0000000000160346
AUTHOR
Fabrizio Bronte
showing 45 related works from this author
IL28B polymorphisms influence stage of fibrosis and spontaneous or interferon-induced viral clearance in thalassemia patients with hepatitis C virus …
2012
Background. Polymorphisms in the interleukin-28B are important determinants in the spontaneous and drug-induced control of hepatitis C virus infection. Design and Methods. We assessed the association of rs8099917 and rs12979860 polymorphisms with spontaneous viral clearance, severity of liver fibrosis, and response to interferon-monotherapy in 245 Thalassemia Major patients with Hepatitis C Virus infection. Results. Ninety-eight patients (40%) had a spontaneous viral clearance, while 147 patients (60%) developed a chronic infection. Spontaneous viral clearance was more frequent among patients with the T/T genotype of rs8099917 polymorphism (OR 2.130; p=0.008) or C/C genotype of rs12979860 p…
Retreatment with pegylated interferon plus ribavirin of chronic hepatitis C non-responders to interferon plus ribavirin: A meta-analysis.
2009
BACKGROUND/AIMS: Efficacy of retreatment with pegylated interferon (PEG-IFN) plus ribavirin of non-responders to standard or pegylated IFN plus ribavirin has been assessed in various studies, but sustained virologic response (SVR) rates are variable and factors influencing efficacy and tolerability still remain incompletely defined. We aimed to focus on SVR rates and to identify factors influencing them in this meta-analysis. METHODS: MEDLINE as well as a manual search were used. Studies were included if they were controlled or uncontrolled trials, if they had been published as full-length papers and if they included non-responders to standard or pegylated IFN and ribavirin therapy. Fourtee…
Point‐of‐care HCV RNA testing in the setting of DAA therapy: HCV‐FiS (HEpatitis C Virus Fingerstick Study)
2019
HCV-RNA assessment during therapy with Direct-Acting Antiviral (DAA) regimens still relies on assays requiring blood collection and transport to a specialised laboratory, which may compromise linkage to care. GeneXpert-HCV Viral Load (GXHVL) (Cepheid) is a plasma-based assay used at point of care (POC) with a sensitivity of ≤10 IU/mL, and, results available within 2 hours. Fifty-nine consecutive HCV-patients ready for DAAs treatment were enrolled. HCV-RNA was simultaneously tested using Roche TaqMan RT-PCR (venous blood sample) and GXHVL (capillary blood collected by fingerstick), at baseline (BL), week 4 (W4) of therapy, end of therapy (EOT) and week 12 of follow-up (W12FU). Both assays de…
Transient elastography (TE) as a tool to evaluate acute liver damage: A prospective, multicentric cohort study
2008
An Outbreak of Hepatitis C Virus Infection Among Transfused Thalassemia Patients: Root Cause Analysis, Phylogenetic Epidemiology and Antiviral Therapy
2021
Background: Occurrence of HCV infection is reduced by effective risk management procedures, but patient-to-patient transmission continues to be reported in healthcare settings. We report an outbreak of 11 patients with HCV acute hepatitis (seven new infections and four re-infections) among 128 thalassemia patients followed at a Hospital in Sicily. Methods All patients with acute hepatitis and known chronic infection were tested for HCV-RNA, HCV genotyping, and NS3, NS5A and NS5B HCV-genomic regions sequencing. To identify transmission clusters we built phylogenetic trees for each gene employing Bayesian methods. Findings All patients with acute hepatitis were infected with HCV genotype 1b…
Liver disease in chelated transfusion-dependent thalassemics: the role of iron overload and chronic hepatitis C.
2008
Iron overload and hepatitis virus C infection cause liver fibrosis in thalassemics. In a monocentric retrospective analysis of liver disease in a cohort of 191 transfusion-dependent thalassemics, in 126 patients who had undergone liver biopsy (mean age 17.2 years; 58 hepatitis virus C-RNA positive and 68 hepatitis virus C-RNA negative) the liver iron concentration (median 2.4 mg/gr dry liver weight) was closely related to serum ferritin levels (R = 0.58; p<0.0001). Male gender (OR 4.12) and serum hepatitis virus C-RNA positivity (OR 11.04) were independent risk factors for advanced liver fibrosis. The majority of hepatitis virus C-RNA negative patients with low iron load did not develop liv…
HepatomiRNoma: The proposal of a new network of targets for diagnosis, prognosis and therapy in hepatocellular carcinoma
2015
Abstract: The diagnosis and treatment of hepatocellular carcinoma (HCC) underwent a huge advancement in the last years. Recently, microRNAs (miRNAs) have been also studied to provide a new tool for early diagnosis of high risk patients, for prognostic classification to identify those patients who benefit cancer treatment and for predictive definition to select the right targeted drug. In this review we revised all the available data obtained to explore the role of miRNAs in HCC. This analysis led to identification of miRNAs which could gain a diagnostic, prognostic or predictive role. The results of studies on miRNAs involved in HCC are initial and far from providing scientific evidences to…
HBV reactivation in patients with HCV/HBV cirrhosis on treatment with direct-acting antivirals
2017
Anecdotal reports suggest that patients with chronic hepatitis C virus (HCV) hepatitis and overt or occult hepatitis B virus (HBV) coinfection may reactivate HBV when HCV is suppressed or cleared by direct-acting antivirals (DAAs). We assessed the prevalence of overt or previous HBV coinfection and the risk of HBV reactivation in patients with HCV cirrhosis treated with DAAs. This was a retrospective cohort of 104 consecutive patients with HCV cirrhosis treated with DAAs. Serum HCV-RNA and HBV-DNA were tested at weeks 4, 8 and 12 of DAAs therapy and at week 12 of follow-up. At the start of DAAs, eight patients (7.7%) were HBsAg positive/HBeAg negative with undetectable HBV-DNA and low level…
Liver stiffness measurement by transient elastography predicts early recovery from acute hepatitis
2010
We read with interest the lead article by Castera and Pinzani,1 particularly the comment regarding the role of transient elastography (TE) in the context of acute hepatitis (AH). The assumption that liver stiffness is determined exclusively by hepatic fibrosis has been challenged by evidence that patients with AH can have high values of liver stiffness measurement (LSM) by TE.2 AH is a suitable model for studying the kinetics of LSM, since inflammation and necrosis increase rapidly and sometimes massively, but may revert with equal speed. We evaluated 92 consecutive patients (mean age 41.8±16.3 years, 71.7% males) with symptomatic AH to assess how LSM was influenced by aetiology, and whethe…
Insulin resistance is a major determinant of liver stiffness in nondiabetic patients with HCV genotype 1 chronic hepatitis.
2009
BACKGROUND: In patients with chronic hepatitis C (CHC), liver stiffness measurement (LSM) by transient elastography (TE), is closely related to the stage of fibrosis, but may be affected by necroinflammation. Other factors, such as insulin resistance (IR), might influence the performance of LSM. AIMS: To evaluate in a cohort of nondiabetic patients with genotype 1 CHC, whether IR and other anthropometric, biochemical, metabolic and histological factors contribute to LSM and to identify the best cut-off values of LSM for predicting different stages of fibrosis. METHODS: Nondiabetic patients with genotype 1 CHC (n = 156) were evaluated by liver biopsy (Metavir score), anthropometric, biochemi…
Noninvasive assessment of liver fibrosis in thalassaemia major patients by transient elastography (TE) - lack of interference by iron deposition.
2009
The correlation between liver stiffness, measured by transient elastography, liver fibrosis, using the histological METAVIR score, and iron overload, measured by atomic absorption spectrometry was evaluated in 56 homozygous-beta-thalassaemics. Liver stiffness increased proportionally to liver fibrosis staging (r = 0.70; P > 0.001) independently of liver iron concentration (r = 0.01; P = 0.932). The area under the receiver-operating characteristic curve for prediction of cirrhosis was 0.997 (95% confidence interval [CI]: 0.925-1.000) with cut-off of 13 kPa with 100% sensitivity (95% CI: 69.0-100.0) and 95% specificity (95% CI: 84.2-99.3). Transient elastography is a reliable non-invasive too…
Entecavir effectiveness in naïve and NUC experienced patients: Interim analysis of the ENTAS cohort study of patients with chronic hepatitis B
2014
Is Transient Elastography Needed for Noninvasive Assessment of High-Risk Varices? The REAL Experience
2019
INTRODUCTION: The Baveno VI consensus guidelines and an expanded algorithm suggest that transient elastography (TE) and platelet (PLT) count can be used to identify patients with cirrhosis who can avoid esophagogastroduodenoscopy (EGD). The primary aims of this study were to assess the ability of a simple algorithm, which uses only laboratory parameters, to predict medium/large esophageal varices (EV) in patients with hepatitis C virus (HCV) and cirrhosis from the Rete Sicilia Selezione Terapia-HCV (RESIST-HCV) cohort and to compare the performance of the algorithm with Baveno VI and Expanded Baveno VI criteria. The secondary aim was to assess the role of TE in ruling out large EV. METHODS:…
Cardiotoxicity mechanisms of the combination of BRAF-inhibitors and MEK-inhibitors.
2018
Many new drugs have appeared in last years in the oncological treatment scenario. Each drug carries an important set of adverse events, not less, cardiovascular adverse events. This aspect is even more important considering the increasing use of combination therapies with two drugs, or three drugs as in some ongoing clinical trials. Besides it represents a growing problem for Cardiologists, that face it in every day clinical practice and that will face it probably more and more in the coming years. This work reviews the mechanism of action of BRAF-inhibitors and MEK-inhibitors used together, the pathophysiological mechanisms that lead to cardiovascular toxicity. Particularly, it focuses on …
Noninvasive assessment of liver fibrosis in thalassaemia major patients by transient elastography (TE) - lack of interference by iron deposition.
2009
The correlation between liver stiffness, measured by transient elastography, liver fibrosis, using the histological METAVIR score, and iron overload, measured by atomic absorption spectrometry was evaluated in 56 homozygous-b-thalassaemics. Liver stiffness increased proportionally to liver fibrosis staging (r = 0Æ70; P > 0Æ001) independently of liver iron concentration (r = 0Æ01; P = 0Æ932). The area under the receiver-operating characteristic curve for prediction of cirrhosis was 0Æ997 (95% confidence interval [CI]: 0Æ925–1Æ000) with cut-off of 13 kPa with 100% sensitivity (95% CI: 69Æ0–100Æ0) and 95% specificity (95% CI: 84Æ2–99Æ3). Transient elastography is a reliable non-invasive tool f…
Targeted Therapies in Hepatocellular Carcinoma
2015
Hepatocellular carcinoma (HCC) is one of the main causes of death in patients affected by chronic liver diseases. The awareness of the biomolecular mechanisms underlying the complex carcinogenic process led to the development of targeted molecules, which are able to block this process. Sorafenib is a tyrosine-kinase inhibitor, and currently, it is the only drug approved by the US Food and Drug Administration (FDA) for the treatment of HCC. However, some studies have demonstrated the efficacy of single drug therapies or combination therapies. They showed an improvement with regard to overall survival, time to progression, and progression-free survival, although these therapies were not free …
Transient elastography vs. platelets or APRI score to assess fibrosis in chronic hepatitis C
2008
Fibrosis staging in chronic hepatitis C: Analysis of discordance between transient elastography and liver biopsy
2009
Summary. In chronic hepatitis C, transient elastography (TE) accurately identifies cirrhosis, but its ability to assess significant fibrosis (Metavir ≥ F2) is variable. Constitutional and liver disease-related factors may influence TE and here we examined the variables associated with differences. Three hundred consecutive hepatitis C virus (HCV)-RNA positive patients had biochemical tests, TE and a biopsy performed on the same day. The Dale model was used to identify the variables associated with discordance between biopsy and elastography results. In 97 patients (34.2%), TE and histological assessment were discordant. Seventy-six of 286 (26.6%) had stage ≥F2 and TE < 7.1 kPa (false negat…
Comparison of transient elastography and acoustic radiation force impulse for non-invasive staging of liver fibrosis in patients with chronic hepatit…
2011
Transient elastography (TE) is adequate for a diagnosis of cirrhosis, but its accuracy for milder stages of fibrosis is much less satisfactory. The objective of this study was to compare the performance and the discordance rate of acoustic radiation force impulse (ARFI) and TE with liver biopsy in a cohort of chronic hepatitis C (CHC) patients.One hundred thirty-nine consecutive patients with CHC were enrolled in two tertiary centers, and evaluated for histological (Metavir score) and biochemical features. All patients underwent TE and ARFI.TE was unreliable in nine patients (6.5%), while in no cases (0%) were ARFI invalid measurements recorded (P=0.029). By area under receiver operating ch…
What links BRAF to the heart function? new insights from the cardiotoxicity of BRAF inhibitors in cancer treatment
2015
The RAS-related signalling cascade has a fundamental role in cell. It activates differentiation and survival. It is particularly important one of its molecules, B-RAF. B-RAF has been a central point for research, especially in melanoma. Indeed, it lacked effective therapeutic weapons since the early years of its study. Molecules targeting B-RAF have been developed. Nowadays, two classes of molecules are approved by FDA. Multi-target molecules, such as Sorafenib and Regorafenib, and selective molecules, such as Vemurafenib and Dabrafenib. Many other molecules are still under investigation. Most of them are studied in phase 1 trials. Clinical studies correlate B-RAF inhibitors and QT prolonga…
Modified spleen stiffness measurement by transient elastography is associated with presence of large oesophageal varices in patients with compensated…
2013
To evaluate the accuracy of liver transient elastography (TE), spleen TE and other noninvasive tests (AAR, APRI score, platelet count, platelet/spleen ratio) in predicting the presence and the size of oesophageal varices in compensated hepatitis C virus (HCV) cirrhosis, we studied 112 consecutive patients with compensated HCV cirrhosis who underwent biochemical tests, gastrointestinal endoscopy, liver TE and spleen TE by Fibroscan(®) (Echosens, Paris, France) using a modified software version with a range between 1.5 and 150 kPa. Spleen TE was not reliable in 16 patients (14.3%). Among the 96 patients with a valid measurement (69.8% men, mean age: 63.2 ± 9.5 years), 43.7% had no oesophageal…
Dual therapy with peg-interferon and ribavirin in thalassemia major patients with chronic HCV infection: Is there still an indication?
2016
Background: Iron overload and hepatitis C virus (HCV) infection together can lead to chronic liver damage in thalassemia major (TM) patients. Aims: We investigated viral, genetic, and disease factors influencing sustained virological response (SVR) after peg-interferon and ribavirin therapy in TM patients with HCV infection. Methods: We analyzed 230 TM patients with HCV infection (mean age 36.0 ± 6.3 years; 59.1% genotype 1; 32.2% genotype 2; 3.4% genotype 3; and 5.3% genotype 4; 28.7% carried CC allele of rs12979860 in IL28B locus; 79.6% had chronic hepatitis and 20.4% cirrhosis; 63.5% naive and 36.5% previously treated with interferon alone) treated in 14 Italian centers. Results: By mul…
Refining the Baveno VI elastography criteria for the definition of compensated advanced chronic liver disease
2021
Background: The Baveno VI consensus proposed a dual liver stiffness (LS) by transient elastography threshold of <10 and >15 kPa for excluding and diagnosing compensated advanced chronic liver disease (cACLD) in the absence of other clinical signs. Herein, we aimed to validate these criteria in a real-world multicentre study. Methods: We included 5,648 patients (mean age 51 ± 13 years, 53% males) from 10 European liver centres who had a liver biopsy and LS measurement within 6 months. We included patients with chronic hepatitis C (n = 2,913, 52%), non-alcoholic fatty liver disease (NAFLD, n = 1,073, 19%), alcohol-related liver disease (ALD, n = 946, 17%) or chronic hepatitis B (n = 716…
Error factors for transient elastography in chronic hepatitis C
2008
High rate of misclassification of fibrosis stage using transient elastography thresholds to prioritize HCV patients for antiviral treatment
2017
Targeted Therapies in Hepatocellular Carcinoma
2014
Abstract: The onset of hepatocellular carcinoma (HCC) is related to the development of non-neoplastic liver disease, such as viral infections and cirrhosis. Even though patients with chronic liver diseases undergo clinical surveillance for early diagnosis of HCC, this cancer is often diagnosed in advanced stage. In this case locoregional treatment is not possible and systemic therapies are the best way to control it. Until now sorafenib, a Raf and multi-kinase inhibitor has been the best, choice to treat HCC systemically. It showed a survival benefit in multicenter phase III trials. However the proper patient setting to treat is not well defined, since the results in Child-Pugh B patients a…
The risk of hepatocellular carcinoma in HBV cirrhosis is affected by polymorphisms of the MERTK gene
2014
Quantification of fibrosis by collagen proportionate area predicts hepatic decompensation in hepatitis C cirrhosis.
2015
SummaryBackground It is unclear whether the course of cirrhosis and its prognosis are related to the amount of collagen in the liver. Aim To determine whether fibrosis, assessed by collagen proportionate area (CPA) in patients with compensated cirrhosis, is associated with the presence of oesophageal varices, and predict disease decompensation during the follow-up period. Methods We prospectively evaluated 118 consecutive patients with compensated cirrhosis to correlate fibrosis, assessed by CPA in liver biopsies, with the presence of oesophageal varices (OV) and with the rate of liver decompensation (LD) development during a median follow-up of 72 months. Results At baseline 38 (32.2%) pat…
Insulin resistance is a risk factor for esophageal varices in hepatitis C virus cirrhosis
2008
Indirect methods to predict the presence of esophageal varices (EV) in patients with cirrhosis are not sensitive enough to be used as a surrogate for endoscopy. We tested the effectiveness of liver stiffness measurement (LSM) by transient elastography and the presence of insulin resistance (IR), a marker associated with fibrosis progression, in the noninvasive prediction of portal hypertension. One hundred four consecutive patients with newly diagnosed Child A hepatitis C virus (HCV) cirrhosis underwent upper gastrointestinal endoscopy to search for EV. Clinical, anthropometric, biochemical, ultrasonographic, and metabolic features, including IR by the homeostasis model assessment (HOMA), a…
Naïve hepatitis B e antigen-negative chronic hepatitis B patients are at risk of carotid atherosclerosis: A prospective study
2021
BACKGROUND There is an increased risk of atherosclerosis in patients with chronic hepatitis C or human immunodeficiency virus, but there is scarce data on hepatitis B virus infection. The hypothesis of this study is that hepatitis B virus infection increases the risk of carotid plaques and subclinical atherosclerosis in naïve hepatitis B e antigen (HBeAg) negative subjects. AIM To assess the rate of carotid plaques and subclinical atherosclerosis in naïve HBeAg negative subjects in comparison with a cohort of healthy controls. METHODS Prospective case-control collaborative study conducted in two tertiary hospitals. Four hundred and two subjects prospectively recruited at the outpatient clin…
Phylogenetic analysis in the clinical risk management of an outbreak of hepatitis C virus infection among transfused thalassaemia patients in Italy
2021
Background: Occurrence of hepatitis C virus (HCV) infection is reduced by effective risk management procedures, but patient-to-patient transmission continues to be reported in healthcare settings. Aim: To report the use of phylogenetic analysis in the clinical risk management of an HCV outbreak among 128 thalassaemia outpatients followed at a thalassaemia centre of an Italian hospital. Methods: Epidemiological investigation and root-cause analysis were performed. All patients with acute hepatitis and known chronic infection were tested for HCV RNA, HCV genotyping, and NS3, NS5A, and NS5B HCV genomic region sequencing. To identify transmission clusters, phylogenetic trees were built for each…
Cost-effectiveness of boceprevir or telaprevir for untreated patients with genotype 1 chronic hepatitis C.
2012
BACKGROUND AND AIMS: Randomized controlled trials (RCTs) show that triple therapy (TT) with peginterferon alfa, ribavirin and boceprevir (BOC) or telaprevir (TVR) is more effective than peginterferon-ribavirin dual therapy (DT) in the treatment of previously untreated patients with genotype 1 (G1) chronic hepatitis C (CHC). We assess the cost-effectiveness of TT compared to DT in the treatment of untreated patients with G1 CHC. METHODS: We created a Markov Decision Model to evaluate, in an untreated Caucasian patients aged 50 years, weight 70 kg, with G1 CHC and Metavir F2 liver fibrosis score, for a time horizon of twenty years, the cost-effectiveness of the following 5 competing strategie…
Retreatment with pegylated interferon plus ribavirin of chronic hepatitis C non-responders to interferon plus ribavirin: A meta-analysis
2009
Efficacy of retreatment with pegylated interferon (PEG-IFN) plus ribavirin of non-responders to standard or pegylated IFN plus ribavirin has been assessed in various studies, but sustained virologic response (SVR) rates are variable and factors influencing efficacy and tolerability still remain incompletely defined. We aimed to focus on SVR rates and to identify factors influencing them in this meta-analysis.MEDLINE as well as a manual search were used. Studies were included if they were controlled or uncontrolled trials, if they had been published as full-length papers and if they included non-responders to standard or pegylated IFN and ribavirin therapy. Fourteen trials were included in t…
HBsAg quantification in HBeAg negative cirrhosis on nucleoside/nucleotide analogue (NA) and risk of development of HCC
2013
GENETIC, VIROLOGICAL AND CLINICAL FACTORS ASSOCIATED WITH HEPATOCELLULAR CARCINOMA DEVELOPEMENT IN PATIENTS WITH CHRONIC HBV AND HCV INFECTION
Comparison of Histochemical Stainings in Evaluation of Liver Fibrosis and Correlation with Transient Elastography in Chronic Hepatitis.
2015
Background and Aim. The best staining to evaluate liver fibrosis in liver hepatitis is still a debated topic. This study aimed to compare Masson’s trichrome (MT), Sirius Red (SR), and orcein stainings in evaluating liver fibrosis in chronic HCV hepatitis (CHC) with semiquantitative and quantitative methods (Collagen Proportionate Area (CPA) by Digital Image Analysis (DIA)) and correlate them with transient elastography (TE).Methods. Liver stiffness evaluation of 111 consecutive patients with CHC was performed by TE. Semiquantitative staging by Metavir score system and CPA by DIA were assessed on liver biopsy stained with MT, SR, and orcein.Results. MT, SR, and orcein staining showed concord…
Quantification of fibrosis in chronic hepatitis C: Performance of Transient Elastography and Acoustic Radiation Force Impulse using Collagen Proporti…
2014
Conquests and perspectives of cardio-oncology in the field of tumor angiogenesis-targeting tyrosine kinase inhibitor-based therapy
2015
Abstract: Introduction: Angiogenesis is fundamental for tumor development and progression. Hence, anti-angiogenic drugs have been developed to target VEGF and its receptors (VEGFRs). Several tyrosine kinase inhibitors (TKIs) have been developed over the years and others are still under investigation, each anti-VEGFR TKI showing a different cardiotoxic profile. Knowledge of the cardiac side-effects of each drug and the magnitude of their expression and frequency can lead to a specific approach. Areas covered: This work reviews the mechanism of action of anti-VEGFR TKIs and the pathophysiological mechanisms leading to cardiotoxicity, followed by close examination of the most important drugs i…
Effectiveness and safety of switching to entecavir hepatitis B patients developing kidney dysfunction during tenofovir
2019
Background and Aims: Tenofovir disoproxil fumarate (TDF) is recommended for chronic hepatitis B (CHB) treatment, but it may induce kidney dysfunction whose management is not yet known. This Italian, multicentre, retrospective study aimed to assess the efficacy and safety of switching to entecavir (ETV) patients who developed TDF-associated glomerular and/or tubular dysfunction. Methods: A total of 103 TDF-treated patients were included as follows: age 64 years, 83% male, 49% cirrhotics, 98% with undetectable HBV DNA, 47% with previous lamivudine resistance (LMV-R) and 71% previously treated with adefovir. Twenty-nine (28%) were switched to ETV because estimated glomerular filtration rate (e…
NS5A gene analysis by next generation sequencing in HCV nosocomial transmission clusters of HCV genotype 1b infected patients
2019
Background: The aim of the study was to investigate the intra-host variability through next-generation-sequencing (NGS) of the NS5A-gene in nosocomial transmission-clusters observed in two Italian hospitals among hepatitis C virus (HCV)-genotype-1b infected patients. Methods: HCV-sequencing was performed by Sanger-sequencing (NS3 + NS5A + NS5B) and by NGS (NS5A, MiSeq-Illumina) in 15 HCV-1b infected patients [five acute with onco-hematologic-disease and 10 (4/6 acute/chronic) with &beta