34 results on '"Donatella Ferraro"'
Search Results
2. An Analysis of the Neutralizing Antibodies against the Main SARS-CoV-2 Variants in Healthcare Workers (HCWs) Vaccinated against or Infected by SARS-CoV-2
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Palmira Immordino, Vincenzo Pisciotta, Emanuele Amodio, Celestino Bonura, Floriana Bonura, Federica Cacioppo, Giuseppe Calamusa, Giuseppina Capra, Alessandra Casuccio, Simona De Grazia, Dario Genovese, Davide Graci, Guido Lacca, Giuseppa Luisa Sanfilippo, Maria Gabriella Verso, Giovanni Maurizio Giammanco, and Donatella Ferraro
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SARS-CoV-2 ,healthcare workers ,vaccine ,COVID-19 ,neutralizing antibodies ,variants of concern ,Medicine - Abstract
Although the anti-COVID-19 vaccination has proved to be an effective preventive tool, “breakthrough infections” have been documented in patients with complete primary vaccination courses. Most of the SARS-CoV-2 neutralizing antibodies produced after SARS-CoV-2 infection target the spike protein receptor-binding domain which has an important role in facilitating viral entry and the infection of the host cells. SARS-CoV-2 has demonstrated the ability to evolve by accumulating mutations in the spike protein to escape the humoral response of a host. The aim of this study was to compare the titers of neutralizing antibodies (NtAbs) against the variants of SARS-CoV-2 by analyzing the sera of recovered and vaccinated healthcare workers (HCWs). A total of 293 HCWs were enrolled and divided into three cohorts as follows: 91 who had recovered from SARS-CoV-2 infection (nVP); 102 that were vaccinated and became positive after the primary cycle (VP); and 100 that were vaccinated with complete primary cycles and concluded the follow-up period without becoming positive (VN). Higher neutralization titers were observed in the vaccinated subjects’ arms compared to the nVP subjects’ arms. Differences in neutralization titers between arms for single variants were statistically highly significant (p < 0.001), except for the differences between titers against the Alpha variant in the nVP and in VP groups, which were also statistically significant (p < 0.05). Within the nVP group, the number of subjects with an absence of neutralizing antibodies was high. The presence of higher titers in patients with a complete primary cycle compared to patients who had recovered from infection suggested the better efficacy of artificial immunization compared to natural immunization, and this further encourages the promotion of vaccination even in subjects with previous infections.
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- 2023
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3. Age and Cytokine Gene Variants Modulate the Immunogenicity and Protective Effect of SARS-CoV-2 mRNA-Based Vaccination
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Letizia Scola, Donatella Ferraro, Giuseppa Luisa Sanfilippo, Simona De Grazia, Domenico Lio, and Giovanni Maurizio Giammanco
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anti-SARS-CoV-2 vaccine ,anti-SARS-CoV-2 S1/S2 IgG ,cytokine gene SNPs ,IL-1R1 rs2234650 ,IL-6 rs1800795 ,IL-4 rs2243250 ,Medicine - Abstract
The introduction of anti-SARS-CoV-2 vaccines in late 2020 substantially changed the pandemic picture, inducing effective protection in the population. However, individual variability was observed with different levels of cellular response and neutralizing antibodies. We report data on the impact of age, gender, and 16 single nucleotide polymorphisms (SNPs) of cytokine genes on the anti-SARS-CoV-2 IgG titers measured 31 and 105 days after administration of the second dose of BNT162b2 vaccine to 122 healthy subjects from the health care staff of the Palermo University Hospital, Italy. The higher titers at 31 days were measured in the younger subjects and in subjects bearing T-positive genotypes of IL-1R1 rs2234650 or the GG homozygous genotype of IL-6 rs1800795 SNP. T-positive genotypes are also significantly more common in subjects with higher titers at day 105. In addition, in this group of subjects, the frequency of the CT genotype of IL-4 rs2243250 is higher among those vaccinated with higher titers. Moreover, these SNPs and TNFA rs1800629 are differently distributed in a group of subjects that were found infected by SARS-CoV-2 at day 105 of evaluation. Finally, subjects that were found to be infected by SARS-CoV-2 at day 105 were significantly older than the uninfected subjects. Taken together, these data seem to suggest that age and polymorphisms of key cytokines, which regulate inflammation and humoral immune response, might influence the magnitude of the antibody response to vaccination with BNT162B2, prompting speculation about the possible benefit of a genetic background-based assessment of a personalized approach to the anti-COVID vaccination schedule.
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- 2023
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4. Neutralizing Antibodies Response against SARS-CoV-2 Variants of Concern Elicited by Prior Infection or mRNA BNT162b2 Vaccination
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Floriana Bonura, Dario Genovese, Emanuele Amodio, Giuseppe Calamusa, Giuseppa Luisa Sanfilippo, Federica Cacioppo, Giovanni Maurizio Giammanco, Simona De Grazia, and Donatella Ferraro
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SARS-CoV-2 ,VOC ,Omicron ,Italy ,neutralizing antibody titers ,NtAb ,Medicine - Abstract
In order to determine the humoral protective response against SARS-CoV-2, the vaccine-induced and naturally induced neutralizing antibodies (NtAbs) responses against SARS-CoV-2 variants circulating in Italy through in vitro live virus neutralization assay were evaluated. A total of 39 SARS-CoV-2 recovered subjects (COVID-19+) and 63 subjects with a two-dose cycle of the BNT16262 vaccine were enrolled. A single serum sample was tested for COVID-19+ at 35–52 days post-positive swab, while vaccinees blood samples were taken at one (V1) and at three months (V3) after administration of the second vaccine dose. Significantly higher NtAb titers were found against B.1 and Alpha in both COVID-19+ and vaccinees, while lower NtAb titers were detected against Delta, Gamma, and Omicron variants. A comparison between groups showed that NtAb titers were significantly higher in both V1 and V3 than in COVID-19+, except against the Omicron variant where no significant difference was found. COVID-19+ showed lower neutralizing titers against all viral variants when compared to the vaccinees. Two-dose vaccination induced a sustained antibody response against each analyzed variant, except for Omicron. The evolution process of SARS-CoV-2, through variants originating from an accumulation of mutations, can erode the neutralizing effectiveness of natural and vaccine-elicited immunity. Therefore, a need for new vaccines should be evaluated to contain the ongoing pandemic.
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- 2022
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5. Antibodies Responses to SARS-CoV-2 in a Large Cohort of Vaccinated Subjects and Seropositive Patients
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Emanuele Amodio, Giuseppina Capra, Alessandra Casuccio, Simona De Grazia, Dario Genovese, Stefano Pizzo, Giuseppe Calamusa, Donatella Ferraro, Giovanni Maurizio Giammanco, Francesco Vitale, and Floriana Bonura
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COVID-19 vaccine ,SARS-CoV-2 infection ,antibody concentrations ,Medicine - Abstract
COVID-19 is a current global threat, and the characterization of antibody response is vitally important to update vaccine development and strategies. In this study we assessed SARS-CoV-2 antibody concentrations in SARS-CoV-2 positive patients (N = 272) and subjects vaccinated with the BNT162b2 m-RNA COVID-19 vaccine (N = 1256). For each participant, socio-demographic data, COVID-19 vaccination records, serological analyses, and SARS-CoV-2 infection status were collected. IgG antibodies against S1/S2 antigens of SARS-CoV-2 were detected. Almost all vaccinated subjects (99.8%) showed a seropositivity to anti-SARS-COV-2 IgG and more than 80% of vaccinated subjects had IgG concentrations > 200 AU/mL. In a Tobit multivariable regression analysis, SARS-CoV-2 vaccination was statistically significantly associated with increased IgG concentrations (β coef = 266.4; p < 0.001). A statistically significant reduction in SARS-CoV-2 IgG concentrations was found with older age (β coef = −1.96 per year increase; p < 0.001), male sex (β coef = −22.3; p < 0.001), and days after immunization (β coef = −1.67 per day increase; p < 0.001). Our findings could support the vaccination campaigns confirming the high immunogenicity of the SARS-CoV-2 vaccine under investigation with respect to the natural infection. Further studies will be required for evaluating the role of age and days after immunization in the persistence of vaccine antibodies and protection from the disease.
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- 2021
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6. Phylodynamic Analysis and Implication of HCV Genotype 4 Variability on Antiviral Drug Response and T-Cell Recognition
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Giuseppina Maria Elena Colomba, Noemi Urone, Vito di Marco, and Donatella Ferraro
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phylodynamic ,HCV ,genotype 4 ,DAA ,Bayesian analysis ,viral epitopes ,Microbiology ,QR1-502 - Abstract
Therapies for HCV care could change the prevalence and the geographic distribution of genotypes due to differences in Sustained Virologic Response (SVR). In this scenario, uncommon genotypes/subtypes, such as genotype 4, could spread from high-risk groups, replacing genotypes eradicated by antiviral drugs. Genotype eradication is also strongly influenced by the CD8+ T cell response. In this study, the genetic variability in HCV genotype 4 strains obtained from a cohort of 67 patients naïve to DAA therapy was evaluated. We found that the presence of resistance-associated substitutions (RAS) was able to affect drug responses. Next, using a prediction tool, viral mutations were identified by their ability, or lack thereof, to reduce the binding affinity with HLA, which affects T cell recognition. The Bayesian coalescent analysis suggested two different circulation clusters, one in risk groups (IDUs and MSM) and the other due to migration flows, dated to 1940 and 1915, respectively. Most of the RAS overlapped with HLA and a lack of binding mutations was observed in 96% of strains. This study describes the introduction of HCV genotype 4 in a region of the Mediterranean basin and evaluates how HCV genotype 4’s genetic variability could affect the response of antiviral drugs and CD8+ T cell recognition.
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- 2020
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7. Liver disease in chelated transfusion-dependent thalassemics: the role of iron overload and chronic hepatitis C
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Vito Di Marco, Marcello Capra, Francesco Gagliardotto, Zelia Borsellino, Daniela Cabibi, Francesco Barbaria, Donatella Ferraro, Liana Cuccia, Giovanni Battista Ruffo, Fabrizio Bronte, Rosa Di Stefano, Piero L. Almasio, and Antonio Craxì
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
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
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- 2008
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8. Differing kinetics of anti-spike protein IgGs and neutralizing antibodies against SARS-CoV-2 after Comirnaty (BNT162b2) immunization
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Floriana Bonura, Simona De Grazia, Celestino Bonura, Giuseppa L. Sanfilippo, Giovanni M. Giammanco, Emanuele Amodio, Donatella Ferraro, Bonura, Floriana, De Grazia, Simona, Bonura, Celestino, Sanfilippo, Giuseppa L, Giammanco, Giovanni, Amodio, Emanuele, and Ferraro, Donatella
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Settore MED/07 - Microbiologia E Microbiologia Clinica ,Vaccines, Synthetic ,COVID-19 Vaccines ,SARS-CoV-2 ,Vaccination ,COVID-19 ,General Medicine ,neutralizing antibodies ,Settore MED/42 - Igiene Generale E Applicata ,Antibodies, Viral ,Antibodies, Neutralizing ,Applied Microbiology and Biotechnology ,Kinetics ,Italy ,healthcare worker ,Immunoglobulin G ,Spike Glycoprotein, Coronavirus ,Humans ,mRNA Vaccines ,kinetics of antibodie ,BNT162 Vaccine ,Biotechnology - Abstract
Aims Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has had a serious worldwide impact on human health. On December 2020, an immunization campaign with a COVID-19 mRNA vaccine (Comirnaty-BNT162b2 Pfizer-BioNTech) was started in Italy, first targeting healthcare workers (HCWs). This study aims to investigate the antibodies that are response against SARS-CoV-2 vaccine. Methods and Results The kinetics and the persistence of both anti-S1/S2 IgGs and neutralizing antibodies (Nt-Abs) were investigated in 76 HCWs through a 4-month follow-up with multiple testing points starting at the first dose. Temporal analysis of SARS-CoV-2 Abs titre kinetics showed three different stages, with an initial slow growth in the anti-S1/S2 IgGs and Nt-Abs titres, corresponding to the first 4 weeks after the first dose of vaccine, followed by a second stage with peaks in titres, around 35 days after the first dose, and by a third stage (38 to 90–120 days after the first dose) showing a steady decrease in anti-S1/S2 IgGs while Nt-Abs are maintained at stable levels. Moreover, the levels of specific Nt-Abs to SARS-CoV-2 Spike protein are correlated to the anti-S1/S2 IgG titre (R-squared = 0.47; p < 0.001). Conclusions The levels of specific Nt-Abs to SARS-CoV-2 Spike protein are correlated to the anti-S1/S2 IgG titre, although Nt-Abs could maintain a more stable titre over the time despite declining IgG Abs titre. Significance and Impact This study highlights the kinetics and the persistence of Nt-Abs in HCWs vaccinated with Comirnaty (BNT162b2) Pfizer-BioNTech, and compared the Nt-Abs levels with anti-SARS-CoV-2 S1/S2 IgGs titres during a 4-month follow-up starting at the first dose of vaccine.
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- 2022
9. Efficacy of 8 weeks elbasvir/grazoprevir regimen for naïve-genotype 1b, HCV infected patients with or without glucose abnormalities: Results of the EGG18 study
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Vito Di Marco, Anna Licata, Antonio Craxì, Salvatore Petta, Francesca Ceccherini-Silberstein, Gerlando Gibilaro, Donatella Ferraro, Claudia La Mantia, Velia Chiara Di Maio, Giada Reina, Vincenza Calvaruso, and Vincenza Calvaruso , Salvatore Petta, Donatella Ferraro, Claudia La Mantia, Gerlando Gibilaro, Giada Reina, Velia Chiara Di Maio, Anna Licata, Francesca Ceccherini-Silberstein, Vito Di Marco, Antonio Craxì
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Cyclopropanes ,Male ,medicine.medical_specialty ,Elbasvir ,Genotype ,Hepatitis C virus ,Hepacivirus ,medicine.disease_cause ,Gastroenterology ,Antiviral Agents ,Settore MED/07 ,Insulin resistance ,Fibrosis ,Internal medicine ,Quinoxalines ,Ribavirin ,medicine ,Elbasvir, Grazoprevir ,Humans ,Aged ,Benzofurans ,Sulfonamides ,Hepatology ,business.industry ,Imidazoles ,Hepatitis C ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,Amides ,Sustained virological response ,Regimen ,Glucose ,Grazoprevir ,HCV ,RNA ,Drug Therapy, Combination ,Female ,Carbamates ,Safety ,Liver stiffness ,business - Abstract
Background and aim: Direct Acting Antivirals(DAAs) achieve the highest rate of sustained viral re- sponse(SVR) in patients with genotype-1b(G1b) Hepatitis C virus(HCV) infection. Reducing treatment du- ration can simplify the management and improve adherence of therapy. Patients and methods: The study evaluates the efficacy of 8 weeks of elbasvir/grazoprevir regimen in 75 treatment-naïve(TN), G1b patients with mild-moderate fibrosis(Liver Stiffness by Fibroscan®< 9.0 kPa). Viral load(VL) has been evaluated by Roche TaqMan RT-PCR(LLOQ < 15 IU/ml). Results: Mean age was 61.0 ±14.2 years, 44% were male, mean LS by Fibroscan®was 6.1 ±1.8 kPa. Twenty-eight patients(37.3%) had an HOMA > 2.5. Two patients were excluded from analysis(one dropped out and the other one had diagnosed genotype 2c at genotyping by sequencing performed after relapse). At 8 weeks(EOT), 71 out of 73 patients(97.3%) had undetectable HCV-RNA, while in two cases HCV- RNA was detectable but with VL < 15 IU/ml. Both of them achieved SVR. Two G1b patients relapsed at 12 weeks of follow-up, both with baseline VL > 80 0,0 0 0 IU/ml and HOMA score 1.3 and 3.8 respectively. Both had undetectable HCV VL at 4th week and at the EOT. Modified intention-to-treat SVR12 for G1b patients was 71/73(97.3%). Conclusion: In naïve, genotype-1b HCV-infected patients with mild/moderate liver fibrosis, short course of 8 weeks of EBR/GZR appears to achieve high efficacy regardless of features of insulin resistance.
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- 2021
10. Phylogenetic analysis in the clinical risk management of an outbreak of hepatitis C virus infection among transfused thalassaemia patients in Italy
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Stefania Grimaudo, Francesca Ceccherini-Silberstein, Lavinia Fabeni, V. Di Marco, Marianna Aragri, F. Di Raimondo, Claudia Marotta, Mazzucco W, Fabrizio Bronte, Maurizio Macaluso, Francesco Vitale, V. Chiara di Maio, Donatella Ferraro, Rosaria Maria Pipitone, Mazzucco W., Chiara di Maio V., Bronte F., Fabeni L., Pipitone R.M., Grimaudo S., Ferraro D., Marotta C., Aragri M., Macaluso M., Vitale F., Di Raimondo F., Ceccherini-Silberstein F., and Di Marco V.
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Sofosbuvir ,Clinical risk management, Hepatitis C virus (HCV), Molecular epidemiology, Nosocomial outbreak, Phylogenetic analysis, Antiviral Agents, Bayes Theorem, Disease Outbreaks, Genotype, Hepacivirus, Humans, Italy, Phylogeny, Risk Management, Hepatitis C, Thalassemia ,Hepacivirus ,030501 epidemiology ,Settore MED/42 - Igiene Generale E Applicata ,medicine.disease_cause ,Disease Outbreaks ,Settore MED/07 ,chemistry.chemical_compound ,Settore BIO/13 - Biologia Applicata ,Epidemiology ,Medicine ,Phylogeny ,Settore MED/12 - Gastroenterologia ,0303 health sciences ,Clinical risk management ,Phylogenetic analysis ,biology ,Transmission (medicine) ,virus diseases ,General Medicine ,Hepatitis C ,Hepatitis C virus (HCV) ,Infectious Diseases ,Italy ,Molecular epidemiology ,Thalassemia ,0305 other medical science ,medicine.drug ,Microbiology (medical) ,Ledipasvir ,medicine.medical_specialty ,Genotype ,Hepatitis C virus ,Antiviral Agents ,03 medical and health sciences ,Phylogenetic analysi ,Internal medicine ,Humans ,Risk Management ,030306 microbiology ,business.industry ,Nosocomial outbreak ,Bayes Theorem ,biology.organism_classification ,medicine.disease ,digestive system diseases ,Chronic infection ,chemistry ,business - Abstract
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 gene employing Bayesian methods. Findings: All patients with acute hepatitis were infected with HCV genotype 1b. Root-cause analysis, including a lookback procedure, excluded blood donors as the source of HCV transmission. The phylogenetic analysis, conducted on seven patients with acute infection and eight patients with chronic infection, highlighted four transmission clusters including at least one patient with chronic and one patient with acute HCV infection. All patients in the same cluster received a blood transfusion during the same day. Two patients with acute hepatitis spontaneously cleared HCV within four weeks and nine patients received ledipasvir plus sofosbuvir for six weeks, all achieving a sustained virological response. Conclusion: Combined use of root-cause analysis and molecular epidemiology was effective in ascertaining the origin of the HCV outbreak. Antiviral therapy avoided the chronic progression of the infection and further spread in care units and in the family environment.
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- 2021
11. Antibodies Responses to SARS-CoV-2 in a Large Cohort of Vaccinated Subjects and Seropositive Patients
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Francesco Vitale, Stefano Pizzo, Giuseppe Calamusa, Dario Genovese, Alessandra Casuccio, Donatella Ferraro, Emanuele Amodio, Floriana Bonura, Giuseppina Capra, Giovanni M. Giammanco, Simona De Grazia, Amodio, Emanuele, Capra, Giuseppina, Casuccio, Alessandra, Grazia, Simona De, Genovese, Dario, Pizzo, Stefano, Calamusa, Giuseppe, Ferraro, Donatella, Giammanco, Giovanni Maurizio, Vitale, Francesco, and Bonura, Floriana
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0301 basic medicine ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,viruses ,Immunology ,Article ,Serology ,Persistence (computer science) ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,Drug Discovery ,Medicine ,Pharmacology (medical) ,030212 general & internal medicine ,skin and connective tissue diseases ,Pharmacology ,antibody concentrations ,biology ,business.industry ,Immunogenicity ,SARS-CoV-2 infection ,fungi ,respiratory tract diseases ,Vaccination ,body regions ,030104 developmental biology ,Infectious Diseases ,Immunization ,biology.protein ,Antibody ,business ,COVID-19 vaccine - Abstract
COVID-19 is a current global threat, and the characterization of antibody response is vitally important to update vaccine development and strategies. In this study we assessed SARS-CoV-2 antibody concentrations in SARS-CoV-2 positive patients (N = 272) and subjects vaccinated with the BNT162b2 m-RNA COVID-19 vaccine (N = 1256). For each participant, socio-demographic data, COVID-19 vaccination records, serological analyses, and SARS-CoV-2 infection status were collected. IgG antibodies against S1/S2 antigens of SARS-CoV-2 were detected. Almost all vaccinated subjects (99.8%) showed a seropositivity to anti-SARS-COV-2 IgG and more than 80% of vaccinated subjects had IgG concentrations >, 200 AU/mL. In a Tobit multivariable regression analysis, SARS-CoV-2 vaccination was statistically significantly associated with increased IgG concentrations (β coef = 266.4, p <, 0.001). A statistically significant reduction in SARS-CoV-2 IgG concentrations was found with older age (β coef = −1.96 per year increase, 0.001), male sex (β coef = −22.3, 0.001), and days after immunization (β coef = −1.67 per day increase, 0.001). Our findings could support the vaccination campaigns confirming the high immunogenicity of the SARS-CoV-2 vaccine under investigation with respect to the natural infection. Further studies will be required for evaluating the role of age and days after immunization in the persistence of vaccine antibodies and protection from the disease.
- Published
- 2021
12. Antibodies Responses to SARS-CoV-2 in a Large Cohort of Vaccinated Subjects and Seropositive Patients
- Author
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Floriana Bonura, Giuseppe Calamusa, Giuseppina Capra, Alessandra Casuccio, Donatella Ferraro, Giovanni M. Giammanco, Stefano Pizzo, Dario Genovese, and Emanuele Amodio
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biology ,business.industry ,Immunogenicity ,Disease ,Serology ,Persistence (computer science) ,Vaccination ,Antigen ,Immunization ,Immunology ,biology.protein ,Medicine ,Antibody ,business - Abstract
Background: COVID-19 is a current global threat and characterisation of antibody response to SARS-CoV-2 is vitally important to update vaccine development and strategies. Methods: In this study we assessed SARS-CoV-2 antibody concentrations in SARS-CoV-2 positive patients (N=272) and subjects vaccinated with BNT162b2 m-RNA Covid-19 vaccine (N=1,256). For each participant socio-demographic data, COVID-19 vaccination records, serological analyses and SARS-CoV-2 infection status have been collected. IgM and IgG antibodies against S1/S2 antigens of SARS-CoV-2 were detected. Findings: Almost all vaccinated subjects (99·8%) showed a seropositivity to anti-SARS-COV-2 IgG and more than 80% vaccinated subjects had IgG concentrations >200 AU/mL. SARS-CoV-2 subjects had IgG concentrations
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- 2021
13. Phylodynamic Analysis and Implication of HCV Genotype 4 Variability on Antiviral Drug Response and T-Cell Recognition
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Donatella Ferraro, Vito Di Marco, Noemi Urone, Giuseppina Maria Elena Colomba, Colomba G.M.E., Urone N., Di Marco V., and Ferraro D.
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Settore MED/07 - Microbiologia E Microbiologia Clinica ,T-Lymphocytes ,lcsh:QR1-502 ,Bayesian analysis ,Hepacivirus ,Viral Nonstructural Proteins ,lcsh:Microbiology ,Coalescent theory ,phylodynamic ,Genotype ,genetic variability ,Phylogeny ,Bayesian analysi ,media_common ,Settore MED/12 - Gastroenterologia ,virus diseases ,Middle Aged ,viral epitope ,Hepatitis C ,Host-Pathogen Interaction ,Infectious Diseases ,medicine.anatomical_structure ,Host-Pathogen Interactions ,HCV ,tMRCA ,Drug ,Adult ,medicine.drug_class ,media_common.quotation_subject ,T cell ,macromolecular substances ,Human leukocyte antigen ,Biology ,Antiviral Agents ,Article ,Young Adult ,T cell recognition ,Virology ,Drug Resistance, Viral ,medicine ,Humans ,Genetic variability ,genotype 4 ,Aged ,DAA ,Antiviral Agent ,Hepaciviru ,digestive system diseases ,viral epitopes ,Antiviral drug ,CD8 ,RAS - Abstract
Therapies for HCV care could change the prevalence and the geographic distribution of genotypes due to differences in Sustained Virologic Response (SVR). In this scenario, uncommon genotypes/subtypes, such as genotype 4, could spread from high-risk groups, replacing genotypes eradicated by antiviral drugs. Genotype eradication is also strongly influenced by the CD8+ T cell response. In this study, the genetic variability in HCV genotype 4 strains obtained from a cohort of 67 patients naï, ve to DAA therapy was evaluated. We found that the presence of resistance-associated substitutions (RAS) was able to affect drug responses. Next, using a prediction tool, viral mutations were identified by their ability, or lack thereof, to reduce the binding affinity with HLA, which affects T cell recognition. The Bayesian coalescent analysis suggested two different circulation clusters, one in risk groups (IDUs and MSM) and the other due to migration flows, dated to 1940 and 1915, respectively. Most of the RAS overlapped with HLA and a lack of binding mutations was observed in 96% of strains. This study describes the introduction of HCV genotype 4 in a region of the Mediterranean basin and evaluates how HCV genotype 4&rsquo, s genetic variability could affect the response of antiviral drugs and CD8+ T cell recognition.
- Published
- 2020
14. Characterization of measles virus strains circulating in Southern Italy (Palermo area, Sicily) between 2010 and 2011
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Claudia Colomba, Noemi Urone, Donatella Ferraro, Urone, N., Colomba, C., and Ferraro, D.
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Adult ,Male ,0301 basic medicine ,Microbiology (medical) ,Settore MED/07 - Microbiologia E Microbiologia Clinica ,Adolescent ,Genotype ,Sequence analysis ,030106 microbiology ,History, 21st Century ,Microbiology ,Measles ,Measles virus ,Young Adult ,03 medical and health sciences ,Genetic ,Measle ,Genetic variation ,Genetics ,medicine ,Humans ,Sicily ,Molecular Biology ,Measles virus intra-genotypes variability ,Phylogeny ,Ecology, Evolution, Behavior and Systematics ,biology ,Measles elimination ,Genetic Variation ,Outbreak ,Sequence Analysis, DNA ,biology.organism_classification ,medicine.disease ,Ecology, Evolution, Behavior and Systematic ,Virology ,language.human_language ,Geographic distribution ,Infectious Diseases ,Measles virus genotype ,Measles viru ,language ,RNA, Viral ,Female ,Sicilian ,Measles virus lineage ,Human - Abstract
Measles virus (MV) was classified in 24 genotypes that show a distinct geographic distribution. Genotypes contain multiple distinct lineages. In 2011 large outbreaks of measles occurred in Italy and in many European countries. Aims of this study are to analyze the intra-genotype variability and to follow the importation and the spread of new MV strains in Sicily. A fragment of 450. bps of MV C-terminal nucleoprotein was sequenced from sera of 73 Sicilian patients with symptomatic measles infections, occurred between 2010 and 2011. Five MV strains were D4 genotype and 68 were D8 genotype. The MV/D4 sequences were related to MV/D4-Enfield variant. Two lineages of MV/D8 genotypes, related to MV/D8-Villupuram variant and to a strain found in Birmingham in 2006 respectively, were identified. This is the first study that reports the co-circulation of different MV genotypes and lineages in Sicily suggesting multiple origins of the outbreak that occurred during 2010 and 2011 years.
- Published
- 2016
15. Role of IL-28B and inosine triphosphatase polymorphisms in efficacy and safety of Peg-Interferon and ribavirin in chronic hepatitis C compensated cirrhosis with and without oesophageal varices
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Donatella Ferraro, Vincenza Calvaruso, R. Di Stefano, Antonio Craxì, Rosaria Maria Pipitone, Stefania Grimaudo, and V. Di Marco
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medicine.medical_specialty ,Cirrhosis ,Hepatology ,Combination therapy ,business.industry ,Ribavirin ,medicine.disease ,Gastroenterology ,chemistry.chemical_compound ,Infectious Diseases ,chemistry ,Virology ,Internal medicine ,Immunology ,medicine ,Portal hypertension ,ITPA ,Varices ,Rapid Virologic Response ,business ,Prospective cohort study - Abstract
Summary. Genetic factors can influence the outcome of antiviral therapy in chronic hepatitis C (HCV). We evaluated the role of interleukin-28B single nucleotide polymorphisms (SNPs) and inosine triphosphatase (ITPA) gene variants in HCV cirrhosis treated with Peg-Interferon and ribavirin. A prospective cohort of 233 patients with compensated cirrhosis received 1–1.5 μg/kg/week of Peg-Interferon alpha-2b plus 1000–1200 mg/day of RBV for 48 weeks. A sustained virologic response (SVR) was achieved in 27% of patients. On multivariate logistic analysis, the absence of oesophageal varices (OR 3.64 CI 95% 1.27–10.44 P = 0.016), infection with genotype 2 or 3 (OR 4.06, CI 95% 1.08–15.26, P = 0.038), C/C alleles of rs12979860 SNP (OR 7.04, CI 95% 2.40–20.72, P
- Published
- 2012
16. Hepatic steatosis and insulin resistance are associated with severe fibrosis in patients with chronic hepatitis caused by HBV or HCV infection
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Salvatore Petta, Fabio Salvatore Macaluso, Giuseppe Pizzolanti, Donatella Ferraro, Vito Di Marco, G. Venezia, Beatrice Belmonte, Rosa Di Stefano, Daniela Cabibi, Carla Guarnotta, Marcello Maida, Antonio Craxì, and Calogero Cammà
- Subjects
medicine.medical_specialty ,Hepatology ,medicine.diagnostic_test ,business.industry ,Disease ,medicine.disease ,Gastroenterology ,Insulin resistance ,HBeAg ,Fibrosis ,Liver biopsy ,Internal medicine ,Biopsy ,Immunology ,medicine ,Steatosis ,business ,Body mass index - Abstract
Background and aims: Steatosis and insulin resistance (IR) are the major disease modifying in patients with chronic hepatitis C (CHC). Only few studies evaluated these features in patients with chronic hepatitis B (CHB). We aimed to assess the prevalence and the factors related to steatosis and IR in CHB patients, compared with CHC subjects, and to evaluate the potential association between these features and fibrosis severity. Material and methods: One hundred and seventy consecutive patients with CHB (28 HBeAg positive, 142 HBeAg negative), were evaluated using liver biopsy and metabolic measurements and matched for sex, age and body mass index with 170 genotype 1 CHC patients. IR was defined if HOMA-IR>2.7. All biopsies were scored for grading and staging by Scheuer's score, and the steatosis was considered significant if ≥10%. Results: The prevalence of significant steatosis was similar in both CHB and CHC patients (31 vs. 38%; P=0.14). IR rate was significantly higher in CHC than in CHB patients (42 vs. 26%; P=0.002). Severe fibrosis (F3–F4), at multivariate analysis, was independently associated with older age (OR 1.050, 95% CI 1.009–1.093), steatosis >10% (OR 4.375, 95% CI 1.749–10.943), and moderate–severe necroinflammatory activity (OR 8.187, 95% CI 2.103–31.875), regardless of HBeAg status, in CHB patients, and with older age (OR 1.080, 95% CI 1.028–1.136), IR (OR 2.640, 95% CI 1.110–6.281), steatosis >10% (OR 3.375, 95% CI 1.394–8.171), and moderate–severe necroinflammatory activity (OR 8.988, 95% CI 1.853–43.593) in CHC patients. Conclusions: CHB patients had high steatosis prevalence, similar to CHC controls, but lower IR rate. Both steatosis and IR in CHC, and only steatosis in CHB, are independently associated with fibrosis severity.
- Published
- 2011
17. The impact of insulin resistance, serum adipocytokines and visceral obesity on steatosis and fibrosis in patients with chronic hepatitis C
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Piero Luigi Almasio, O. Lo Iacono, Salvatore Petta, Vito Rodolico, Maria Pia Amato, Carla Giordano, C. Mineo, Donatella Ferraro, Antonio Craxì, G. Venezia, S. De Lisi, and V. Di Marco
- Subjects
medicine.medical_specialty ,Hepatology ,Adiponectin ,business.industry ,Leptin ,Insulin ,medicine.medical_treatment ,Gastroenterology ,Adipokine ,medicine.disease ,Insulin resistance ,Endocrinology ,Fibrosis ,Internal medicine ,medicine ,Pharmacology (medical) ,Resistin ,Steatosis ,business - Abstract
SUMMARY Aims To assess whether host metabolic factors influence the degree of hepatic steatosis and fibrosis in patients infected with hepatitis C virus, and to evaluate the impact of anti-viral therapy on insulin resistance and serum levels of adipocytokines. Methods Clinical and biochemical features, anthropometrical characteristics, and levels of fasting insulin, leptin, adiponectin and resistin were measured in ‘naive’ patients with chronic hepatitis C, before, during and after therapy with Peg-Interferon-alpha 2a plus Ribavirin. Results Forty-eight patients were included (M/F 28/20; mean age 50.0 ± 12.6 years; 62.5% genotype-1). Body mass index was 26.4 ± 4.0 kg/m2, and visceral obesity was present in 24 patients. At multivariate analysis (RR; 95% CI), steatosis was associated to older age (1.08; 1–1.18), necroinflammatory activity (17.67; 1.6–194.46), and raised insulin levels (1.39; 1.1–1.77). Fibrosis was related to necroinflammatory activity (25.73; 2.54–261.11), and steatosis (6.47; 1.09–38.29). Sustained viral response was achieved by 62.5% of patients and was associated with younger age (0.92; 0.85–0.99), genotype non-1 (10.61; 1.52–73.76) and absence of visceral obesity (13.78; 2.36–80.29). At the end of follow-up, insulin and the homeostasis model assesment for insulin resistance were reduced and adiponectin increased when compared with baseline, all unrelated to the outcome of treatment. Conclusions Visceral obesity correlates with the degree of steatosis and fibrosis, and it negatively affects treatment response. Significant changes of insulin resistance and adipocytokines occur under treatment, irrespective of virological outcome.
- Published
- 2007
18. Effects of Eradicating Hepatitis C Virus Infection in Patients With Cirrhosis Differ With Stage of Portal Hypertension
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Antonio Craxì, S. Peralta, F. Simone, Giuseppe Cabibbo, Elisabetta Conte, Vincenza Calvaruso, Rosaria Maria Pipitone, A. Arini, Donatella Ferraro, Calogero Cammà, Vito Di Marco, M.G. Bavetta, Stefania Grimaudo, Di Marco, V., Calvaruso, V., Ferraro, D., Bavetta, M., Cabibbo, G., Conte, E., Cammà, C., Grimaudo, S., Pipitone, R., Simone, F., Peralta, S., Arini, A., and Craxì, A.
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Liver Cirrhosis ,Male ,Cirrhosis ,Sustained Virologic Response ,Hepacivirus ,Esophagu ,Gastroenterology ,Polyethylene Glycols ,Liver disease ,chemistry.chemical_compound ,0302 clinical medicine ,Esophageal varices ,Prospective Studies ,Prospective cohort study ,Hazard ratio ,virus diseases ,Middle Aged ,Portal Pressure ,Hepatitis C ,Recombinant Proteins ,Intention to Treat Analysis ,Italy ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,030211 gastroenterology & hepatology ,Female ,medicine.medical_specialty ,Interferon alpha-2 ,Lower risk ,Esophageal and Gastric Varices ,Antiviral Agents ,03 medical and health sciences ,Internal medicine ,Hypertension, Portal ,Ribavirin ,medicine ,Humans ,Aged ,Proportional Hazards Models ,Hepatology ,business.industry ,Bleeding ,Interferon-alpha ,Long-Term Outcome ,medicine.disease ,digestive system diseases ,chemistry ,business ,Follow-Up Studies - Abstract
Clearance of hepatitis C virus (HCV) via antiviral treatment changes the course of liver disease. We evaluated the benefit of sustained virologic response (SVR) in patients with HCV and cirrhosis without (stage 1) and with (stage 2) esophageal varices (EV).We performed a prospective cohort study of 444 patients with HCV and compensated cirrhosis (218 with stage 1 and 226 with stage 2 disease) treated with peg-interferon and ribavirin from June 2001 through December 2009 at the University of Palermo, Italy and followed for a median of 7.6 years (range, 1-12.6 years). We used Cox regression analysis to identify variables associated with appearance or progression of EVs, development of hepatocellular carcinoma (HCC), liver decompensation, and overall survival.In the intention-to-treat analysis, 67 patients with stage 1 disease (30.7%) and 41 patients with stage 2 disease (18.1%) achieved an SVR (P = .003). Patients with stage 1 disease and an SVR were less likely to develop EVs than stage 1 patients without an SVR (hazard ratio [HR], 0.23; 95% confidence interval [CI], 0.11-0.48; P.001). However, SVR did not affect whether patients with stage 2 disease developed further EVs (HR, 1.58; 95% CI, 0.33-1.03; P = .07, by log-rank test). An SVR was associated with lower risk for HCC (HR, 0.25; 95% CI, 0.12-0.55; P.001). Patients with stage 2 disease, regardless of SVR, were at greater risk than patients with stage 1 disease for liver decompensation (HR, 2.82; 95% CI, 1.73-4.59; P.001) or death (HR, 1.77; 95% CI, 1.12-2.80; P = .015). A lower proportion of patients with stage 1 disease and an SVR died from HCC (2.9%), compared with those without an SVR (11.9%) (P = .03) or developed liver decompensation (none vs 7.1% without an SVR; P = .009). A lower proportion of patients with stage 2 disease and an SVR died from causes secondary to HCC (2.0%) compared with those without an SVR (18.4%) (P = .003). Death from causes secondary to liver decompensation did not differ significantly between patients with stage 2 disease with or without an SVR (12.1% vs 25.4%; P = .15).In a prospective study of 444 patients with HCV and compensated cirrhosis, HCV eradication reduced risk for liver decompensation, HCC, and death, regardless of whether the patients had EVs.
- Published
- 2015
19. Impact of HBV genotypes A and D genetic variability on infection evolution
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Vito Di Marco, Bruno Cacopardo, Antonio Craxì, Noemi Urone, Donatella Ferraro, Urone, N., Di Marco, V., Cacopardo, B., Craxì, A., and Ferraro, D.
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Adult ,Male ,Microbiology (medical) ,Hepatitis B virus ,Settore MED/07 - Microbiologia E Microbiologia Clinica ,Genotype ,Acute hepatitis B ,Biology ,medicine.disease_cause ,Microbiology ,Liver disease ,Viral Proteins ,preC/C mutation ,Genetic ,Immune-escape mutation ,Genetic variation ,Genetics ,medicine ,Humans ,Viral Protein ,Genetic variability ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Phylogeny ,Aged ,Polymorphism, Genetic ,preS/S mutation ,Genetic Variation ,Hepatitis B viru ,Hepatitis B ,Middle Aged ,medicine.disease ,Virology ,Biological Evolution ,Ecology, Evolution, Behavior and Systematic ,Infectious Diseases ,Amino Acid Substitution ,Viral evolution ,Immunology ,Mutation ,Female ,Viral hepatitis ,Human - Abstract
HBV is characterized by a high genetic variability, which is the basis of its classification into eight genotypes (A-H). HBV infection is associated with different outcomes, from self-limiting acute hepatitis to active chronic hepatitis, asymptomatic carriage, and occult infection. The aim of this study was to analyze the genetic variability of HBV genotypes A and D isolates from 79 cases of self-limiting acute hepatitis and chronic hepatitis, in order to identify HBV variants associated with resolution or chronicity of acute HBV infection. The entire preS-S sequence and a fragment of 346 bp of the preC-C region, containing Enhancer II and Basal Core Promoter sequences, were analyzed. A phylogenetic analysis of preS/S region showed that the 45.45% (15/33) of isolates from acute hepatitis cases were genotype A compared to 8.69% (4/46) of chronic hepatitis cases. (p = 0.0002). Mutations associated with immune-escape (T131N, D144A/E, G145K), amino acid polymorphisms in "a determinant" domain of S protein and mutations/deletions in preC/C region were found in isolates from acute and chronic hepatitis B cases. In this study mutations/deletions in preS-S and preC-C regions, usually associated with fulminant acute hepatitis, advanced forms of liver disease and increased risk for HCC, were identified in HBV strains of genotype A and D obtained both from patients with self-limiting acute HBV infection and from persistent infected patients. This founding probably is due to the natural viral evolution under host immune response and to the circulation of a wide variety of HBV strains in our geographic area because of the ancient introduction of genotype D and the migrant fluxes from North Africa. Moreover, the analysis of circulation of new HBV antigenic variants is fundamental for the epidemiological surveys and for the evaluation of the impact of viral evolution on vaccine prophylaxis strategies.
- Published
- 2015
20. HCV-1b intra-subtype variability: Impact on genetic barrier to protease inhibitors
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Vito Di Marco, Donatella Ferraro, Noemi Urone, Antonio Craxì, Ferraro, D, Urone, N, Di Marco, V, and Craxì, A
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Male ,Microbiology (medical) ,Settore MED/07 - Microbiologia E Microbiologia Clinica ,medicine.medical_treatment ,Population ,Locus (genetics) ,Hepacivirus ,Intra-subtype variability ,Viral Nonstructural Proteins ,Biology ,Microbiology ,HCV genetic barrier ,NS3 sequencing ,Drug Resistance, Viral ,Genetics ,medicine ,Humans ,Genetic variability ,Transversion ,education ,Molecular Biology ,Gene ,Phylogeny ,Ecology, Evolution, Behavior and Systematics ,Aged ,education.field_of_study ,NS3 ,Protease ,Wild type ,Genetic Variation ,virus diseases ,Hepatitis C, Chronic ,Middle Aged ,Protease inhibitors ,Virology ,IFN-free therapy ,Infectious Diseases ,Mutation ,Female - Abstract
Due to error-prone RNA polymerase and the lack of proofreading mechanisms, to the spread worldwide and probable long-term presence in human population, HCV showed a high degree of inter- and intra-subtype genetic variability. Protease inhibitors (PIs), a new class of drugs, have been designed specifically on the HCV genotype 1 NS3 protease three-dimensional structure. The viral genetic barrier limits the efficacy of PIs, and fourteen loci in the HCV NS3 gene are involved in resistance to PIs. A sensitive method (15 UI/ml) for study the HCV genetic profile of 125 strains from patients naive to PIs, was developed through the use of new degenerate primers for subtype 1b. We observed the presence of naturally resistance-associated variants in 14% of the HCV strains (V36L, F43S, T54S, I153V, R155Q, D168A/G). T54S was the most common mutation (4%) detected. We investigated, through minimal score ( m.s .) calculating, how the HCV intra-subtype 1b variability modifies the genetic barrier to PIs. For >60% of strains a single transition ( m.s. of 1) was required for selection of low to medium resistance mutations, while more than one transition/transversion ( m.s. ⩾2.5) or one transition plus one transversion ( m.s. ⩾3.5) was necessary for most of the high level PI-resistant-associated mutations, except for A156V, for which a single transition was sufficient ( m.s. of 1). However, the presence at locus 36 of the amino acid polymorphism S36 in one case and the wild type V36 in 6 isolates, encoded by unusual GTA or GTG codons, might determined a higher probability of V36L/M mutations because of the reduction of the genetic barrier. Instead, the presence of the CGA and CGT codons in the 155 th position increases the genetic barrier for R155M or R155Q/M. The large intra-subtype variability, suggests that a routine baseline resistance test must be used before PIs-treatment.
- Published
- 2014
21. High-dose prolonged combination therapy in non-responders to interferon monotherapy for chronic hepatitis C
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Vito Rodolico, V. Di Marco, Alessandra Vaccaro, R. Di Stefano, Giuseppe Alaimo, P. Parisi, P.L. Almasio, Donatella Ferraro, Antonio Craxì, and S. Peralta
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medicine.medical_specialty ,Chemotherapy ,Hepatology ,Combination therapy ,business.industry ,medicine.medical_treatment ,Ribavirin ,Gastroenterology ,Alpha interferon ,Surgery ,chemistry.chemical_compound ,Regimen ,chemistry ,Tolerability ,Internal medicine ,medicine ,Pharmacology (medical) ,Adverse effect ,business ,Interferon alfa ,medicine.drug - Abstract
Background: Therapy of chronic hepatitis C non- responders to interferon monotherapy with standard doses of interferon plus ribavirin is usually ineffective. Aim: To evaluate the efficacy and tolerability of high-dose prolonged combination retreatment in non- responder patients. Methods: Patients were retreated for 6 months with 6 MU αIFN on alternate days and 1000 or 1200 mg/day ribavirin. HCV-RNA negative patients continued therapy for an additional 6 months. Results: Forty patients (29 males, mean age 49.7 years, 34 genotype 1b, 11 with F3 fibrosis) were treated. At 6 months, 20 (50%) patients were HCV-RNA negative but six of them discontinued therapy because of adverse events. A sustained response was achieved in 28% of patients (11/40). A sustained response was more frequent among patients with genotype non-1b than in those with genotype 1b (67 vs. 21%, P=0.005) and clearance of HCV-RNA in the first 3 months had a high predictive value for sustained response (100% of sustained responders vs. 24% of non-responders, P=0.0001). Conclusions: High-dose prolonged combination therapy in non-responders to IFN monotherapy leads to a higher rate of sustained response than the standard combination regimen. Tolerability may be a rate-limiting factor. Maximal effectiveness can be predicted in patients with non-1b genotype and in those who clear HCV-RNA soon after starting retreatment.
- Published
- 2001
22. No detection of occult HBV-DNA in patients with various rheumatic diseases treated with anti-TNF agents: a two-year prospective study
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Giardina, A. R., Donatella Ferraro, Ciccia, F., Ferrante, A., Di Stefano, R., Craxì, A., Triolo, G., Giardina, A., Ferraro, D., Ciccia, F., Ferrante, A., Di Stefano, R., Craxi, A., Triolo, G., Giardina, Annarita, Ferraro, Donatella, Ciccia, Francesco, Ferrante, Angelo, Di Stefano, R, Craxi, Antonio, and Triolo, Giovanni
- Subjects
Adult ,Male ,Hepatitis B virus ,Time Factors ,occult HBV-DNA ,Antiviral Agents ,Polymerase Chain Reaction ,Risk Assessment ,Risk Factors ,Rheumatic Diseases ,occult HBV-DNA, rheumatic diseases, anti-TNF ,Humans ,Prospective Studies ,rheumatic disease ,Academic Medical Centers ,Hepatitis B Surface Antigens ,Tumor Necrosis Factor-alpha ,virus diseases ,anti-TNF ,Middle Aged ,Hepatitis B ,digestive system diseases ,Treatment Outcome ,Italy ,Lamivudine ,Antirheumatic Agents ,DNA, Viral ,Female ,Virus Activation ,Biomarkers - Abstract
OBJECTIVES: The widespread use of tumour necrosis factor (TNF)-targeted therapies in patients with rheumatic, digestive and dermatologic diseases has been associated with reports of reactivation of HBV replication and ensuing hepatitis flares both in asymptomatic HBsAg carriers and in subjects with occult HBV infection. The aim of our work was to investigate in a two-year prospective study the potential for HBV reactivation in patients with inflammatory joint diseases undergoing anti-TNF treatment from a southern Mediterranean area. METHODS: Fifty-seven consecutive outpatients attending the Academic Unit of Rheumatology at the University of Palermo (12 with rheumatoid arthritis, 17 with psoriatic arthritis and 28 with ankylosing spondylitis) were enrolled in the study. HBV-DNA was tested by a standard quantitative assay in HBsAg-positive subjects and by an ad hoc highly sensitive PCR in HBsAg-negative patients performed at baseline and then every six months on the anti-TNF agent. RESULTS: Occult HBV-DNA was never detected in the 54 HBsAg negative subjects, regardless of their anti HBs/HBc status. All HBsAg positive patients, who were started on prophylactic lamivudine, remained HBV-DNA undetectable throughout the anti-TNF treatment. CONCLUSIONS: Even in an area of previously high HBV endemicity, where occult HBV infection is likely to have a high prevalence, treatment of rheumatological patients with anti-TNF drugs is safe in terms of its potential to reactivate HBV. Prophylaxis with lamivudine is sufficient to prevent reactivation in HBsAg carriers.
- Published
- 2013
23. Viral Sequence Analysis of Occult HBV Infection and Its Reactivation in Immunosuppressed Patients
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Donatella Ferraro, Pizzillo, P., Urone, N., Iannitto, E., Craxí, A., Di Stefano, R., Ferraro, D., Pizzillo, P., Urone, N., Iannitto, E., Craxi, A., and DI STEFANO, R.
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Male ,Hepatitis B virus ,Settore MED/07 - Microbiologia E Microbiologia Clinica ,Settore MED/12 - Gastroenterologia ,Genotype ,occult HBV, HBV reactivation, phylogenetic analysis,molecular epidemiology ,Genetic Variation ,Sequence Analysis, DNA ,Hepatitis B ,Immunocompromised Host ,DNA, Viral ,Humans ,Female ,Retrospective Studies - Abstract
Mechanisms associated with reactivation of hepatitis B virus (HBV) in patients with occult HBV infection (OBI) remain unclear. In some cases immunosuppression is an enhancer of viral replication. However, not all patients with OBI who undergo immunosuppression experience reactivation. This study explores the role of viral heterogeneity as a determinant of occult HBV reactivation. HBV genotype, mutation patterns and quasispecies were assessed by sequencing the PreS/S region of 16 patients with OBI undergoing chemotherapy, 3 of whom experienced a OBI reactivation. The latter were also assessed at the time of reactivation. Phylogenetic analysis identified low nucleotide and amino acid diversity rates. There were no differences in the viral quasispecies, or common mutation patterns, detected between patients who underwent reactivation of OBI, and those who did not. Furthermore, upon reactivation, the quasispecies evolved towards a loss of most of the variants present during the initial OBI stage, probably representing the fittest version of the virus. The genetic variability of HBV alone did not account for the transition from occult to overt infection, which appears to be governed principally by the host immune response.
- Published
- 2013
24. Phylogenetic Analysis of isolates from new cases of HBV infection in Southern Italy
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M. Gussio, Rosa Di Stefano, Antonio Craxì, Noemi Urone, Salvatore Magliocco, Vito Di Marco, Paola Pizzillo, Donatella Ferraro, Bruno Cacopardo, Ferraro D, Urone N, Pizzillo P, Gussio M, Magliocco S, Cacopardo B, Craxì A, Di Marco V, and Di Stefano, R
- Subjects
Microbiology (medical) ,Adult ,Male ,medicine.medical_specialty ,Hepatitis B virus ,Settore MED/07 - Microbiologia E Microbiologia Clinica ,Genotype ,Biology ,medicine.disease_cause ,Microbiology ,Liver disease ,Epidemiology ,Genetics ,medicine ,Humans ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Phylogeny ,Aged ,Aged, 80 and over ,Molecular Epidemiology ,Settore MED/12 - Gastroenterologia ,Molecular epidemiology ,Phylogenetic tree ,Sequence Analysis, DNA ,Hepatitis B ,Middle Aged ,medicine.disease ,Virology ,Infectious Diseases ,Italy ,Immunology ,DNA, Viral ,Female ,Viral hepatitis ,HBV genotypes, molecular epidemiology, Acute HBV infection, phylogenetic analysis - Abstract
The level of endemicity of hepatitis B virus (HBV) infections in Italy is low and genotype D infections predominant. New HBV strains may however be introduced as a result of movements of people from regions of high endemicity. The aim of the present study was to determine whether strains from new cases of acute hepatitis B detected in southern Italy were due to endemic or new HBV strains. We studied 34 isolates from patients with acute hepatitis B infection, and 35 from chronic hepatitis B patients. A phylogenetic analysis of preS/S region was done by comparing the sequences from the acute and chronic cases with references sequences. The study showed that 44% of strain from acute hepatitis B patients were of genotype A, 53% of genotype D, and 3% of genotype E. The molecular analysis of isolates from acute hepatitis B patients from Sicily showed a change in the local epidemiology of this infection, with an increase in HBV/A infections and a clustering effect for HBV D2, possibly correlated to immigration. The introduction of new genotypes , could have an effect on HBV-correlated diseases due to the different association between genotype, liver disease and response to antiviral therapy.
- Published
- 2012
25. Fibrosis evaluation by transient elastography in patients with long-term sustained HCV clearance
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Anna Calì, Vincenza Calvaruso, Salvatore Petta, Piero Luigi Almasio, Elisabetta Conte, Donatella Ferraro, Vito Di Marco, M.G. Bavetta, Calvaruso, V, Di Marco, V, Ferraro, D, Petta, S, Calì, A, Bavetta, MG, Conte, E, and Almasio, PL
- Subjects
Liver Cirrhosis ,medicine.medical_specialty ,Pathology ,Cirrhosis ,Gastroenterology ,chemistry.chemical_compound ,Fibrosis ,Internal medicine ,Biopsy ,Medicine ,Stage (cooking) ,Hepatology ,medicine.diagnostic_test ,business.industry ,Ribavirin ,medicine.disease ,Kowsar ,liver stiffness ,Infectious Diseases ,chemistry ,Elasticity Imaging Techniques ,Steatosis ,Insulin Resistance ,business ,Transient elastography ,Research Article - Abstract
Background: Reversibility of advanced fibrosis after HCV-clearance is an important goal of therapy. Objectives: Measuring liver stiffness (LS) by transient elastography (TE) might be helpful in this setting. Patients and Methods: We evaluated 104 patients with biopsy-proven chronic hepatitis C (CHC) and sustained virological response (SVR) after Peg-Interferon (IFN) plus ribavirin since at least 18 months. HCV-eradication was confirmed searching for serum HCV-RNA (TMA® sensitivity > 5-10 IU/ml). Data from literature reported the best LS cut-off values for different stages of liver fibrosis were 7.1 kPa for Metavir stage 2 (F2), 9.5 kPa for F3 and 12.5 for cirrhosis (F4). Results: TE was not reliable in four SVR obese patients. Metavir-stage of biopsy was F0-1 in 28, F2 in 47, F3 in 17 and F4 in eight patients. The median interval elapsed since achieving SVR was 36 months (range: 18-77, SD¬¬:18). Stratifying patients according to the histological stage assessed before treatment, a clear-cut gradient of LS values was observed from F0-1: median: 3.8 kPa (range: 3.5-4.9) to F2: 4.6 kPa (3.8-6.0), F3: 6.2 kPa (4.8-8.6) and F4: 8.4 kPa (6.2-9.2) (P = 0.001). Overall, 86 patients had lower values of LS than the expected LS values according to Metavir-stage. At multivariate logistic analysis γ-GT and histological steatosis were independently associated with persistence of higher values of LS. Conclusion: Long term responders to IFN-based therapies have lower LS values than those who are untreated and still viraemic. High levels of γ-GT and liver steatosis, all markers of insulin resistance, may hamper reduction of liver stiffness after HCV-clearance.
- Published
- 2012
26. Vitamin D levels and IL28B polymorphisms are related to rapid virological response to standard of care in genotype 1 chronic hepatitis C
- Author
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A. Mazzola, Stefania Grimaudo, Daniela Cabibi, Concetta Scazzone, Antonietta Di Cristina, Antonio Craxì, Calogero Cammà, Donatella Ferraro, Rosa Di Stefano, Vito Di Marco, Massimo Levrero, and Salvatore Petta
- Subjects
Adult ,Male ,Standard of care ,Genotype ,Hepacivirus ,Antiviral Agents ,Polymorphism, Single Nucleotide ,Polyethylene Glycols ,Virological response ,chemistry.chemical_compound ,Chronic hepatitis ,Pegylated interferon ,Risk Factors ,Vitamin D and neurology ,Medicine ,Humans ,Pharmacology (medical) ,Vitamin D ,Pharmacology ,business.industry ,Ribavirin ,Interleukins ,Interferon-alpha ,Standard of Care ,Hepatitis C, Chronic ,Middle Aged ,Viral Load ,Recombinant Proteins ,Infectious Diseases ,Treatment Outcome ,chemistry ,Immunology ,Female ,Interferons ,business ,medicine.drug - Abstract
Background Genotype 1 (G1) chronic hepatitis C (CHC) patients achieving a rapid virological response (RVR) on pegylated interferon (PEG-IFN) plus ribavirin have a high chance of sustained virological response (SVR), influenced by IL28B status, viral load, fibrosis and insulin resistance. We assessed whether 25-hydroxyvitamin D (25[OH]D) serum levels are linked to RVR and can be used together with IL28B to construct a pretreatment model to predict RVR. Methods A total of 117 consecutive patients with G1 CHC were evaluated by biopsy and anthropometric and metabolic measurements. 25(OH)D serum levels were measured by HPLC. IL28B rs12979860 and rs8099917 polymorphisms were also evaluated. All patients underwent antiviral therapy with PEG-IFN-α2a plus ribavirin. HCV RNA was assessed at baseline, week 4, week 12, at the end of therapy and after 6 months of follow-up. Results Mean ±sd 25(OH)D serum levels were 26.3 ±10.6 μg/l (range 8.0–58.0) and 31 (26.5%) patients had the rs12979860 CC polymorphism. RVR was achieved in 35 (29.9%) patients, and 32 (91.4%) of them had an SVR, compared to 26 of 82 (31.7%) without RVR. The rs12979860 CC polymorphism (OR 4.575, 95% CI 1.761, 11.889; P=0.002) and higher 25(OH)D levels (OR 1.055, 95% CI 1.010, 1.101; P=0.01) were independently associated with the achievement of RVR by multivariate analysis. The likelihood of RVR progressively increased from patients in the worst class (vitamin DConclusions In patients with G1 CHC, 25(OH)D serum levels and IL28B status are independently associated with the likelihood to achieve RVR and SVR. When incorporated into a pretreatment predictive model they can assist in further discriminating patients with a high likelihood of achieving RVR and SVR.
- Published
- 2011
27. Liver disease in chelated transfusion-dependent thalassemics: the role of iron overload and chronic hepatitis C
- Author
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Piero Luigi Almasio, Zelia Borsellino, Giovanni Battista Ruffo, Rosa Di Stefano, Francesco Gagliardotto, Antonio Craxì, Donatella Ferraro, Fabrizio Bronte, Vito Di Marco, F. Barbaria, Liana Cuccia, Marcello Capra, Daniela Cabibi, DI MARCO V, CAPRA M, GAGLIARDOTTO F, BORSELLINO Z, CABIBI D, BARBARIA F, FERRARO D, CUCCIA L, RUFFO GB, BRONTE F, DI STEFANO R, ALMASIO PL, and CRAXÌ A
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Adult ,Liver Cirrhosis ,Male ,Liver Iron Concentration ,Cirrhosis ,Iron Overload ,Adolescent ,Hepatitis C virus ,Biopsy ,Hepacivirus ,Settore MED/08 - Anatomia Patologica ,medicine.disease_cause ,Cohort Studies ,Liver disease ,thalassemic, iron, chronic hepatitis C ,Medicine ,Humans ,Retrospective Studies ,Settore MED/12 - Gastroenterologia ,medicine.diagnostic_test ,business.industry ,Transfusion Reaction ,Hematology ,Hepatitis C ,Hepatitis C, Chronic ,Viral Load ,medicine.disease ,Liver ,Liver biopsy ,Immunology ,Splenectomy ,Thalassemia ,Female ,business ,Hepatic fibrosis ,Viral load - Abstract
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
- Published
- 2008
28. Different doses of consensus interferon plus ribavirin in patients with hepatitis C virus genotype 1 relapsed after interferon monotherapy: a randomized controlled trial
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Vincenza Calvaruso, Vito Di Marco, Francesca D’Angelo, Salvatore Porrovecchio, Antonio Craxì, Rosa Di Stefano, Donatella Ferraro, Giuseppe Alaimo, Piero Luigi Almasio, Alaimo, G., DI MARCO, V., Ferraro, D., DI STEFANO, R., Porrovecchio, S., D'Angelo, F., Calvaruso, V., Craxi, A., and Almasio, P.
- Subjects
Adult ,Male ,medicine.medical_specialty ,Settore MED/07 - Microbiologia E Microbiologia Clinica ,viruses ,Hepacivirus ,Alpha interferon ,Pharmacology ,Gastroenterology ,Antiviral Agents ,Drug Administration Schedule ,law.invention ,chemistry.chemical_compound ,Randomized controlled trial ,law ,Interferon ,Recurrence ,Internal medicine ,Ribavirin ,medicine ,Humans ,In patient ,Settore MED/12 - Gastroenterologia ,biology ,Dose-Response Relationship, Drug ,business.industry ,Interferon-alpha ,General Medicine ,Hepatitis C, Chronic ,Middle Aged ,Viral Load ,biology.organism_classification ,humanities ,Recombinant Proteins ,Treatment Outcome ,chemistry ,Interferon Type I ,Interferon, Ribavirin, Hepatitis C virus, Hepatitis C, Relapser ,Drug Therapy, Combination ,Female ,business ,Viral load ,Interferon type I ,Rapid Communication ,medicine.drug - Abstract
AIM: To assess the efficacy of different schedules of consensus interferon (CIFN) plus ribavirin in retreating chronic hepatitis C patients who relapsed after recombinant interferon (rIFN) monotherapy. METHODS: Forty-five patients (34 males and 11 females) with chronic hepatitis due to hepatitis C virus (HCV) genotype 1 who relapsed after a previous course of rIFN monotherapy were randomized to receive 9 μg CIFN three times per week for 52 wk (group A, n = 22) or 18 μg CIFN three times per week for 52 wk (group B, n = 23) in combination with ribavirin 800 to 1200 mg daily for 52 wk (according to body weight). Virological response was evaluated at week 24 (EVR), at the end of treatment (ETR) and at 76 wk (SVR). RESULTS: By intention-to-treat analysis, subjects in group A had an EVR in 35% of cases, an ETR in 35% and a SVR in 27.3% of cases. Subjects in group B had an EVR in 32% of cases, an ETR in 35% and a SVR in 26.1% of cases. Treatment was stopped because of adverse effects (mostly intolerance) in 15 patients (6 in group A and 9 in group B). IFN dose reduction was needed in 2 patients (1 in group A and 1 in group B). Ribavirin dose was reduced in 2 patients in group A and 1 in group B respectively. Among the 15 subjects who received at least 80% of the intended schedule, the rate of SVR was 80% (6 in group A and 6 in group B). CONCLUSION: CIFN in combination with ribavirin when given to HCV genotype 1 relapsers after rIFN monotherapy obtains an unsatisfactory rate of sustained viral clearance independently of dosage of the drug. This may be due to its scarce tolerability.
- Published
- 2006
29. RUOLO DELL’INFEZIONE OCCULTA DA HBV NEL PAZIENTE IMMUNOCOMPROMESSO
- Author
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Paola Pizzillo, R. Di Stefano, Antonio Craxì, Emilio Iannitto, Viviana Minardi, Donatella Ferraro, F. Cardinale, Maria Giglio, FERRARO D, IANNITTO E, GIGLIO M, MINARDI U, CARDINALE F, PIZZILLO P, CRAXÌ A, and DI STEFANO R
- Subjects
lcsh:QR1-502 ,lcsh:Microbiology - Published
- 2005
30. VALUTAZIONE DELLA CLEARANCE DI HCV-RNA SOTTO TRATTAMENTO ANTIVIRALE CON TRANSCRIPTION-MEDIATED AMPLIFICATION (TMA)
- Author
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F. Cardinale, R. Di Stefano, V. Di Marco, Maria Giglio, Paola Pizzillo, Donatella Ferraro, and Antonio Craxì
- Subjects
lcsh:QR1-502 ,General Medicine ,lcsh:Microbiology - Published
- 2005
31. Identification of picobirnavirus from faeces of Italian children suffering from acute diarrhea
- Author
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Serenella Arista, Antonio Cascio, Michele Bosco, Donatella Ferraro, Anna Giammanco, Esmeralda Vizzi, A. CASCIO, BOSCO M, VIZZI E, GIAMMANCO A, FERRARO D, and ARISTA S
- Subjects
Diarrhea ,Male ,Acute diarrhea ,Epidemiology ,Picobirnavirus ,Microbiology ,Feces ,Picobirnavirus, Gastroenteritis, PAGE ,Humans ,Medicine ,Child ,Polyacrylamide gel electrophoresis ,Gel electrophoresis ,biology ,business.industry ,Brief Report ,biology.organism_classification ,Gastroenteritis ,PAGE ,Italy ,Virus Diseases ,RNA, Viral ,Electrophoresis, Polyacrylamide Gel ,Female ,Viral disease ,medicine.symptom ,business - Abstract
Polyacrylamide gel electrophoresis of nucleic acid extracted from stool samples of diarrhoeic children revealed in 3 out of 690 (0.43 %) specimens two electrophoretic bands with a migration pattern characteristic of picobirnavirus ds-RNA. In none of the 92 control children were similar bands detected. No other potential enteric pathogens were found in the patients with picobirnavirus infection.
- Published
- 1996
32. Anti-hepatitis A virus seroprevalence and seroconversion in a cohort of patients with chronic viral hepatitis
- Author
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Alfonso Mele, Tommaso Stroffolini, Anna Linda Zignego, Piero Luigi Almasio, S. Tripi, Giovanna Fattovich, Antonio Craxì, Filomena Morisco, G. Di Gaetano, Pietro Andreone, A. Smedile, Donatella Ferraro, R. Di Stefano, G.B. Gaeta, Stroffolini, T., Almasio, P., DI STEFANO, R., Andreone, P., Di Gaetano, G., Fattovich, G., Gaeta, G., Morisco, F., Smedile, A., Tripi, S., Zignego, A., Ferraro, D., Mele, A., Craxi, A., Stroffolini, T, Almasio, Pl, DI STEFANO, R, Andreone, P, DI GAETANO, G, Fattovich, G, Gaeta, Giovanni Battista, Morisco, F, Smedile, A, Tripi, S, Zignego, Al, Ferraro, D, and Mele, A
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Hepatitis C virus ,medicine.disease_cause ,Hepatitis A Antibodies ,Virus ,Hepatitis B, Chronic ,Seroepidemiologic Studies ,Internal medicine ,medicine ,Humans ,Seroconversion ,Fulminant hepatitis ,Aged ,Hepatitis B virus ,Hepatology ,business.industry ,Incidence ,Gastroenterology ,Hepatitis C ,Hepatitis B ,Hepatitis A ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,Virology ,Chronic liver disease ,Hepatitis A virus superinfection ,Italy ,Hepatitis A Antibodie ,Female ,business ,Viral hepatitis ,Hepatitis A Virus, Human ,Human - Abstract
Background. Patients with chronic hepatitis C infected by hepatitis A virus have a substantial risk of fulminant hepatitis or death, while the course of hepatitis A virus is uncomplicated in most subjects with chronic hepatitis B. Aim. To evaluate the prevalence of anti-hepatitis A virus antibodies and the incidence of hepatitis A virus seroconversion in a nationwide sample of 530 patients with chronic hepatitis B and/or hepatitis C infection initially susceptible to this infection after a follow-up of some years. Results. The overall anti-hepatitis A virus prevalence was 85.7%, with no difference between males and females. By the age of 50 years, almost all patients were found to have been exposed to hepatitis A virus. After a mean follow-up period of 76 months the overall anti-hepatitis A virus seroconversion rate in the 76 initially susceptible individuals was 1.2 per 100 person/years. However, it was 0.3 per 100 person/years in those hepatitis B surface antigen positive but 3.36 per 100 person/years in those anti-hepatitis C virus positive. None of the seroconverters was affected by a clinically evident disease or showed deterioration of underlying chronic liver disease. Conclusions. The present study shows that Italian patients > 50 years of age with chronic liver disease have already been exposed to hepatitis A virus suggesting that anti-hepatitis A virus screening is not advisable in these subjects.
- Published
- 2002
33. Hepatitis B Virus Reactivation and Alemtuzumab Therapy
- Author
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Viviana Minardi, Antonio Craxì, Emanuele Ammatuna, Rosellina Di Stefano, Antonino Mulè, Giuseppina Calvaruso, Emilio Iannitto, Vincenzo Abbadessa, and Donatella Ferraro
- Subjects
Hepatitis ,Hepatitis B virus ,HBsAg ,medicine.diagnostic_test ,CD52 ,business.industry ,Immunology ,virus diseases ,Lamivudine ,Cell Biology ,Hematology ,Hepatitis B ,medicine.disease ,medicine.disease_cause ,Biochemistry ,digestive system diseases ,Liver biopsy ,medicine ,Alemtuzumab ,business ,medicine.drug - Abstract
Reactivation of hepatitis B virus infection in subjects receiving cytotoxic treatment for haematological malignancies occurs in 21–53% of chronic HBsAg carriers and in an unknown number of HBsAg negative subjects harbouring occult HBV infection. Immunotherapy with alemtuzumab, a humanized monoclonal antibody against CD52 on lymphoid cells, produces deep immunosuppression. We describe two subjects with chronic lymphocytic leukaemia and occult HBV infection who developed a virological and biochemical flare of hepatitis B following immunotherapy with alemtuzumab. One of them developed a full blown hepatitis with seroreversion from anti-HBs to HBsAg after four weeks of alemtuzumab. Lamivudine (100 mg die) achieved a complete clinical recovery and HBV-DNA clearance from blood within 8 weeks. The second patient (HBsAg and HBV-DNA seronegative, anti-HBs and anti-HBc positive before treatment) was kept under prophylaxis with lamivudine up to three months after alemtuzumab. Two months after withdrawal of lamivudine, clinical and laboratory features of acute hepatitis B developed. Lamivudine therapy was restarted and obtained a prompt recovery with HBsAg and HBV-DNA clearance. These cases suggest that alemtuzumab, as all other immune response modifiers, should be used cautiously when HBV infection is present. While a recommendation for universal pre-emptive treatment with lamivudine of all HBsAg positive patients undergoing effective immunosuppressive treatment can be made it is more difficult to establish a pattern for patients who have serological markers of previous HBV infection (anti-HBs and/or anti-HBc) and even more for those with no HBV markers. Testing for HBV-DNA in serum by highly sensitive PCR may discover up to 50% of these cases, allowing preemptive lamivudine therapy. A substantial proportion would however go undiscovered in the absence of a liver biopsy, which is clearly an unfeasible proposition as a screening procedure. Once a reactivation has been documented, nucleoside analog therapy should last for a few months after HBV-DNA clearance.
- Published
- 2004
34. Schistosomiasis and antiviral treatment of chronic hepatitis C
- Author
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Donatella Ferraro, Vito Di Marco, Rosa Di Stefano, Francesco Gagliardotto, and Marcello Capra
- Subjects
Adult ,Hepatology ,business.industry ,Schistosomiasis ,Hepatitis C, Chronic ,medicine.disease ,Virology ,Chronic hepatitis ,Splenectomy ,Humans ,Medicine ,Interferons ,Antiviral treatment ,business - Published
- 2003
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