Ferdinando Carlo Sasso Aldo Marrone luigi elio adinolfi Luca Rinaldi Department of Advanced Medical and Surgical Sciences University of Campania“Luigi Vanvitelli”Naples 80138Italy Internal Medicine and Hepatology Unit Ospedale Evangelico BetaniaNaples 80147Italy

Hepatocellular carcinoma(HCC)is the most frequent liver neoplasm,and its incidence rates are constantly *** the availability of potentially curative treatments(liver transplantation,surgical resection,thermal ablation),long-term outcomes are affected by a high recurrence rate(up to 70%of cases 5 years after treatment).HCC recurrence within 2 years of treatment is defined as“early”and is generally caused by the occult intrahepatic spread of the primary neoplasm and related to the tumor burden.A recurrence that occurs after 2 years of treatment is defined as“late”and is related to de novo HCC,independent of the primary *** HCC recurrence has a significantly poorer prognosis and outcome than late *** pathogenesis corresponds to different predictors of the risk of early or late *** adequate knowledge of predictive factors and recurrence risk stratification guides the therapeutic strategy and post-treatment *** at high risk of HCC recurrence should be referred to treatments with the lowest recurrence rate and when standardized to combined or adjuvant therapy *** review aimed to expose the recurrence predictors and examine the differences between predictors of early and late recurrence.

关键词： Hepatocellular carcinoma Early recurrence Late recurrence Predictors Liver transplant Liver resection Thermal ablation

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Non-alcoholic fatty liver disease:beyond the liver is an emerging multifaceted systemic disease

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Hepatobiliary Surgery and Nutrition 2018年第2期7卷 143-146页

作者： luigi elio adinolfi Aldo Marrone Luca Rinaldi Department of Medical SurgicalNeurologicalMetabolic and Geriatric SciencesUniversity of Campania"Luigi Vanvitelli"NaplesItaly

Non-alcoholic fatty liver disease(NAFLD)has become the most frequent liver disease in the world and is characterized by an accumulation of intrahepatic triglycerides above 5%of hepatocytes in the absence of significan... 详细信息

关键词： liver NAFLD beyond

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Impact of chronic liver disease on SARS-CoV-2 infection outcomes:Roles of stage,etiology and vaccination

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World Journal of Gastroenterology 2023年第5期29卷 800-814页

作者： Riccardo Nevola Livio Criscuolo Domenico Beccia Augusto Delle Femine Rachele Ruocco Simona Imbriani Maria Alfano Angela Villani Antonio Russo Pasquale Perillo Raffaele Marfella luigi elio adinolfi Ferdinando Carlo Sasso Aldo Marrone Luca Rinaldi Department of Advanced Medical and Surgical Sciences University of Campania“Luigi Vanvitelli”Naples 80138Italy Internal Medicine and Hepatology Unit Ospedale Evangelico BetaniaNaples 80147Italy Department of Mental Health and Public Medicine University of Campania“Luigi Vanvitelli”Naples 80138Italy

Since the first identification in December of 2019 and the fast spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,it has represented a dramatic global public health *** affecting mainly the respiratory system,SARS-CoV-2 disease,defined as coronavirus disease 2019(COVID-19),may have a systemic involvement leading to multiple organ *** evidence about the SARS-CoV-2 tropism for the liver and the increasing of hepatic cytolysis enzymes during infection support the presence of a pathophysiological relationship between liver and *** the other side,patients with chronic liver disease have been demonstrated to have a poor prognosis with *** particular,patients with liver cirrhosis appear extremely vulnerable to ***,the etiology of liver disease and the vaccination status could affect the COVID-19 *** review analyzes the impact of the disease stage and the related causes on morbidity and mortality,clinical outcomes during SARS-CoV-2 infection,as well as the efficacy of vaccination in patients with chronic liver disease.

关键词： SARS-CoV-2 infection COVID-19 Chronic liver disease Cirrhosis Nonalcoholic fatty liver disease Liver injury

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Nonalcoholic fatty liver disease: Evolving paradigms

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World Journal of Gastroenterology 2017年第36期23卷 6571-6592页

作者： Amedeo Lonardo Fabio Nascimbeni Mauro Maurantonio Alessandra Marrazzo Luca Rinaldi luigi elio adinolfi Azienda Ospedaliero-Universitaria di Modena Ospedale Civile di Baggiovara University of Modena and Reggio Emilia Department of Medical SurgicalNeurologicalGeriatricand Metabolic SciencesUniversity of Campania“Luigi Vanvitelli”

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 *** has such an epidemic prevalence as to make it impossible to screen general population looking for NAFLD ***,focusing on those cohorts of individuals exposed to the highest risk of NAFLD could be a more rational ***,which can be diagnosed with either non-invasive strategies or through liver biopsy,is a pathogenically complex and clinically heterogeneous *** existence of metabolic as opposed to genetic-associated disease,notably including"lean NAFLD"has recently been ***,NAFLD is a systemic condition,featuring metabolic,cardiovascular and(hepatic/extrahepatic)cancer *** the clinico-laboratory features of NAFLD we discuss hyperuricemia,insulin resistance,atherosclerosis,gallstones,psoriasis and selected endocrine *** 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 ***,lifestyle changes and drug treatment options to be implemented in the individual patient are also critically *** conclusion,this review emphasizes the new concepts on clinical and pathogenic heterogeneity of NAFLD,a systemic disorder with a multifactorial pathogenesis and protean clinical *** 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.

关键词： Nonalcoholic fatty liver disease Biomarkers Clinical correlates Diagnosis Epidemiology Genetics Liver histology Management Metabolic Syndrome Pathogenesis Screening Type 2 diabetes

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Mechanisms and clinical behavior of hepatocellular carcinoma in HBV and HCV infection and alcoholic and non-alcoholic fatty liver disease

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Hepatoma Research 2018年第9期4卷 45-66页

作者： Riccardo Nevola Luca Rinaldi Mauro Giordano Aldo Marrone luigi elio adinolfi Department of Medical SurgicalNeurologicalMetabolicand Geriatric SciencesUniversity of Campania'L.Vanviteli'Division of Internal MedicinePiazza MiragliaNaples 80138Italy

Hepatocellular carcinoma (HCC) is the main tumor of the liver and is the sixth most frequently diagnosed tumor in the world. It is the evolution of chronic hepatic injury secondary to different etiologies. Chronic hepatitis B virus and hepatitis C virus infection, chronic alcoholic hepatitis, as well as non-alcoholic fatty liver disease are the most common causes behind the development of HCC. The introduction of effective prophylaxis and treatment against hepatitis B, the recent use of highly effective hepatitis C treatments, as well as lifestyle changes observed in recent decades in the general population causing an increase in obesity and metabolic syndrome have led to significant epidemiological change in HCC in relation to the changed etiologic prevalence of liver injury. Increasing evidence was emerging, emphasizing how the development of HCC is a complex and multifactorial process. The knowledge of the molecular mechanisms involved is important for the understanding of the basic factors of the development of hepatocarcinogenesis and of possible therapeutic approaches. Several pathogenic mechanisms and clinical expression of HCC occur in relation to the different etiologies of the underlying liver disease. The different clinical behavior of HCC often makes diagnosis difficult at an early stage, that is necessary for an effective therapeutic approach. This review analyzes the possible different pathogenic mechanisms involved in the development of HCC and emphasizes the different epidemiological and clinical aspects of HCC observed in the most common forms of liver diseases of viral and non-viral origin.

关键词： Hepatocellular carcinoma hepatitis C virus hepatitis B virus alcohol hepatitis non-alcoholic fatty liver disease

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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

AIM To characterize natural history of cryptogenic cirrhosis(CC) and compare its clinical features and outcomes to those of hepatitis C virus(HCV)-related *** 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 *** 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 *** Undiagnosed no

关键词：肝肝硬化 Hepatocellular 癌新陈代谢的症候群不含酒精的脂肪肝疾病心血管的疾病

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Hepatitis B virus burden in developing countries

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World Journal of Gastroenterology 2015年第42期21卷 11941-11953页

作者： Rosa Zampino Adriana Boemio Caterina Sagnelli Loredana Alessio luigi elio adinolfi Evangelista Sagnelli Nicola Coppola Department of Medical Surgical Neurological Metabolic and Geriatric Sciences Second University of Naples Department of Clinical and Experimental Medicine and Surgery "F. Magrassi e A. Lanzara" Second University of Naples Section of Infectious Diseases Department of Mental Health and Public Medicine Second University of Naples Department of Mental Health and Public Medicine Second University of Naples

Hepatitis B virus(HBV) infection has shown an intermediate or high endemicity level in low-income countries over the last five decades. In recent years, however, the incidence of acute hepatitis B and the prevalence of hepatitis B surface antigen chronic carriers have decreased in several countries because of the HBV universal vaccination programs started in the nineties. Some countries, however, are still unable to implement these programs, particularly in their hyperendemic rural areas. The diffusion of HBV infection is still wide in several low-income countries where the prevention, management and treatment of HBV infection are a heavy burden for the governments and healthcare authorities. Of note, the information on the HBV epidemiology is scanty in numerous eastern European and Latin-American countries. The studies on molecular epidemiology performed in some countries provide an important contribution for a more comprehensive knowledge of HBV epidemiology, and phylogenetic studies provide information on the impact of recent and older migratory flows.

关键词： Hepatitis B virus Molecular epidemiology Preventio

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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 ***,therefore,is associated with HCV infection by necessity rather than by chance ***6%of HCV patients have ***,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 ***,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 *** 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 *** data,moreover,suggest that HCV-steatosis contributes to premature atherogenesis via both direct and indirect *** 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 dy

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Chronic hepatitis C virus infection and neurological and psychiatric disorders:An overview

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World Journal of Gastroenterology 2015年第8期21卷 2269-2280页

作者： luigi elio adinolfi Riccardo Nevola Giacomo Lus Luciano Restivo Barbara Guerrera Ciro Romano Rosa Zampino Luca Rinaldi Ausilia Sellitto Mauro Giordano Aldo Marrone Clinical Hospital of Marcianise Second University of Naples Department of Medical Surgical Neurological Geriatric and Metabolic Sciences Second University of Naples Neurological Sciences Second University of Naples

Hepatitis C virus(HCV)infection is considered a systemic disease because of involvement of other organs and tissues concomitantly with liver *** the extrahepatic manifestations,neuropsychiatric disorders have been reported in up to 50%of chronic HCV infected *** the central and peripheral nervous system may be involved with a wide variety of clinical *** HCV-associated neurological conditions include cerebrovascular events,encephalopathy,myelitis,encephalomyelitis,and cognitive impairment,whereas"brain fog",depression,anxiety,and fatigue are at the top of the list of psychiatric ***,HCV infection is known to cause both motor and sensory peripheral neuropathy in the context of mixed cryoglobulinemia,and has also been recently recognized as an independent risk factor for *** extrahepatic manifestations are independent of severity of the underlying chronic liver disease and hepatic *** brain is a suitable site for HCV replication,where the virus may directly exert neurotoxicity;other mechanisms proposed to explain the pathogenesis of neuropsychiatric disorders in chronic HCV infection include derangement of metabolic pathways of infected cells,alterations in neurotransmitter circuits,autoimmune disorders,and cerebral or systemic inflammation.A pathogenic role for HCV is also suggested by improvement of neurological and psychiatric symptoms in patients achieving a sustained virologic response following interferon treatment;however,further ad hoc trials are needed to fully assess the impact of HCV infection and specific antiviral treatments on associated neuropsychiatric disorders.

关键词： Hepatitis C virus Neurological disorders Psychiatr

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