The effect of antiviral therapy on clinical outcome of HCV cirrhosis with portal hypertension: a prospective cohort study.

Early viral clearance and sustained response in chronic hepatitis C: a controlled trial of interferon and ribavirin after high-dose interferon induction

High-dose induction with alpha-interferon induces early viral clearance of hepatitis C and combined with ribavirin enhances sustained response. We assess whether adding ribavirin after viral clearance obtained by alpha-interferon induction increased the rate of viral eradication.Forty-one naïve patients with chronic hepatitis C were randomised to receive, after 4 weeks of 10 mU daily of alpha-interferon (induction), 3 mU daily for 22 weeks and 3 mU thrice weekly for 26 weeks of either interferon alone (monotherapy) or interferon plus 1000-1200 mg daily of ribavirin (combination therapy). At the end of the induction phase, 23 (56%) subjects had cleared HCV-RNA. During therapy, breakthrough w…

No detection of occult HBV-DNA in patients with various rheumatic diseases treated with anti-TNF agents: a two-year prospective study.

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 pso…

Infezione occulta da HBV in pazienti con malattie oncoematologiche

EVALUATING THE RISK OF HEPATITIS B REACTIVATION IN PATIENTS WITH HAEMATOLOGICAL MALIGNANCIES: IS THE SERUM HEPATITIS B PROFILE RELIABLE?

Background/Aim: Patients with an occult hepatitis B virus (HBV) infection undergoing deep immunosuppression are potentially at risk of HBV reactivation. In order to assess whether a polymerase chain reaction (PCR) assay for HBV DNA in serum could be used to predict the reactivation of an occult HBV infection, we performed a retrospective study in a cohort of Sicilian patients with oncohaematological diseases. Methods: We studied by a highly sensitive ad hoc nested PCR for serum HBV DNA 75 HBsAg-negative oncohaematological patients requiring chemotherapy. Results: Thirty-three patients (44%) were HBV seronegative (anti-HBc and anti-HBs negative) and 42 patients (56%) were HBV seropositive (a…

HBV-DNA suppression and disease course in HBV cirrhosis patients on long-term lamivudine therapy

In hepatitis B virus (HBV) cirrhosis patients on long-term lamivudine (LAM), the relationships between HBV suppression, development of viral resistance and disease outcome are unclear. We analysed the dynamic of serum HBV-DNA and its relationship with the clinical course of 59 patients (52 males, mean age 51.4 ±8.4 years, 12 HBeAg positive and 47 HBeAg negative, and 57 genotype D and two genotype A) with cirrhosis (45 in Child-Turcotte-Pugh class A) and high levels of serum HBV-DNA (median 14.7x107 genomes/ml) treated with LAM [median (range): 44 (15–78) months]. A total of 50 patients (84.7%) achieved a virological response (serum HBV-DNA negative by PCR) during the first 6 months of ther…

Point‐of‐care HCV RNA testing in the setting of DAA therapy: HCV‐FiS (HEpatitis C Virus Fingerstick Study)

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…

An Outbreak of Hepatitis C Virus Infection Among Transfused Thalassemia Patients: Root Cause Analysis, Phylogenetic Epidemiology and Antiviral Therapy

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…

Binding of flunitrazepam to differentiating neurons cultured in a chemically defined, hormone-supplemented medium

[3H]Flunitrazepam (FNZ) binding to cortical neurons from fetal rat brain was investigated in vitro. The use of a synthetic medium specific for neurons made it possible to plot a developmental curve of3H-FNZ binding in an almost pure neuronal culture. Detectable specific binding was present in vitro at time 0 (that is, the 16th gestational day). A progressive increase of binding, due to an increment in the number of recognition sites, was observed on the subsequent days. The affinity of the specific binding sites to3H-FNZ was enhanced by the addition of exogenous GABA, whereas the density was not affected. © 1990 Plenum Publishing Corporation.

Liver disease in chelated transfusion-dependent thalassemics: the role of iron overload and chronic hepatitis C.

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…

A rs4374383 Single Nucleotide Polymorphisms of MERTK gene is linked to a higher likelihood of hepatocellular carcinoma in patients with HCV cirrhosis

Fibrosis evaluation by transient elastography in patients with long-term sustained HCV clearance.

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…

Different doses of consensus interferon plus ribavirin in patients with hepatitis C virus genotype 1 relapsed after interferon monotherapy: a randomized controlled trial.

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)…

Epidemiologia molecolare dell'infezione da HCV in un Comune Siciliano

The impact of sustained virological response on clinical outcomes in compensated HCV cirrhosis: a prospective cohort study

HCV CLEARANCE AFTER PEG IFN PLUS RBV IMPROVES THE COURSE OF HCV CIRRHOSIS REGARDLESS OF PORTAL HYPERTENSION

Endemic hepatitis C virus infection in a Sicilian town: Further evidence for iatrogenic transmission

The prevalence of and risk factors for HCV and HBV infections in the general population and the predictive value of ALT screening in identifying anti-HCV positive subjects have been evaluated in a small Sicilian town. A random 1:4 sampling from the census of the general population was performed. Anti-HCV, HCV-RNA, HCV genotype, HBsAg, and anti-HBc were tested. The linkage between HCV infection and potential risk factors was evaluated by multiple logistic regression analysis. Among 721 subjects studied, 75 (10.4%) were anti-HCV positive. The HCV infection rate increased from 0.4% in subjects 10–29 years of age to 34% in those > 60 years of age. Among the 75 anti-HCV positive subjects, 66.7% …

HBV reactivation in patients with HCV/HBV cirrhosis on treatment with direct-acting antivirals

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…

Evaluation of the diagnostic performances of two commercially available assays for the detection of enteric adenovirus antigens

The performance of 2 antigenic commercial assays for enteric adenovirus (AdV) infection, bioNexia Rota-Adeno ImmunoChromatographic Tests (ICT) and LIAISON® Adenovirus ChemiLuminescence Immuno Assays (CLIA), was evaluated on 321 stools from children hospitalized for acute gastroenteritis in Palermo, Italy, using a Real time-PCR (Rt-PCR) as reference method. The CLIA showed higher sensitivity (77% vs 60%), accuracy (94.4 vs 90.9) and concordance (k: 0.81 vs 0.67) with respect to ICT, despite equivalent specificity (98.8%). Using the Ct values of the Rt-PCR as a proxy of the fecal viral load, similar Ct values (mean 9.32 vs 9.89) were observed among the true positive samples, whilst a signific…

150 LIVER RELATED EVENTS AND SURVIVAL IN PATIENTS WITH COMPENSATED HCV CIRRHOSIS: THE ROLE OF SUSTAINED VIROLOGICAL RESPONSE TO PEG-IFN BASED THERAPY AND PORTAL HYPERTENSION

Rat CNS cell culture. Enhancement of neuronal survival and delay of glial proliferation by serum from patients with multiple sclerosis. A morphological study.

The addition of serum from multiple sclerosis (MS) patients to the culture medium of dissociated cells from cerebral hemispheres of rat embryos caused a delay in glial proliferation and an enhancement of neuronal survival. Sera from normal individuals and patients with other neurological diseases failed to show this effect. These morphological observations are interpreted as the outcome of inhibition of in vitro gliogenesis.

Inhibition of glial proliferation in vitro by serum from patients with multiple sclerosis

Primary cell cultures from fetal rat CNS have been employed to evaluate the effects caused by the addition of serum from patients affected by multiple sclerosis (MS). MS-serum supplemented media caused a decrease in [3H]-thymidine incorporation into the cultures, thus indicating an inhibitory effect on proliferating glial cells. Sera from patients in remission stage of the disease showed an inhibitory effect not significatively lower than those from patients in acute stage. These results suggest that glial cells may be a target of circulating factors present in MS.

RIATTIVAZIONE DELL’INFEZIONE OCCULTA DA HBV NEL PAZIENTE IMMUNOCOMPROMESSO: STUDIO DELLA ETEROGENEITÀ VIRALE

VALUTAZIONE DELLA CLEARANCE DI HCV-RNA SOTTO TRATTAMENTO ANTIVIRALE CON TRANSCRIPTION-MEDIATED AMPLIFICATION (TMA)

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Virus-related insulin resistance in HCV genotype 1 chronic hepatitis C : a major disease modifier

Neutralizing Antibodies Response against SARS-CoV-2 Variants of Concern Elicited by Prior Infection or mRNA BNT162b2 Vaccination.

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+ an…

Characterization of measles virus strains circulating in Southern Italy (Palermo area, Sicily) between 2010 and 2011

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 M…

Triiodothyronine-Induced Shortening of Chromatin Repeat Length in Neurons Cultured in a Chemically Denned Medium

Abstract: At the time of terminal differentiation, mammalian cortical neurons undergo a dramatic change in the structural organization of their chromatin: the nucleosomal repeat length shortens from ∼200 base pairs in fetuses to a value of 165 base pairs after birth. These events occur several days after the end of neuronal proliferation. Previously, we reported that rat cortical neurons cultured in a very selective synthetic medium were not yet programmed to these events at the end of mitotic cycles. Herein, we report that addition of triiodothyronine to neuronal cultures induces a shortening of the chromatin repeat length comparable to the natural one. Copyright © 1987, Wiley Blackwell. A…

Variability of reverse transcriptase and overlapping S gene in hepatitis B virus isolates from untreated and lamivudine-resistant chronic hepatitis B patients

Background The high degree of diversity of the hepatitis B virus (HBV) quasispecies in chronically infected individuals raises the possibility that HBV genetic variants favouring resistance to nucleoside/nucleotide analogues (NAs) might pre-exist to treatment. The aim of this study was to investigate the genetic variability of the entire HBV reverse transcriptase (RT) domain and of the overlapping S gene in a large series of untreated hepatitis B surface antigen carriers and in lamivudine (3TC)-resistant patients. Methods Sequencing analysis of the entire HBV RT domain of isolates from 100 untreated (treatment- naive group) and 59 3TC-resistant (3TC-resistant group) consecutive patients wit…

VARIABILITY OF THE HBV POL GENE REVERSE-TRANSCRIPTASE DOMAIN IN VIRAL ISOLATES FROM UNTREATED AND LAMIVUDINE-RESISTANT CHRONIC HEPATITIS B PATIENTS

RUOLO DELL’INFEZIONE OCCULTA DA HBV NEL PAZIENTE IMMUNOCOMPROMESSO

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Combined treatment of relapse of chronic hepatitis C with high-dose α2b interferon plus ribavirin for 6 or 12 months

Abstract Background/Aims: Retreatment of relapses of chronic hepatitis C with a standard regimen of interferon plus ribavirin for 6 months obtains a sustained response in a minority of patients with high viraemia and genotype 1b . We aimed to assess whether increasing the interferon dose and prolonging the time of combined treatment may enhance the effectiveness, and also to evaluate the tolerability, and to identify the determinants of sustained response. Methods: Fifty subjects with chronic hepatitis C who had relapsed after one or more courses of α-interferon monotherapy were randomised to receive α 2 b interferon (6 MU tiw) plus ribavirin (1000–1200 mg daily) for 6 or 12 months. ALT nor…

Vitamin D levels and IL28B polymorphisms are related to rapid virological response to standard of care in genotype 1 chronic hepatitis C.

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…

Anti-hepatitis A virus seroprevalence and seroconversion in a cohort of patients with chronic viral hepatitis

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 …

Hepatitis B Virus Reactivation and Alemtuzumab Therapy.

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. Lam…

Are hepatitis G virus and TT virus involved in cryptogenic chronic liver disease?

Abstract Background . Hepatitis G virus can cause chronic infection in man but the role of this agent in chronic liver disease is poorly understood. Little is known about the relation of another newly discovered agent, the TT virus, with chronic liver disease. Aim . To investigate the rate of infection with hepatitis G virus and TT virus in patients with cryptogenic chronic liver disease. Patients . A total of 23 subjects with chronically raised alanine transaminase and a liver biopsy in whom all known causes of liver disease had been excluded, and 4D subjects with hepatitis C virus-related chronic liver disease. Methods . Evaluation of anti-hepatitis G virus by enzyme immunoassay. Hepatiti…

Peg-interferon alone or combined with ribavirin in HCV cirrhosis with portal hypertension:a randomized controlled trial

Abstract BACKGROUND/AIMS: Risks and benefits of antiviral therapy in HCV cirrhosis with portal hypertension are poorly known. METHODS: We performed a randomized controlled trial in 102 HCV patients with compensated cirrhosis and portal hypertension: 51 received 1 microg/kg/week of Pegylated-interferon alpha-2b and 51 Pegylated-interferon plus 800 mg/day of ribavirin up to 52 weeks. RESULTS: By intention-to-treat analysis, five patients on monotherapy and eleven on combination therapy achieved a sustained virological response (9.8% vs. 21.6%, p=0.06). The response was more frequent for genotypes 2 or 3 than genotype 1 (66.6% vs. 11.3%, p=0.001). Genotype 1, who had low viral load at start of…

Rat CNS neurons are not yet programmed to shorten their chromatin repeat length at the end of fetal neurogenesis.

Neurons from rat fetal cerebral hemispheres were grown in a synthetic medium (Maat medium), as previously described, for different periods of time. The repeat length of their chromatin was determined by micrococcal nuclease digestion and compared with that of neurons isolated from postnatal rat brain of corresponding ages. In contrast to the in vivo situation, we found that neurons, dissociated at the 16th gestational day and cultured in vitro, did not undergo the shortening of their chromatin repeat, thus indicating that, at the end of their mitotic cycles, they are not yet programmed to this event. © 1986.

Antibodies Responses to SARS-CoV-2 in a Large Cohort of Vaccinated Subjects and Seropositive Patients

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 &gt

Evaluating the risk of hepatitis B reactivation in patients with haematological malignancies: is the serum hepatitis B virus profile reliable?

Background/Aim: Patients with an occult hepatitis B virus (HBV) infection undergoing deep immunosuppression are potentially at risk of HBV reactivation. In order to assess whether a polymerase chain reaction (PCR) assay for HBV DNA in serum could be used to predict the reactivation of an occult HBV infection, we performed a retrospective study in a cohort of Sicilian patients with oncohaematological diseases. Methods: We studied by a highly sensitive ad hoc nested PCR for serum HBV DNA 75 HBsAg-negative oncohaematological patients requiring chemotherapy. Results: Thirty-three patients (44%) were HBV seronegative (anti-HBc and anti-HBs negative) and 42 patients (56%) were HBV seropositive (a…

Distribution of VP7 serotypes and VP4 genotypes among rotavirus strains recovered from Italian children with diarrhea

108 rotavirus strains obtained from children with diarrhea hospitalized in Palermo, Italy, in the years 1990-1994, were examined by seminested PCR to study the relative frequency and distribution of the four most common alleles of the gene 4. Such strains were selected from 344 human rotavirus strains recovered in palermo during those years after characterization by electropherotyping, subgrouping and G serotyping. One hundred and seven of the 108 strains could be classified into P types, the P[8], G1 (38.3%) and the P[8], G4 (52.3%) types being predominant. The unique strain whose P genotype could not be identified showed an unusual combination of long migration electrophoretic pattern and…

Differing kinetics of anti-spike protein IgGs and neutralizing antibodies against SARS-CoV-2 after Comirnaty (BNT162b2) immunization

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 diff…

Cinetica della risposta virologica e della comparsa di mutanti virali in pazienti con malattia cronica di fegato HBV-correlatain terapia con adefovir

413 Bayesian coalescent inference of hepatitis C virus introduction from molecular sequences: The camporeale model

IL-10 and TNF-α polymorphisms and the recovery from HCV infection

Hepatitis C virus (HCV) infection becomes chronic in about 85% of infected individuals, whereas only 15% of infected people clear spontaneously the virus. It is conceivable that the host immunogenetic background influences the course of infection in term of recovery. Thus, in this study we have evaluated the effect of functionally relevant polymorphisms at tumor necrosis factor-alpha (TNF-alpha, i.e., 2 biallelic polymorphisms at nt -863 and nt-308 of the promoter) and interleukin-10 (IL-10) loci (i.e., 1 biallelic polymorphism at nt -1082 of the promoter), on the clearance of HCV infection. To this purpose, we compared 18 Sicilian patients who had spontaneously recovered from previous HCV …

Effects of Eradicating Hepatitis C Virus Infection in Patients With Cirrhosis Differ With Stage of Portal Hypertension.

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 hepatoc…

PEG-INTERFERON PLUS RIBAVIRIN IN COMPENSATED HCV CIRRHOSIS WITH PORTAL HYPERTENSION: THE ROLE OF RAPID AND EARLY VIROLOGICAL RESPONSE IN PREDICTING THE SUSTAINED VIROLOGICAL RESPONSE

Phylogenetic Analysis of isolates from new cases of HBV infection in Southern Italy.

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 …

Response-adjusted α-interferon therapy for chronic hepatitis C in HIV-infected patients

Abstract In patients with chronic hepatitis C and HIV infection, responsiveness to the standard schedule of α-interferon (IFN) is unsatisfactory. To quantify the effectiveness of tailoring IFN dosage according to HCV viral load under treatment, we enrolled 41 patients (M/F 32/9) chronically coinfected by HCV and HIV with chronic liver disease. All were former i.v. drug addicts, with a mean age of 32±4 years, and had clinical and histological evidence of chronic hepatitis (10% with cirrhosis). The CDC stage was A1 in five, A2 in 14, A3 in eight, B2 in eight, B3 in three and C3 in three. Twenty four patients were on triple therapy with protease inhibitors, 11 were on two-drug anti-HIV regimen…

Efficacy of 8 weeks elbasvir/grazoprevir regimen for naïve-genotype 1b, HCV infected patients with or without glucose abnormalities: Results of the EGG18 study.

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®&lt; 9.0 kPa). Viral load(VL) has been evaluated by Roche TaqMan RT-PCR(LLOQ &lt; 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 &gt; …

Detection of enteric adenoviruses 40 and 41 in stool specimens by monoclonal antibody-based enzyme immunoassays

To examine the role of enteric adenoviruses (Ad40 and Ad41) in children with acute gastroenteritis, we evaluated 273 children with diarrhoea and 137 without enteric symptoms in Palermo, Italy, during an 8-month period. Stools were tested by two home-made monoclonal-based ELISAs to detected genus-specific adenovirus antigen and to type Ad40 and Ad41. Twenty-five samples (6.1%) were found to contain adenovirus, 18 of which were grown in Graham 293 and in HEp-2 cells. Ad40 and Ad41 were detected in 2.6% of children with diarrhoea and in none in the control group, while non-enteric adenoviruses were obtained from both patients (3.2%) and controls (6.5%). Samples containing Ad40 and Ad41 were po…

The risk of hepatocellular carcinoma in HBV cirrhosis is affected by polymorphisms of the MERTK gene

Genotyping of Legionella pneumophila serogroup 1 strains isolated in Northern Sicily, Italy.

During a three-year period, from April 2002 to May 2005, one hundred-forty-seven samples, taken from technical systems of water distribution at point of use, were repeatedly collected at six different sites in Northern Sicily and assayed for the presence of Legionella pneumophila serogroup 1 and serogroups 2 to 14. At the first samplings, the water distribution systems of all the sites were heavily contaminated, and disinfection treatments by the superheat and flush method were therefore performed. Treatments were always successful against L. pneumophila sg.1, but only in a few cases against all other serogroups. Eighty-six strains of L. pneumophila sg. 1, isolated from 26 of these samples,…

Assessment of hepatitis C virus-RNA clearance under combination therapy for hepatitis C virus genotype 1: performance of transcription-mediated amplification assay

Monitoring of HCV-RNA in blood during antiviral therapy is performed mostly by commercially available reverse transcription polymerase chain reaction-based (RT-PCR) assays, with a lower detection limit of 30-50 IU/mL of HCV-RNA. Use of different tests in the pivotal trials of combination therapy has generated some discordance, in terms of predictive value of the early virological response (EVR). To evaluate whether the use of a more sensitive test, as a qualitative assay based on transcription mediated amplification (TMA) with a lower detection limit of 5-10 IU/mL of HCV-RNA, may obtain a better prediction of EVR and of the ultimate virological outcome, we retrospectively evaluated serial s…

Phylogenetic reconstruction of HCV genotype 1b dissemination in a small city centre: The Camporeale model

Several seroepidemiological population-based surveys carried out in Italy have shown a high prevalence of hepatitis C virus (HCV) infection. Camporeale (CP), a small Sicilian town with a 10.4% prevalence of HCV mostly genotype 1b, probably represents a specific context, since intravenous drug addiction, and sexual promiscuity are almost absent. In order to reconstruct the pattern of introduction and diffusion of HCV in this ecological niche, the NS5 genomic region of 72 HCV genotype 1 isolates (39 from CP and 33 collected throughout Sicily) was amplified and sequenced. Sequences were aligned and analyzed by BioEdit, PAUP and BEAST, and their molecular evolution compared. Thirty-eight HCV ge…

Impact of HBV genotypes A and D genetic variability on infection evolution

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 phy…

Phylogenetic analysis in the clinical risk management of an outbreak of hepatitis C virus infection among transfused thalassaemia patients in Italy

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…

Age and Cytokine Gene Variants Modulate the Immunogenicity and Protective Effect of SARS-CoV-2 mRNA-Based Vaccination

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 genotyp…

Vitamin D levels and IL28B polymorphisms are related to rapid virological response to standard of care in genotype 1 chronic hepatitis C.

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 p…

HCV genotypes in western Sicily: any evidence for a shift?

Background: The relative prevalence of each HCV strain in a specific country is characterized by a predominant genotype and a number of other sub-prevalent types. Over the last decade a shift away from the prevalent HCV G1 towards G3 and G4 has been reported in some countries, and might affect the global management of HCV disease. Aim: In order to assess any possible variation in the prevalence of HCV genotypes in Sicily, we surveyed an hospital based cohort of subjects with chronic HCV infection observed over the last ten years. Patient and methods: 3209 Italian patients resident in Western Sicily, 1842/1367 M/F, between 1 and 89 years of age, presented at our tertiary referral Laboratory …

PEG_interferon plus Ribavirin in compensated HCV cirrhosis with portal hypertension: the role of rapid and early virological response in predicting the sustained virological response

Triiodothyronine accelerates the synthesis of synapsin I in developing neurons from fetal rat brain cultured in a synthetic medium.

The effect of Triiodothyronine (T3) on Synapsin I appearance in rat cortical neurons has been investigated in vitro. Neuronal cultures from 16-day-old fetal rat brain grown in the absence of T3, express immunohystochemically detectable Synapsin I at the 14th day in vitro. The addition of the hormone to the culture medium determines an early (at the 7th day in vitro) appearance of fluorescent dots specific for Synapsin I. © 1990 Plenum Publishing Corporation.

HCV-1b intra-subtype variability: Impact on genetic barrier to protease inhibitors

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 t…

Infezione occulta da HBV in pazienti con malattie linfoproliferative in trattamento chemioterapico

HBsAg quantification in HBeAg negative cirrhosis on nucleoside/nucleotide analogue (NA) and risk of development of HCC

The impact of sustained virological response on clinical outcome in compensated HCV cirrhosis: a prospective cohort study

Hepatic steatosis and insulin resistance are associated with severe fibrosis in patients with chronic hepatitis caused by HBV or HCV infection.

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 def…

INFEZIONE OCCULTA DA HBV NEL PAZIENTE IMMUNOCOMPROMESSO: STUDIO DELLA ETEROGENEITA’ VIRALE

Viral Sequence Analysis of Occult HBV Infection and Its Reactivation in Immunosuppressed Patients

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 diversit…

The impact of insulin resistance, serum adipocytokines and visceral obesity on steatosis and fibrosis in patients with chronic hepatitis C

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 obe…

Selective culture of rat CNS neurons in a synthetic medium.

A Chemically Defined Medium is described which facilitates the survival of neurons in primary cultures of rat cerebral hemispheres. More than 90% of all cells were identified as neurons using neurofilament as a marker in an immunocytochemical assay. In contrast, serum-supplemented medium, by stimulating nonneuronal cell proliferation, hinders the survival of neurons in culture.

HVR-1 quasispecies modifications occur early and are correlated to initial but not sustained response in HCV-infected patients treated with pegylated- or standard-interferon and ribavirin

Abstract Background/Aims HVR-1 quasispecies composition and evolution were investigated in patients chronically infected with genotype 1b HCV, treated with PEG-IFN α2b or STD-IFN α2b plus RBV. Methods HVR-1 heterogeneity was assessed by calculating nucleotidic complexity, diversity, synonymous (S) and non-synonymous (NS) substitutions at baseline, after 4 weeks of therapy ( T 1) and at follow-up ( T 18). Evolution of viral quasispecies was analysed by constructing phylogenetic trees. Results No correlation of baseline viremia with heterogeneity was observed. Nucleotidic complexity was lower in patients showing early virological response, and tended to be inversely correlated to viral load d…

Detection of IgM antibodies specific for measles virus by capture and indirect enzyme immunoassays.

Summary During a measles outbreak, 112 serum specimens from 88 hospitalized patients were received in our laboratory for investigation of a morbilliform rash. These specimens (88 acute- and 24 convalescent-phase) were tested for the presence of measles-specific IgM antibodies by a capture EIA (enzyme immunoassay) using peroxidase-conjugated measles virus antigens and by an indirect EIA. Commercially available indirect EIA kits for measles-specific IgM antibodies were also used and compared with our homemade EIAs. Specificity studies included a collection of serum specimens containing rheumatoid factor, antinuclear antibodies or IgM antibodies specific to other viruses, and sera from blood d…

Antibodies Responses to SARS-CoV-2 in a Large Cohort of Vaccinated Subjects and Seropositive Patients

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% vaccinat…

Phylodynamic Analysis and Implication of HCV Genotype 4 Variability on Antiviral Drug Response and T-Cell Recognition.

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 na&iuml

ISDR pattern and evolution in patients with chronic hepatitis C treated with standard or Peg-IFN plus ribavirin

The aim of the study was to characterize the interferon sensitivity determining region (ISDR) mutation pattern and its changes at 4 weeks of treatment in a population of patients infected with hepatitis C virus (HCV) genotype 1b receiving standard or PEG-IFN plus ribavirin (RBV), to find possible early correlates of therapy outcome.Forty-five patients with chronic hepatitis due to HCV 1b were treated by PEG-IFN-α2b (n=23) or IFN-α2b (n=22) plus RBV 1000–1200 mg/day. They were classified 24 weeks after stopping therapy as sustained responders (SR), relapsers (REL) or non-responders (NR). Sixteen patients were SR, 12 REL and 17 NR. ISDR mutations were evaluated by direct sequencing at baselin…

HCV genotypes in Sicily: is there any evidence of a shift?

The distribution of HCV strains in any area is characterized by a relative prevalence of one genotype, and a number of less prevalent types. In some Western countries a change from the prevalent HCV genotype 1 to genotypes 3 and 4 has been reported in the last decade. In order to assess possible variations of the distribution of HCV genotypes in Sicily, a southern region of Italy, a hospital-based cohort, collected prospectively, of 3,209 subjects with chronic HCV infection was surveyed, comparing the distribution of HCV genotypes during two consecutive periods, from 1997 to 2002 and from 2003 to 2007, according to age and gender. The results show that genotype 1b, which has been historical…

Rs4374383 single nucleotide polymorphism of MERTK gene influences the development of hepatocellular carcinoma (HCC) in patients with HCV cirrhosis

Schistosomiasis and antiviral treatment of chronic hepatitis C

Bayesian coalescent inference of hepatitis C virus introduction from molecular sequences: the Camporeale model

Riattivazione dell'infezione occulta da HBV nel paziente immunocompromesso:studio dell'eterogeneità virale

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

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…

The impact of insulin resistance, serum adipocytokines and visceral obesity on steatosis and fibrosis in patients with chronic hepatitis C.

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 ‘naı¨ve’ patients with chronic hepatitis C, before, during and after therapy with Peg-Interferon-alpha 2a plus Ribavirin. Results Forty-eightpatientswereincluded(M/F28/20;meanage50.0 12.6years; 62.5% genotype-1). Body mass index was 26.4 4.0 kg/m2 , and visceral obesity was present in 24…

Valutazione della clearance di HCV-RNA sotto trattamentio antivirale con Transcription-Mediated Amplification (TMA)

Monkeypox proctitis treated with doxycycline in an HIV MSM returning to Italy from France

No abstract available

Infezione occulta da HBV nel paziente immunocompromesso.studio dell'eterogeneità virale

High rate of spontaneous viral clearance in patients with iatrogenic acute hepatitis C

Hepatic steatosis and insulin resistance are associated with severe fibrosis in patients with chronic hepatitis caused by HBV or HCV infection

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 def…

Non-invasive assessment of the liver fibrosis by transient elastography (TE) in patients with transfusion-dependent thalassemia

High-dose prolonged combination therapy in non-responders to interferon monotherapy for chronic hepatitis C

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 sustain…

Identification of picobirnavirus from faeces of Italian children suffering from acute diarrhea

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.