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Hepatitis C virus and metabolic disorder interactions towards liver damage and atherosclerosis

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World Journal of Gastroenterology 2014年第11期20卷 2825-2838页

作者： Umberto Vespasiani-Gentilucci paolo gallo Antonio De Vincentis Giovanni Galati Antonio Picardi Internal Medicine and Hepatology Unit University Campus Bio-Medico of Rome00128 RomeItaly

Hepatitis C virus (HCV) is one of the main causes of liver disease worldwide, and alterations of glucose metabolism have reached pandemic proportions in western countries. However, the frequent coexistence between these two conditions is more than simply coincidental, since HCV can induce insulin resistance through several mechanisms. Indeed, the virus interferes with insulin signaling both directly and indirectly, inducing the production of pro-inflammatory cytokines. Furthermore, the entire viral life cycle has strict interconnections with lipid metabolism, and HCV is responsible for a “viral” steatosis which is frequently superimposed to a “metabolic” one. Several evidences suggest that HCV-induced metabolic disorders contribute both to the evolution of liver fibrosis and, likely, to the progression of the other disorders which are typically associated with altered metabolism, in particular atherosclerosis. In the present review, we will examine in depth the links between HCV infection and insulin resistance, liver steatosis and diabetes, and analyze the impact of these interactions on the progression of liver fibrosis and atherosclerosis. Special attention will be focused on the highly debated topic of the relationship between HCV infection and cardiovascular disease. The available clinical literature on this item will be broadly reviewed and all the mechanisms possibly implied will be discussed.

关键词： Hepatitis C virus Metabolism Insulin resistance Diabetes mellitus Steatosis Fibrosis Atherosclerosis Cardiovascular risk

Thrombocytopenia in chronic liver disease:Physiopathology and new therapeutic strategies before invasive procedures

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World Journal of Gastroenterology 2022年第30期28卷 4061-4074页

作者： paolo gallo Francesca Terracciani Giulia Di Pasquale Matteo Esposito Antonio Picardi Umberto Vespasiani-Gentilucci Clinical Medicine and Hepatology Unit Campus Bio-Medico UniversityRoma 00128Italy

Chronic liver disease is characterized by several hematological derangements resulting in a complex and barely rebalanced haemostatic *** is the most common abnormality observed in these patients and recent advances have led to researchers focus the attention on the multifactorial origin of thrombocytopenia and on the key role of thrombopoietin(TPO)in its *** thrombocytopenia(platelet count<50000/μL)complicates the management of patients with chronic liver disease by increasing the potential risk of bleeding for invasive procedures,which may be therefore delayed or canceled even if *** the very last years,the development of new drugs which exceed the limits of the current standard of care(platelet transfusions,either immediately before or during the procedure)paves the way to a new scenario in the management of this population of *** agents,such as the TPOreceptor agonists avatrombopag and lusutrombopag,have been developed in order to increase platelet production as an alternative to platelet *** agents have demonstrated a good profile in terms of efficacy and safety and will hopefully allow reducing limitations and risks associated with platelet transfusion,without any delay in scheduled ***,it is expected that patients with chronic liver disease will be able to face invasive procedures with one more string in their bow.

关键词： Thrombocytopenia Chronic liver disease Thrombopoietin agonists Platelet transfusions Avatrombopag Lusutrombopag

Promoting genetics in non-alcoholic fatty liver disease: Combined risk score through polymorphisms and clinical variables

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World Journal of Gastroenterology 2018年第43期24卷 4835-4845页

作者： Umberto Vespasiani-Gentilucci paolo gallo Chiara Dell' Unto Mara Volpentesta Raffaele Antonelli-Incalzi Antonio Picardi Unit of Internal Medicine and Hepatology Department of Medicine University Campus Bio-Medico

Non-alcoholic fatty liver disease(NAFLD) has a prevalence of approximately 30% in western countries, and is emerging as the first cause of liver cirrhosis and hepatocellular carcinoma(HCC). Therefore, risk stratification emerges as fundamental in order to optimize human and economic resources, and genetics displays intrinsic characteristics suitable to fulfill this task. According to the available data, heritability estimates for hepatic fat content range from 20% to 70%, and an almost 80% of shared heritability has been found between hepatic fat content and fibrosis. The rs738409 single nucleotide polymorphism(SNP) in patatin-like phospholipase domain-containing protein 3 gene and the rs58542926 SNP in transmembrane 6 superfamily member 2 gene have been robustly associated with NAFLD and with its progression, but promising results have been obtained with many other SNPs. Moreover, there has been proof of the additive role of the different SNPs in determining liver damage, and there have been preliminary experiences in which risk scores created through a few genetic variants, alone or in combination with clinical variables, were associated with a strongly potentiated risk of NAFLD, non-alcoholic steatohepatitis(NASH), NASH fibrosis or NAFLD-HCC. However, to date, clinical translation of genetics in the field of NAFLD has been poor or absent. Fortunately, the research we have done seems to have placed us on the right path: We should rely on longitudinal rather than on cross-sectional studies; we should focus on relevant outcomes rather than on simple liver fat accumulation; and we should put together the genetic and clinical information. The hope is that combined genetic/clinical scores, derived from longitudinal studies and built on a few strong genetic variants and relevant clinical variables, will reach a significant predictive power, such as to have clinical utility for risk stratification at the single patient level and even to esteem the impact of intervention

关键词： Non-alcoholic fatty liver disease Single nucleotide polymorphism Patatin-like phospholipase domain-containing protein 3 Transmembrane 6 superfamily member 2 Membrane bound O-acyltransferasedomain containing 7 Glucokinase regulatory gene Risk score Non-alcoholic steatohepatitis Non-alcoholic steatohepatitis cirrhosis Hepatocellular carcinoma

Approaching the Sarcopenic Patient with Nonalcoholic Steatohepatitis-related Cirrhosis

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Journal of Clinical and Translational Hepatology 2024年第3期12卷 278-286页

作者： paolo gallo Valentina Flagiello Andrea Falcomatà Giulia Di Pasquale Giorgio D’Avanzo Francesca Terracciani Antonio Picardi Umberto Vespasiani-Gentilucci Operative Research Unit of Clinical Medicine and Hepatology Fondazione Policlinico Universitario Campus Bio-MedicoVia Alvaro del PortilloRomaItaly Research Unit of Hepatology Department of Medicine and SurgeryUniversitàCampus Bio-Medico di RomaVia Alvaro del PortilloRomaItaly

Sarcopenia is a well-known complication of chronic liver disease(CLD),and it is almost always observed in patients with cirrhosis,at least in those with decompensated *** nonalcoholic fatty liver disease(NAFLD),recently renamed metabolic dysfunction-associated steatotic liver disease(MASLD),is becoming the leading cause of end-stage liver disease,a new scenario characterized by the frequent coexistence of NAFLD,obesity,and sarcopenia is *** it is not yet resolved whether the bidirectional relationship between sarcopenia and NAFLD subtends causal determinants,it is clear that the interaction of these two conditions is associated with an increased risk of poor ***,during the course of CLD,deregulation of the liver-muscle-adipose tissue axis has been ***,owing to the lack of properly designed studies,specific therapeutic guidelines for patients with sarcopenia in the context of NAFLD-related CLD have not yet been *** aimed to induce the loss of fat mass together with the maintenance of lean body mass seem most *** can be achieved by properly designed diets integrated with specific nutritional supplementations and accompanied by adequate physical *** studies aiming to add to the knowledge of the correct assessment and approach to sarcopenia in the context of NAFLD-related CLD are eagerly awaited.

关键词： NAFLD MASLD Cirrhosis Sarcopenia Sarcopenic obesity

Percutaneous electrochemotherapy in the treatment of portal vein tumor thrombosis at hepatic hilum in patients with hepatocellular carcinoma in cirrhosis: A feasibility study

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World Journal of Gastroenterology 2017年第5期23卷 906-918页

作者： Luciano Tarantino Giuseppina Busto Aurelio Nasto Raffaele Fristachi Luigi Cacace Maria Talamo Catello Accardo Sara Bortone paolo gallo paolo Tarantino Riccardo Aurelio Nasto Matteo Nicola Dario Di Minno Pasquale Ambrosino Department of Surgery Interventional Hepatology UnitAndrea Tortora Hospital Department of Oncology Andrea Tortora Hospital Department of Surgery Unit of General Surgery and OncologyAndrea Tortora Hospital Department of Pathology Andrea Tortora Hospital Department of Radiology Andrea Tortora Hospital Department of Advanced Biomedical Sciences Division of CardiologyFederico II University Unit of Cell and Molecular Biology in Cardiovascular Diseases Centro Cardiologico MonzinoIRCCS Department of Clinical Medicine and Surgery Federico II University

AIMTo treated with electrochemotherapy (ECT) a prospective case series of patients with liver cirrhosis and Vp3-Vp4- portal vein tumor thrombus (PVTT) from hepatocellular carcinoma (HCC), in order to evaluate the feasibility, safety and efficacy of this new non thermal ablative technique in those *** patients (5 males and 1 female), aged 61-85 years (mean age, 70 years), four in Child-Pugh A and two in Child-Pugh B class, entered our study series. All patients were studied with three-phase computed tomography (CT), contrast enhanced ultrasound (CEUS) and ultrasound-guided percutaneous biopsy of the thrombus before ECT. All patients underwent ECT treatment (Cliniporator Vitae®, IGEA SpA, Carpi, Modena, Italy) of Vp3-Vp4 PVTT in a single session. At the end of the procedure a post-treatment biopsy of the thrombus was performed. Scheduled follow-up in all patients entailed: CEUS within 24 h after treatment; triphasic contrast-enhanced CT and CEUS at 3 mo after treatment and every six months ***-treatment CEUS showed complete absence of enhancement of the treated thrombus in all cases. Post-treatment biopsy showed apoptosis and necrosis of tumor cells in all cases. The follow-up ranged from 9 to 20 mo (median, 14 mo). In 2 patients, the follow-up CT and CEUS demonstrated complete patency of the treated portal vein. Other 3 patients showed a persistent avascular non-tumoral shrinked thrombus at CEUS and CT during follow-up. No local recurrence was observed at follow-up CT and CEUS in 5/6 patients. One patient was lost to follow-up because of death from gastrointestinal hemorrage 5 wk after *** patients with cirrhosis, ECT seems effective and safe for curative treatment of Vp3-Vp4 PVTT from HCC.

关键词： Hepatocellular carcinoma Portal vein tumor thrombosis Electrochemotherapy

Hepatitis C treatment in the elderly:New possibilities and controversies towards interferon-free regimens

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World Journal of Gastroenterology 2015年第24期21卷 7412-7426页

作者： Umberto Vespasiani-Gentilucci Giovanni Galati paolo gallo Antonio De Vincentis Elisabetta Riva Antonio Picardi Internal Medicine and Hepatology Unit University Campus Bio-Medico Virology Unit University Campus Bio-Medico

Due to the progressive aging of the hepatitis C virus(HCV) population which have acquired the infection during its maximum spread after the Second World War, the management of the elderly HCV-infected patient is emerging as a hot topic. Unfortunately, although it is recognized that the progression of HCV-related liver disease gets faster with aging, and that even extrahepatic manifestations of HCV infection are probably worse in the elderly, till now, treatment attempts in this population have been significantly limited by the wellknown contraindications and side effects of interferon(IFN). The arrival of several new anti-HCV drugs, and the possibility to combine them in safe and effective anti-viral regimens, is relighting the hope of a cure for many elderly patients who had been cut out of IFN-based treatments. However, although these new regimens will be certainly more manageable, it should be underscored that IFN-free doesn't mean free from any contraindication or side-effect. Moreover, one issue which promises to become central is that of the possible interactions between antiviral therapy and the multiple drugs frequently assumed by elderly patients because of comorbidities. In this review, we will revise the epidemiology pointing to HCV as an infection of the elderly, the evidences that HCV harms the health of the aged patient more than that of the young one, and the available experiences of HCV treatment in the elderly with the "old" IFN-based regimens and with the newer drugs. We will conclude that the availability of IFNfree regimens should prompt us to change our mind and consider a significantly larger number of possible candidates among elderly patients, who would take significant advantage from viral eradication. Rather than the anagraphic age, drug-drug interactions and, mainly in case of economic restrictions, an evaluation of life expectancy dependent on liver disease with respect to that dependent on comorbidities, are likely to be the key issues g

关键词： Hepatitis C virus Elderly Interferon Ribavirin Telaprevir Boceprevir Sofosbuvir Simeprevir Daclatasvir Side effects Drug-drug interactions

Non-cirrhotic portal hypertension with large regenerative nodules: A diagnostic challenge

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World Journal of Gastroenterology 2011年第20期17卷 2580-2584页

作者： Umberto Vespasiani Gentilucci paolo gallo Giuseppe Perrone Riccardo Del Vescovo Giovanni Galati Sandro Spataro Chiara Mazzarelli Adriano Pellicelli Antonella Afeltra Antonio Picardi Clinical Medicine and Hepatology Unit University Campus Bio-Medico of Rome Clinical Pathology University Campus Bio-Medico of Rome Department of Radiology University Campus Bio-Medico of Rome Hepatology Unit San Camillo-Forlanini Hospital

Non-cirrhotic portal hypertension is a poorly understood condition characterized by portal hypertension in the absence of conventional hepatic cirrhosis and described in association with blood coagulation disorders, myeloproliferative and immunological diseases and with exposure to toxic drugs. Very recently, precise classification criteria have been proposed in order to define four distinct subcategories. The present case highlights how the clinical presentation, the confounding results from imaging studies, and the difficulties in the histological evaluation often render cases of non-cirrhotic portal hypertension a real diagnostic challenge. It also underscores the classification problems which can be faced once this diagnosis is performed. Indeed, the different subcategories proposed result from the prevalent subtypes in a spectrum of hepatic regenerative responses to a variety of injuries determining microcirculatory dis-turbances. More flexibility in classification should derive from this etiopathogenic background.

关键词： Non-cirrhotic portal hypertension Large regenerative nodules Nodular regenerative hyperplasia

Single-cell pan-omics, environmental neurology, and artificial intelligence:the time for holistic brain health research

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Neural Regeneration Research 2025年第6期20卷 1703-1704页

作者： paolo Abondio Francesco Bruno IRCCS Istituto delle Scienze Neurologiche di Bologna BolognaItaly Association for Neurogenetic Research(ARN) Lamezia TermeCatanzaroItaly

The brain,with its trillions of neural connections,different cellular types,and molecular complexities,presents a formidable challenge for researchers aiming to comprehend the multifaceted nature of neural *** traditional methods have provided valuable insights,emerging technologies offer unprecedented opportunities to delve deeper into the underpinnings of brain *** the everevolving landscape of neuroscience,the quest to unravel the mysteries of the human brain is bound to take a leap forward thanks to new technological improvements and bold interpretative frameworks.

关键词： function artificial landscape

Higher production of tumor necrosis factor alpha in hemozoin-fed human adherent monocytes is dependent on lipidic component of malarial pigment:new evidences on cytokine regulation in Plasmodium falciparum malaria

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Asian Pacific Journal of Tropical Medicine 2010年第2期3卷 85-89页

作者： Prato Mauro gallo Valentina Arese paolo Department of Genetics Biology and BiochemistryUniversity of Torino Medical School

Objective:To investigate whether the increase of tumor necrosis factor alpha is dependent on lipidic component of malarial ***:Adherent human monocytes were fed for 3 hours with different meals(native hemozoin;lipid free hemozoin;and control latex particles),then tumor necrosis factor alpha was monitored in cell supernatants up to 48 hours through western blotting or specific enzyme-linked immunoadsorbent *** selected experiments,unfed monocytes were treated with different doses of 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid or 4-hydroxynonenal instead of ***:Hemozoin-fed monocytes produced higher levels of tumor necrosis factor alpha than unstimulated and latex-fed cells, while lipid-free hemozoin did not reproduce these ***,hemozoin effects were mimicked dose-dependently by 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid,but not by ***:Present data suggest an essential role for lipids in hemozoindependent enhanced release of tumor necrosis factor alpha from monocytes,and 15(S,R)hydroxy -6,8,11,13-eicosatetraenoic acid could be one possible specific mediator.

关键词： Hemozoin Plasmodium falciparum Malaria Monocyte Phagocytosis Tumor necrosis factor alpha(TNFalpha) 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid(15-HETE) Matrix metalloproteinase-9(MMP-9)