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Exhaled breath analysis in hepatology: State-of-the-art and perspectives

World Journal of Gastroenterology 2019年第30期25卷 4043-4050页

作者： Antonio De Vincentis umberto vespasiani-gentilucci Anna Sabatini Raffaele Antonelli-Incalzi Antonio Picardi Unit of Clinical Medicine and Hepatology Unit of GeriatricsDepartment of MedicineCampus Bio-Medico University HospitalRome 00128Italy Unit of Electronics for sensor systems Department of EngineeringUniversity Campus Bio-Medico of RomeRome 00128Italy

Liver disease is characterized by breath exhalation of peculiar volatile organic compounds(VOCs).Thanks to the availability of sensitive technologies for breath analysis,this empiric approach has recently gained increasing attention in the context of hepatology,following the good results obtained in other fields of *** the first studies that led to the identification of selected VOCs for pathophysiological purposes,subsequent research has progressively turned towards the comprehensive assessment of exhaled breath for potential clinical *** VOC patterns were found to discriminate subjects with liver cirrhosis,to rate disease severity,and,eventually,to forecast adverse clinical outcomes even beyond existing *** results suggest that breath analysis could be useful also for detecting and staging hepatic encephalopathy and for predicting steatohepatitis in patients with nonalcoholic fatty liver ***,clinical translation is still hampered by a number of methodological limitations,including the lack of standardization and the consequent poor comparability between studies and the absence of external validation of obtained *** the low-cost and easy execution at bedside of the new technologies(e-nose),larger and well-structured studies are expected in order to provide the adequate level of evidence to support VOC analysis in clinical practice.

关键词： Exhaled breath analysis Electronic nose Gas chromatography Breath print Liver cirrhosis Nonalcoholic fatty liver disease Hepatic encephalopathy

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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

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Liver involvement in the course of thymoma-associated multiorgan autoimmunity:The first histological description

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Hepatobiliary & Pancreatic Diseases International 2022年第1期21卷 86-89页

作者： Fabrizio Citarella umberto vespasiani-gentilucci Anna Crescenzi Antonella Bianchi Vladimir Virzì Giuseppe Tonini Department of Medical Oncology Policlinico Universitario Campus Bio-Medicovia Alvaro del PortilloRome 00128Italy Area of Internal Medicine Unit of HepatologyPoliclinico Universitario Campus Bio-Medicovia Alvaro del PortilloRome 00128Italy Unit of Pathology Policlinico Universitario Campus Bio-Medicovia Alvaro del PortilloRome 00128Italy

To the Editor:Thymoma-associated multiorgan autoimmunity(TAMA)is a rare paraneoplastic syndrome described in patients with thymoma and characterized by multiorgan failure and graft-versus-host dis-ease(GVHD)like pathology affecting the skin,the gastrointestinal tract,and the *** date,only 21 cases are reported in liter-ature[1],with some patients presenting gastrointestinal and hep-atic manifestations,mainly colitis,diarrhea,and abnormal liver en-zymes,but the hepatic involvement has not been histologically characterized yet.

关键词： involvement gastrointestinal diarrhea

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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

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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

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Relationship between adipose tissue dysfunction, vitamin D deficiency and the pathogenesis of non-alcoholic fatty liver disease

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World Journal of Gastroenterology 2017年第19期23卷 3407-3417页

作者： Flavia A Cimini Ilaria Barchetta Simone Carotti Laura Bertoccini Marco G Baroni umberto vespasiani-gentilucci Maria-Gisella Cavallo Sergio Morini Department of Experimental Medicine Sapienza University of Rome Laboratory of Microscopic and Ultrastructural Anatomy(CIR) Faculty of MedicineUniversity Campus Bio-Medico Internal Medicine and Hepatology University Campus Bio-Medico

Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease *** pathogenesis is complex and not yet fully *** the years many studies have proposed various pathophysiological hypotheses,among which the currently most widely accepted is the"multiple parallel hits"*** to this model,lipid accumulation in the hepatocytes and insulin resistance increase the vulnerability of the liver to many factors that act in a coordinated and cooperative manner to promote hepatic injury,inflammation and *** these factors,adipose tissue dysfunction and subsequent chronic low grade inflammation play a crucial *** studies have shown that vitamin D exerts an immune-regulating action on adipose tissue,and the growing wealth of epidemiological data is demonstrating that hypovitaminosis D is associated with both obesity and ***,given the strong association between these conditions,current findings suggest that vitamin D may be involved in the relationship between adipose tissue dysfunction and *** purpose of this review is to provide an overview of recent advances in the pathogenesis of NAFLD in relation to adipose tissue dysfunction,and in the pathophysiology linking vitamin D deficiency with NAFLD and adiposity,together with an overview of the evidence available on the clinical utility of vitamin D supplementation in cases of NAFLD.

关键词： Adipose tissue dysfunction Vitamin D Non-alcoholic fatty liver disease Steatosis Non-alcoholic steatohepatitis Obesity Adipokines

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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

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Proton pump inhibitor prescription abuse and sepsis in cirrhosis

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2016年第1期7卷 1-4页

作者： Antonio Picardi umberto vespasiani-gentilucci Internal Medicine and Hepatology Unit University Campus Bio-Medico

Proton pump inhibitors(PPIs) represent one of the most extensively prescribed classes of drugs in general and in patients with liver cirrhosis. Many prescriptions are made without a clear adherence to standard indications. As a class of ordinarily well tolerated drug, PPIs are not free of side-effects and concerns have been raised about a possible role for PPIs in predisposing patients to an increased risk of bacterial infections and sepsis. As evidences of different power are accumulating on this topic, prospective studies are needed to reach a more universal agreement, but definitely more attention is needed by prescribers in being more adherent to the few recognized indications for the use of PPIs, particularly in patients with liver cirrhosis. Otherwise, doctors could run the risk of being accused of "abused" prescription.

关键词： Proton pump inhibitors Liver cirrhosis Bacterial infection Sepsis

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Hepatitis C and double-hit B cell lymphoma successfully treated by antiviral therapy

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World Journal of Hepatology 2016年第29期8卷 1244-1250页

作者： Giovanni Galati Lorenzo Rampa umberto vespasiani-gentilucci Mirella Marino Francesco Pisani Carlo Cota Alessandro Guidi Antonio Picardi Unit of Internal Medicine and Hepatology Department of Medicine Università Campus Bio-Medico di Roma Department of Pathology Regina Elena National Cancer Institute Hematology and Stem Cell Transplant Unit Regina Elena National Cancer Institute Dermopahology Unit San Gallicano Dermatological Institute IRCCS

B cells lymphoma is one of the most challenging extrahepatic manifestations of hepatitis C virus(HCV). Recently, a new kind of B-cell lymphoma, named doublehit B(DHL), was characterized with an aggressive clinical course whereas a potential association with HCV was not investigated. The new antiviral direct agents(DAAs) against HCV are effective and curative in the majority of HCV infections. We report the first case, to our knowledge, of DHL and HCV-infection successfully treated by new DAAs. According to our experience, a DHL must be suspected in case of HCV-related lymphoma, and an early diagnosis could direct towards a different hematological management because a worse prognosis might be expected. A possible effect of DAAs on DHL regression should be investigated, but eradicating HCV would avoid life-threatening reactivation of viral hepatitis during pharmacological immunosuppression in oncohaematological diseases.

关键词： Hepatitis C Lymphoma Direct antiviral agents Double hit lymphoma Chronic hepatitis C

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Starring role of toll-like receptor-4 activation in the gutliver axis

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World Journal of Gastrointestinal Pathophysiology 2015年第4期6卷 99-109页

作者： Simone Carotti Michele Pier Luca Guarino umberto vespasiani-gentilucci Sergio Morini Laboratory of Microscopic and Ultrastructural Anatomy School of MedicineUniversity Campus Bio-Medico of Rome Gastroenterology Unit School of Medicine University Campus Bio-Medico of Rome Clinical Medicine and Hepatology Unit School of Medicine University Campus Bio-Medico of Rome

Since the introduction of the term "gut-liver axis", many studies have focused on the functional links of intestinal microbiota, barrier function and immune responses to liver physiology. Intestinal and extra-intestinal diseases alter microbiota composition and lead to dysbiosis, which aggravates impaired intestinal barrier function via increased lipopolysaccharide translocation. The subsequent increased passage of gut-derived product from the intestinal lumen to the organ wall and bloodstream affects gut motility and liver biology. The activation of the toll-like receptor 4(TLR-4) likely plays a key role in both cases. This review analyzed the most recent literature on the gut-liver axis, with a particular focus on the role of TLR-4 activation. Findings that linked liver disease with dysbiosis are evaluated, and links between dysbiosis and alterations of intestinal permeability and motility are discussed. We also examine the mechanisms of translocated gut bacteria and/or the bacterial product activation of liver inflammation and fibrogenesis via activity on different hepatic cell types.

关键词： Gut microbiota Dysbiosis Toll-like receptor 4 Gut

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