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Risk stratification of HCC occurrence after HCV eradication:a complicate plot of risk factors related and unrelated to the previous viral disease

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Hepatobiliary Surgery and Nutrition 2020年第4期9卷 511-513页

作者： Valentina Cossiga maria guarino Filomena Morisco Nicola Caporaso Gastroenterology Unit Department of Clinical Medicine and SurgeryUniversity of Naples“Federico II”NaplesItaly

Hepatocellular carcinoma(HCC)is the fifth most common cancer and the second most frequent cause of cancer-related death *** C virus(HCV)infection is one of leading cause of cirrhosis,that is the strongest risk factor ... 详细信息

关键词： cancer death cirrhosis

Direct-acting antivirals and hepatocellular carcinoma in chronic hepatitis C: A few lights and many shadows

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World Journal of Gastroenterology 2018年第24期24卷 2582-2595页

作者： maria guarino Anna Sessa Valentina Cossiga Federica Morando Nicola Caporaso Filomena Morisco Gastroenterology Unit Department of Clinical Medicine and SurgeryUniversity of Naples Federico Ⅱ

With the introduction of direct-acting antiviral agents(DAA), the rate of sustained virological response(SVR) in the treatment of hepatitis C virus(HCV) has radically improved to over 95%. Robust scientific evidence supports a beneficial role of SVR after interferon therapy in the progression of cirrhosis, resulting in a decreased incidence of hepatocellular carcinoma(HCC). However, a debate on the impact of DAAs on the development of HCC is ongoing. This review aimed to analyse the scientific literature regarding the risk of HCC in terms of its recurrence and occurrence after the use of DAAs to eradicate HCV infection. Among 11 studies examining HCC occurrence, the de novo incidence rate ranged from 0 to 7.4%(maximum follow-up: 18 mo). Among 18 studies regarding HCC recurrence, the rate ranged from 0 to 54.4%(maximum "not well-defined" followup: 32 mo). This review highlights the major difficulties in interpreting data and reconciling the results of the included studies. These difficulties include heterogeneous cohorts, potential misclassifications of HCC prior to DAA therapy, the absence of an adequate control group, short follow-up times and different kinds of follow-up. Moreover, no clinical feature-based scoring system accounts for the molecular characteristics and pathobiology of the tumours. Nonetheless, this review does not suggest that there is a higher rate of de novo HCC occurrence or recurrence after DAA therapy in patients with previous HCV infection.

关键词： hepatocellular carcinoma hepatitis C virus direct-acting antiviral agents occurrence recurrence

Hepatitis B and C virus reactivation in immunosuppressed patients with inflammatory bowel disease

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World Journal of Gastroenterology 2014年第13期20卷 3516-3524页

作者： Stefano Sansone maria guarino Fabiana Castiglione Antonio Rispo Francesco Auriemma Ilaria Loperto Matilde Rea Nicola Caporaso Filomena Morisco Gastroenterology Unit Department of Clinical Medicine and SurgeryUniversity of Naples "Federico II"80131 NaplesItaly

In recent years,a number of case reports and clinical studies have highlighted the risk of hepatitis B and C virus reactivation in patients with inflammatory bowel disease who are treated with immunosuppressive *** cases of viral hepatitis reactivation that have been reported are characterized by a wide range of clinical manifestations,from viremia without clinically relevant manifestations to fulminant life-threatening *** development and dissemination of biological immunosuppressive drugs have led to a significant increase in the number of reports of interest to physicians in a variety of clinical *** this topic,there have been a number of published guidelines and reviews that have collected the available evidence,providing recommendations on prophylactic and therapeutic strategies and methods for monitoring patients at ***,it should be noted that,to date,very few clinical studies have been published,and most of the recommendations have been borrowed from otherclinical *** published studies are mostly retrospective and are based on very heterogeneous populations,using different therapeutic and prophylactic regimens and obtaining conflicting ***,it seems clear that it is desirable to concentrate our efforts on prospective studies,not conducting further reviews of the literature in the continued absence of new evidence.

关键词： Inflammatory bowel disease Biological agents Hepatitis B virus reactivation Hepatitis C virus reactivation Prophylaxis

Recurrent ischemic strokes in a young celiac woman with MTHFR gene mutation

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World Journal of Gastroenterology 2012年第26期18卷 3472-3476页

作者： Elisa Fabbri Lisa Rustignoli Antonio Muscari Giovanni M Puddu maria guarino Rita Rinaldi Elena Minguzzi Giacomo Caio Marco Zoli Umberto Volta Stroke Unit Department of Internal MedicineAging and Nephrological DiseasesUniversity of Bologna40138 BolognaItaly Neurology Unit Department of Internal MedicineAging and Nephrological DiseasesS.Orsola-Malpighi Hospital40138 BolognaItaly Department of Digestive Diseases and Internal Medicine S.Orsola-Malpighi Hospital40138 BolognaItaly

Celiac disease(CD) is frequently associated with neurological disorders,but very few reports concern the association with ischemic stroke.A 26-year-old woman affected by CD with secondary amenorrhea,carrier of a homozygous 5,10-methylenetetrahydrofolate reductase mutation with hyperhomocysteinemia,was affected by two occipital ischemic strokes within a period of 5 *** the time of the second stroke,while she was being treated with folic acid,acetylsalicylic acid and a gluten-free diet,she had left hemianopsia,left hemiparesthesias,and gait *** magnetic resonance imaging showed a subacute right occipital ischemic lesion,which was extended to the dorsal region of the right thalamus and the ipsilateral thalamocapsular *** and deamidated gliadin peptide antibodies were no longer present,while antinuclear antibodies,antineuronal antibodies and immune circulating complexes were only slightly *** the patient was taking folic acid,her homocysteine levels were almost normal and apparently not sufficient alone to explain the clinical event.A conventional cerebral angiography showed no signs of ***,rare causes of occipital stroke in young patients,such as Fabry's disease and mitochondrial myopathy,encephalomyopathy,lactic acidosis and stroke-like symptoms,were also excluded by appropriate ***,the most probable cause for the recurrent strokes in this young woman remained CD,although the mechanisms involved are still *** two main hypotheses concern malabsorption(with consequent deficiency of vitamins known to exert neurotrophic and neuroprotective effects) and immunemediated *** should be kept in mind in the differential diagnosis of ischemic stroke in young patients.

关键词： Celiac disease Female Methylenetetrahy-drofolate reductase Stroke Vasculitis Young

Development of a warning score for early detection of colorectal anastomotic leakage:Hype or hope?

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World Journal of Gastrointestinal Surgery 2022年第11期14卷 1297-1309页

作者： Nuno J G Rama Óscar Lourenço Patrícia C Motta Lima maria Pedro S guarino Diana Parente Ricardo Castro Ana Bento Anabela Rocha Fernando Castro-Poças João Pimentel Division of Colorectal Surgical Leiria Hospital CentreLeiria 2410-021Portugal Abel Salazar Biomedical Institute University of OportoOporto 4099-002Portugal Center for Innovative Care and Health Technology(ciTechCare) Polytechnic of LeiriaLeiria 2410-541Portugal Faculty of Economics CeBERUniversity of CoimbraCoimbra 3000-137Portugal Division of Clinical Pathology Leiria Hospital CentreLeiria 2410-541Portugal Division of Surgical Oporto Hospital CentreOporto 4099-001Portugal Department of Gastroenterology Santo António HospitalPorto Hospital CenterOporto 4099-001Portugal Institute of Biomedical Sciences Abel Salazar University of OPortoOporto 4099-001Portugal Faculty of Medicine University of CoimbraCoimbra 3004-531Portugal Division of Surgical Montes Claros HospitalCoimbra 3030-320Portugal

BACKGROUND Colorectal anastomotic leakage(CAL),a severe postoperative complication,is associated with high morbidity,hospital readmission,and overall healthcare *** detection of CAL remains a challenge in clinical ***,some decision models have been developed to increase the diagnostic accuracy of this *** To develop a score based on easily accessible variables to detect CAL *** Based on the least absolute shrinkage and selection operator method,a predictive classification system was developed[Early ColoRectAL Leakage(E-CRALL)score]from a prospective observational,single center cohort,carried out in a colorectal division from a non-academic *** score performance and CAL threshold from postoperative day(POD)3 to POD5 were *** on a precise analytical decision model,the standard clinical practice was compared with the E-CRALL adoption on POD3,POD4,or POD5.A cost-minimization analysis was conducted,on the assumption that all alternatives delivered similar health-related *** In this study,396 patients who underwent colorectal resection surgery with anastomosis,and 6.3%(n=25)developed *** of the patients who developed CAL(n=23;92%)were diagnosed during the first hospital admission,with a median time of diagnosis of 9.0±6.8 *** POD3 to POD5,the area under the receiver operating characteristic curve of the E-CRALL score was 0.82,0.84,and 0.95,*** POD5,if a threshold of 8.29 was chosen,87.4%of anastomotic failures were identified with E-CRALL ***,score usage could anticipate CAL diagnosis in an average of 5.2 d and 4.1 d,if used on POD3 and POD5,*** of score adoption,episode comprehensive costs were markedly greater(up to four times)in patients who developed CAL in comparison with patients who did not develop ***,the use of the E-CRALL warning score was associated with cost savings of€421442.20,with most(92.9%)of the savings from patients

关键词： Anastomotic leakage Colorectal Surgery Biomarkers Score Costs

Usefulness of serum C-reactive protein and calprotectin for the early detection of colorectal anastomotic leakage:A prospective observational study

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World Journal of Gastroenterology 2022年第24期28卷 2758-2774页

作者： Nuno J G Rama Marlene C C Lages maria Pedro S guarino Óscar Lourenço Patrícia C Motta Lima Diana Parente Cândida S G Silva Ricardo Castro Ana Bento Anabela Rocha Fernando Castro-Pocas João Pimente Colorectal Surgical Division Leiria Hospital CentreLeiria 2410-021Portugal Abel Salazar Biomedical Institute(ICBAS) University of OportoOporto 4099-002Portugal Center for Innovative Care and Health Technology(ciTechCare) Polytechnic of LeiriaLeiria 2410-541Portugal Faculty of Economics CeBERUniversity of CoimbraCoimbra 3000-137Portugal Clinical Pathology Division Leiria Hospital CentreLeiria 2410-541Portugal Surgical Division Oporto Hospital CentreOporto 4099-001Portugal Department of Gastroenterology Santo António HospitalPorto Hospital CenterPorto 4099-001Portugal Institute of Biomedical Sciences Abel Salazar University of PortoPorto 4099-001Portugal Faculty of Medicine University of CoimbraCoimbra 3004-531Portugal Surgical Division Montes Claros HospitalCoimbra 3030-320Portugal

BACKGROUND Colorectal anastomotic leakage(CAL)is one of the most dreaded complications after colorectal surgery,with an incidence that can be as high as 27%.This event is associated with increased morbidity and mortality;therefore,its early diagnosis is crucial to reduce clinical consequences and *** biomarkers have been suggested as laboratory tools for the diagnosis of *** To assess the usefulness of plasma C-reactive protein(CRP)and calprotectin(CLP)as early predictors of *** A prospective monocentric observational study was conducted including patients who underwent colorectal resection with anastomosis,from March 2017 to August *** were divided into three groups:G1–no complications;G2–complications not related to CAL;and G3–*** biomarkers were measured and analyzed in the first 5 postoperative days(PODs),namely white blood cell(WBC)count,eosinophil cell count(ECC),CRP,CLP,and procalcitonin(PCT).Clinical criteria,such as abdominal pain and clinical condition,were also *** correlation between biomarkers and CAL was *** operating characteristic(ROC)curve analysis was used to compare the accuracy of these biomarkers as predictors of CAL,and the area under the ROC curve(AUROC),specificity,sensitivity,positive predictive value,and negative predictive value(NPV)during this period were *** In total,25 of 396 patients developed CAL(6.3%),and the mean time for this diagnosis was 9.0±6.8 *** operative characteristics,such as surgical approach,blood loss,intraoperative complications,and duration of the procedure,were notably related to the development of *** length of hospital stay was markedly higher in the group that developed CAL compared with the group with complications other than CAL and the group with no complications(median of 21 d vs 13 d and 7 d respectively;P<0.001).For abdominal pain,the best predictive performance was on POD4 and POD5,with the largest AUROC of 0.84 on ***

关键词： Anastomotic leakage Colorectal Surgery Biomarkers C-reactive protein Calprotectin

Sustained virological response: A milestone in the treatment of chronic hepatitis C

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World Journal of Gastroenterology 2013年第18期19卷 2793-2798页

作者： Filomena Morisco Rocco Granata Tommaso Stroffolini maria guarino Laura Donnarumma Laura Gaeta Ilaria Loperto Ivan Gentile Francesco Auriemma Nicola Caporaso Dipartimento di Medicina Clinica e Chirurgia Gastroenterology Unit University of Naples "Federico Ⅱ" 80131 Naples Italy Dipartimento di Malattie Infettive e Tropicali University of Rome "La Sapienza" 00161 Rome Italy Dipartimento di Medicina Clinica e Chirurgia Infectious Diseases Unit University of Naples "Federico Ⅱ" 80131 Naples Italy

AIM: To evaluate the long-term eradication of hepatitis C virus (HCV) infection and liver-related complications in chronically infected patients that have achieved sustained virological response. METHODS: One hundred and fifty subjects with chronic hepatitis C (CHC) or cirrhosis and sustained virological response (SVR) between the years of 1989 and 2008 were enrolled in a long-term clinical follow-up study at the Gastrointestinal and Liver Unit of the University Hospital of Naples "Federico Ⅱ". At the beginning of the study, the diagnosis of HCV infection was made on the basis of serum positivity for antibodies to HCV and detection of HCV RNA transcripts, while a diagnosis of chronic hepatitis was formulated using imaging techniques and/or a liver biopsy. SVR was achieved by interferon-based therapy, both conventional and pegylated, with and without ribavirin treatment. The patients were evaluated for follow-up at a median length of 8.6 years, but ranged from 2-19.9 years. Among them, 137 patients had pre-treatment CHC and 13 had cirrhosis. The patients were followed with clinical, biochemical, virological, and ultrasound assessments on a given schedule. Finally, a group of 27 patients underwent a liver biopsy at the beginning of the study and transient elastography at their final visit to evaluate changes in liver fibrosis. RESULTS: The median follow-up was 8.6 years (range 2-19.9 years). HCV RNA remained undetectable in all patients, even in patients who eventually developed liver-related complications, indicating no risk of HCV recurrence. Three liver-related complications were observed: two cases of hepatocellular carcinoma and one case of bleeding from esophageal varices resulting in an incidence rate of 0.23%/person per year. Further, all three complications took place in patients diagnosed with cirrhosis before treatment began. Only one death due to liver-related causes occurred, resulting in a mortality rate of 0.077% person per year. This amounts to a 99.33

关键词： Antiviral therapy Cirrhosis Hepatitis C virus Sustained virological response Fibrosis

Polymorphism AGT2(rs4762)is involved in the development of dermatologic events:Proof-of-concept in hepatocellular carcinoma patients treated with sorafenib

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World Journal of Hepatology 2022年第7期14卷 1438-1458页

作者： Víctor Sapena Massimo Iavarone Loreto Boix Floriana Facchetti maria guarino Marco Sanduzzi Zamparelli Alessandro Granito Esther Samper Mario Scartozzi Josep Corominas Giorgia Marisi Alba Díaz Andrea Casadei-Gardini Laura Gramantieri Pietro Lampertico Filomena Morisco Ferran Torres Jordi Bruix María Reig Barcelona Clinic Liver Cancer Group Liver UnitHospital Clínic de BarcelonaInstitut d'Investigacions Biomèdiques August Pi SunyerCentro de Investigación Biomédica en Red Enfermedades Hepáticas y DigestivasBarcelona 08036Spain Universidad de Barcelona Barcelona 08036Spain Division of Gastroenterology and Hepatology Foundation Istituto di Ricovero e Cura a Carattere Scientifico di Natura Pubblica Ca’Granda Ospedale Maggiore PoliclinicoMilano 20122Italy Department of Clinical Medicine and Surgery Gastroenterology UnitUniversity of Naples Federico IINaples 80131Italy Gastroenterology and Hepatology Unit Fondazione Istituto di Ricovero e Cura a Carattere Scientifico di Natura Pubblica CàGranda Ospedale Maggiore PoliclinicoUniversity of MilanMilan 20100Italy Department of Clinical Medicine and Surgery Gastroenterology UnitUniversity of Naples"Federico II"Napoli 80100Italy Department of Clinical Medicine and Surgery Gastroenterology and HepatologyFederico II University of NaplesNaples 80131Italy Division of Internal Medicine Hepatobiliary and Immunoallergic DiseasesIstituto di Ricovero e Cura a Carattere Scientifico di Natura Pubblica Azienda Ospedaliero-Universitaria di BolognaBologna 40139Italy Department of Medical and Surgical Sciences University of BolognaBologna 40139Italy Department of Medical Oncology University of CagliariCagliari 45698Italy Biosciences Laboratory Istituto di Ricovero e Cura a Carattere Scientifico di Natura PubblicaIstituto Romagnolo per lo Studio dei Tumori“Dino Amadori”Meldola 47014Italy Department of Pathology Hospital Clínic de BarcelonaUniversitat de BarcelonaBarcelona 08036Spain School of Medicine Vita-Salute San Raffaele UniversityMilan 20132Italy Unit of Oncology UniversitàVita-SaluteIstituto di Ricovero e Cura a Carattere Scientifico di Natura Pubblica-San Raffaele Scientific InstituteMilan 20132Italy Division of Internal Medicine Hepatobiliary and Immunoallergic DiseasesIstituto di Ricovero e Cura a Carattere Scientifico di Natura Pubblica Aziend

BACKGROUND Dermatologic adverse events(DAEs)are associated with a better outcome in patients with hepatocellular carcinoma(HCC)irrespective of the therapeutic agent *** exact mechanisms associated with the development of DAEs are unknown although several studies point to direct toxicity of tyrosine kinase inhibitors(TKIs)to the skin or an immune-mediated reaction triggered by the oncologic *** is the case in other conditions,individual genetic variants may partially explain a higher risk of *** To evaluate the contribution of several gene variants to the risk of developing DAEs in HCC patients treated with *** We first analyzed 27 single-nucleotide polymorphisms(SNPs)from 12 genes selected as potential predictors of adverse event(AE)development in HCC patients treated with sorafenib[Barcelona Clinic Liver Cancer 1(BCLC1)cohort].Three additional cohorts were analyzed for AGT1(rs699)and AGT2(rs4762)polymorphisms-initially identified as predictors of DAEs:BCLC2(n=79),Northern Italy(n=221)and Naples(n=69)cohorts,*** relation between SNPs and DAEs and death were assessed by univariate and multivariate Cox regression models,and presented with hazard ratios and their 95%confidence intervals(95%CI).RESULTS The BCLC1 cohort showed that patients with arterial hypertension(AHT)(HR=1.61;P value=0.007)and/or AGT SNPs had an increased risk of ***,AGT2(rs4762)AA genotype was found to be linked to a statistically significant increased probability of DAEs(HR=5.97;P value=0.0201,AA vs GG)in the Northern Italy cohort by multivariate analysis adjusted for BCLC stage,ECOG-PS,diabetes and *** value of this genetic marker was externally validated in the cohort combining the BCLC1,BCLC2 and Naples cohorts[HR=3.12(95%CI:1.2-8.14),P value=0.0199,AGT2(rs4762)AA vs AG genotype and HR=2.73(95%CI:1.18-6.32)P value=0.0188,AGT2(rs4762)AA vs GG genotype].None of the other gene variants tested were found to be associated with the risk of D

关键词： HCC Early DAE Single-nucleotide polymorphisms AGT1(rs699) AGT2(rs4762),Tyrosine kinase inhibitors

Interplay between metabolic dysfunction-associated fatty liver disease and renal function: An intriguing pediatric perspective

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World Journal of Gastroenterology 2024年第15期30卷 2081-2086页

作者： Michele Nardolillo Fabiola Rescigno Mario Bartiromo Dario Piatto Stefano guarino Pierluigi Marzuillo Emanuele Miraglia del Giudice Anna Di Sessa Department of Woman Child and of General and Specialized SurgeryUniversitàdegli Studi della Campania“Luigi Vanvitelli”Naples 80138Italy

Over recent years,the nomenclature of non-alcoholic fatty liver disease has undergone significant ***,in 2020,an expert consensus panel proposed the term“Metabolic(dysfunction)associated fatty liver disease”(MAFLD)to underscore the close association of fatty liver with metabolic abnormalities,thereby highlighting the cardiometabolic risks(such as metabolic syndrome,type 2 diabetes,insulin resistance,and cardiovascular disease)faced by these patients since *** recently,this term has been further replaced with metabolic associated steatotic liver *** is worth noting that emerging evidence not only supports a close and independent association of MAFLD with chronic kidney disease in adults but also indicates its interplay with metabolic ***,comparable pediatric data remain *** the progressive and chronic nature of both diseases and their prognostic cardiometabolic implications,this editorial aims to provide a pediatric perspective on the intriguing relationship between MAFLD and renal function in childhood.

关键词： Metabolic(dysfunction)associated fatty liver disease Renal Function Children Obesity