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Chronic hepatitis C virus infection and atherosclerosis: Clinical impact and mechanisms

World Journal of Gastroenterology 2014年第13期20卷 3410-3417页

作者： luigi e adinolfi Rosa Zampino Luciano Restivo Amedeo Lonardo Barbara Guerrera Aldo Marrone Fabio Nascimbeni Anna Florio Paola Loria Department of Medical SurgicalNeurologicalMetabolicand Geriatric SciencesSecond University of Naples80100 NaplesItaly Department of Internal Medicine EndocrinologyMetabolism and GeriatricsUniversity of Modena and Reggio Emilia41126 Modena Italy Vascular Surgery Second University of Naples80100 NaplesItaly

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 *** of published studies supports the view that HCV infection should be considered a risk factor for the development of carotid atherosclerosis,heart failure and *** contrast,findings from studies addressing coronary artery disease and HCV have yielded conflicting ***,meta-analytic reviews and prospective studies are *** pathogenic mechanisms connecting HCV infection,chronic liver disease,and atherogenesis are not completely ***,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 *** 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 ***,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.

关键词： Hepatitis C virus Atherosclerosis Coronary artery disease Stroke Inflammation

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All-oral interferon-free treatments:The end of hepatitis C virus story,the dream and the reality

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World Journal of Hepatology 2015年第22期7卷 2363-2368页

作者： luigi e adinolfi Barbara Guerrera Department of Medical SurgicalNeurologicalGeriatric and Metabolic SciencesSecond University of Naples

The year 2014 marked the beginning of the end of the interferon era and the triumph of the all-oral interferon-free regimens for treatment of hepatitis C virus(HCV) infection. These innovative therapies are safe and yield a cure rate of over 90%. The scientifichepatology community is euphoric about the possibility of elimination and even eradication of HCV infection. However,the current high cost of the new all-oral regimens allows access to treatment only for a restricted number of HCV-infected patients. In addition,many other conditions such as modality of access and delivery of care,inadequate knowledge of HCV epidemiology and political commitments to be undertaken,hamper the fulfillment of the dream to eliminate the virus. Since,such conditions are not impossible to overcome,a global urgent effort must be made to allow a widespread access to the new treatments which will permit in the next years to avoid million of HCV-related deaths.

关键词： Sofosbuvir Simeprevir New-oral hepatitis C virus t

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Chronic HCV infection and inflammation:Clinical impact on hepatic and extra-hepatic manifestations

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World Journal of Hepatology 2013年第10期5卷 528-540页

作者： Rosa Zampino Aldo Marrone Luciano Restivo Barbara Guerrera Ausilia Sellitto Luca Rinaldi Ciro Romano luigi e adinolfi Division of Internal Medicine and Hepatology Second University of Naples Polyclinic Hospital Division of Internal Medicine Second University of NaplesClinical Hospital of MarcianiseCaserta Local Health Unit Division of Internal Medicine Allergy and Clinical ImmunologySecond University of Naples Polyclinic Hospital

The liver has a central role in regulating inflammation by its capacity to secrete a number of proteins that control both local and systemic inflammatory responses. Chronic inflammation or an exaggerated inflammatory response can produce detrimental effects on target organs. Chronic hepatitis C virus(HCV) infection causes liver inflammation by complex and not yet well-understood molecular pathways, including direct viral effects and indirect mechanisms involving cytokine pathways,oxidative stress and steatosis induction. An increasing body of evidence recognizes the inflammatory response in chronic hepatitis C as pathogenically linked to the development of both liver-limited injury(fibrosis, cirrhosis and hepatocellular carcinoma) and extrahepatic HCV-related diseases(lymphoproliferative disease,atherosclerosis, cardiovascular and brain disease). Defining the complex mechanisms of HCV-induced inflammation could be crucial to determine the global impact of infection, to estimate progression of the disease, and to explore novel therapeutic approaches to avert HCVrelated diseases. This review focuses on HCV-related clinical conditions as a result of chronic liver and systemic inflammatory states.

关键词： Hepatitis C virus Inflammation Cytokines Oxidative stress Hepatic disease extra-hepatic diseases

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

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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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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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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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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 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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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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Accretion and jet power in active galactic nuclei

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Research in Astronomy and Astrophysics 2011年第11期11卷 1266-1278页

作者： luigi Foschini INAF-Osservatorio Astronomico di Brera Via E. Bianchi 46 23807 Merate (LC) Italy

The classical diagrams of radio loudness and jet power as a function of mass and accretion rate of the central spacetime singularity in active galactic nuclei are reanalyzed by including the data of the recently discovered powerful relativistic jets in Narrow-Line Seyfert 1 Galaxies. The results are studied in the light of the known theories of relativistic jets, indicating that, although the Blandford-Znajek mechanism is sufficient to explain the power radiated by BL Lac Objects, it falls to completely account for the power from quasars and Narrow-Line Seyfert 1 Galaxies. This favors the scenario outlined by Cavaliere ＆ D＇elia of a composite jet, with a magnetospheric core plus a hydromagnetic component emerging when the accretion power increases and the disk becomes radiation-pressure dominated. A comparison with Galactic compact objects is also made, finding some striking similarities, indicating that since neutron stars are low-mass jet systems analogous to black holes, Narrow-Line Seyfert 1 Galaxies are low-mass counterparts of blazars.

关键词： galaxies jets-BL Lacertae objects general-quasars general-galaxies Seyfert

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