"Real world" efficacy of bulevirtide in HBV/HDV-related cirrhosis including people living with HIV: Results from the compassionate use programme at INMI Spallanzani in Rome, Italy.

OBJECTIVES: We describe the preliminary results of bulevirtide compassionate use in patients with hepatitis B and delta virus (HBV/HDV)-related cirrhosis and clinically significant portal hypertension, including those living with HIV. METHODS: We conducted a prospective observational study of consecutive patients. Clinical evaluation, liver function tests, bile acid levels, HDV-RNA, HBV-DNA, hepatitis B surface antigen, and liver and spleen stiffness were assessed at baseline and after treatment months 1, 2, 3, 4, 6, 9, and 12. HIV-RNA and CD4+/CD8+ count were assessed in people living with HIV. The first drug injection was administered under nurse supervision, and counselling was provided and adherence reviewed at each visit. RESULTS: In total, 13 patients (61.5% migrants) were enrolled. The median treatment duration was 11 months. At month 6, mean alanine aminotransferase (ALT) levels fell by 64.5% and mean liver and spleen stiffness decreased by 8.6 and 0.9 kPa, respectively. The mean baseline HDV-RNA was 3.34 log IU/mL and 5.10 log IU/mL in people without and with HIV (n = 5) (p = 0.28), respectively. A similar mean decline was observed in both groups: -2.06 log IU/mL and -1.93 log IU/mL, respectively (p = 0.87). A combined response (undetectable HDV RNA or ≥ -2 log IU/mL decline vs. baseline, with ALT normalization) was achieved in 66% of subjects without and in 60% of patients with HIV. Patients with HIV showed persistently undetectable HIV-RNA and a progressive increase in CD4+/CD8+ cells during treatment. No patient discontinued bulevirtide because of adverse effects. CONCLUSIONS: Preliminary results suggest that bulevirtide is feasible and well-tolerated in populations with difficult-to-treat conditions, such as those with HIV/HBV/HDV co-infection and migrants, when special attention is given to patient education. HDV-RNA decline during treatment was similar in people living with and without HIV.

Evolution of SARS-CoV-2 variants of concern over a period of Delta and Omicron cocirculation, among patients hospitalized for COVID-19 in an Italian reference hospital: Impact on clinical outcomes.

Despite the higher transmissibility of Omicron Variant of Concern (VOC), several reports have suggested lower risk for hospitalization and severe outcomes compared to previous variants of SARS-CoV-2. This study, enrolling all COVID-19 adults admitted to a reference hospital who underwent both the S-gene-target-failure test and VOC identification by Sanger sequencing, aimed to describe the evolving prevalence of Delta and Omicron variants and to compare the main in-hospital outcomes of severity, during a trimester (December 2021 to March 2022) of VOCs' cocirculation. Factors associated with clinical progression to noninvasive ventilation (NIV)/mechanical ventilation (MV)/death within 10 days and to MV/admission to intensive care unit (ICU)/death within 28 days, were investigated through multivariable logistic regressions. Overall, VOCs were: Delta n = 130/428, Omicron n = 298/428 (sublineages BA.1 n = 275 and BA.2 n = 23). Until mid-February, Delta predominance shifted to BA.1, which was gradually displaced by BA.2 until mid-March. Participants with Omicron VOC were more likely to be older, fully vaccinated, with multiple comorbidities and to have a shorter time from symptoms' onset, and less likely to have systemic symptoms and respiratory complications. Although the need of NIV within 10 days and MV within 28 days from hospitalization and the admission to ICU were less frequent for patients with Omicron compared to those with Delta infections, mortality was similar between the two VOCs. In the adjusted analysis, multiple comorbidities and a longer time from symptoms' onset predicted 10-day clinical progression, while complete vaccination halved the risk. Multimorbidity was the only risk factor associated with 28-day clinical progression. In our population, in the first trimester of 2022, Omicron rapidly displaced Delta in COVID-19 hospitalized adults. Clinical profile and presentation differed between the two VOCs and, although Omicron infections showed a less severe clinical picture, no substantial differences for clinical progression were found. This finding suggests that any hospitalization, especially in more vulnerable individuals, may be at risk for severe progression, which is more related to the underlying frailty of patients than to the intrinsic severity of the viral variant.

Longitudinal characterisation of B and T-cell immune responses after the booster dose of COVID-19 mRNA-vaccine in people with multiple sclerosis using different disease-modifying therapies.

BACKGROUND: The decline of humoral response to COVID-19 vaccine led to authorise a booster dose. Here, we characterised the kinetics of B-cell and T-cell immune responses in patients with multiple sclerosis (PwMS) after the booster dose. METHODS: We enrolled 22 PwMS and 40 healthcare workers (HCWs) after 4-6 weeks from the booster dose (T3). Thirty HCWs and 19 PwMS were also recruited 6 months (T2) after the first dose. Antibody response was measured by anti-receptor-binding domain (RBD)-IgG detection, cell-mediated response by an interferon (IFN)-γ release assay (IGRA), Th1 cytokines and T-cell memory profile by flow cytometry. RESULTS: Booster dose increased anti-RBD-IgG titers in fingolimod-treated, cladribine-treated and IFN-ß-treated patients, but not in ocrelizumab-treated patients, although antibody titres were lower than HCWs. A higher number of fingolimod-treated patients seroconverted at T3. Differently, T-cell response evaluated by IGRA remained stable in PwMS independently of therapy. Spike-specific Th1-cytokine response was mainly CD4+ T-cell-mediated, and in PwMS was significantly reduced (p<0.0001) with impaired IL-2 production compared with HCWs at T3. In PwMS, total Th1 and IFN-γ CD4+ T-cell responders to spike protein were increased from T2 to T3.Compared with HCWs, PwMS presented a higher frequency of CD4+ and CD8+ terminally differentiated effector memory cells and of CD4+ effector memory (TEM) cells, independently of the stimulus suggesting the association of this phenotype with MS status. CD4+ and CD8+ TEM cell frequency was further increased at T3 compared with T2. CONCLUSIONS: COVID-19 vaccine booster strengthens humoral and Th1-cell responses and increases TEM cells in PwMS.

Hepatitis B Virus and microRNAs: A Bioinformatics Approach.

In recent decades, microRNAs (miRNAs) have emerged as key regulators of gene expression, and the identification of viral miRNAs (v-miRNAs) within some viruses, including hepatitis B virus (HBV), has attracted significant attention. HBV infections often progress to chronic states (CHB) and may induce fibrosis/cirrhosis and hepatocellular carcinoma (HCC). The presence of HBV can dysregulate host miRNA expression, influencing several biological pathways, such as apoptosis, innate and immune response, viral replication, and pathogenesis. Consequently, miRNAs are considered a promising biomarker for diagnostic, prognostic, and treatment response. The dynamics of miRNAs during HBV infection are multifaceted, influenced by host variability and miRNA interactions. Given the ability of miRNAs to target multiple messenger RNA (mRNA), understanding the viral-host (human) interplay is complex but essential to develop novel clinical applications. Therefore, bioinformatics can help to analyze, identify, and interpret a vast amount of miRNA data. This review explores the bioinformatics tools available for viral and host miRNA research. Moreover, we introduce a brief overview focusing on the role of miRNAs during HBV infection. In this way, this review aims to help the selection of the most appropriate bioinformatics tools based on requirements and research goals.

Comparison of SARS-CoV-2 Detection in Nasopharyngeal Swab and Saliva Samples from Patients Infected with Omicron Variant.

To compare the detection of the SARS-CoV-2 Omicron variant in nasopharyngeal-swab (NPS) and oral saliva samples. 255 samples were obtained from 85 Omicron-infected patients. SARS-CoV-2 load was measured in the NPS and saliva samples by using Simplexa™ COVID-19 direct and Alinity m SARS-CoV-2 AMP assays. Results obtained with the two diagnostic platforms showed very good inter-assay concordance (91.4 and 82.4% for saliva and NPS samples, respectively) and a significant correlation among cycle threshold (Ct) values. Both platforms revealed a highly significant correlation among Ct obtained in the two matrices. Although the median Ct value was lower in NPS than in saliva samples, the Ct drop was comparable in size for both types of samples after 7 days of antiviral treatment of the Omicron-infected patients. Our result demonstrates that the detection of the SARS-CoV-2 Omicron variant is not influenced by the type of sample used for PCR analysis, and that saliva can be used as an alternative specimen for detection and follow-up of Omicron-infected patients.

Dynamic Evolution of Humoral and T-Cell Specific Immune Response to COVID-19 mRNA Vaccine in Patients with Multiple Sclerosis Followed until the Booster Dose.

This study characterizes antibody and T-cell immune responses over time until the booster dose of COronaVIrus Disease 2019 (COVID-19) vaccines in patients with multiple sclerosis (PwMS) undergoing different disease-modifying treatments (DMTs). We prospectively enrolled 134 PwMS and 99 health care workers (HCWs) having completed the two-dose schedule of a COVID-19 mRNA vaccine within the last 2-4 weeks (T0) and followed them 24 weeks after the first dose (T1) and 4-6 weeks after the booster (T2). PwMS presented a significant reduction in the seroconversion rate and anti-receptor-binding domain (RBD)-Immunoglobulin (IgG) titers from T0 to T1 (p < 0.0001) and a significant increase from T1 to T2 (p < 0.0001). The booster dose in PwMS showed a good improvement in the serologic response, even greater than HCWs, as it promoted a significant five-fold increase of anti-RBD-IgG titers compared with T0 (p < 0.0001). Similarly, the T-cell response showed a significant 1.5- and 3.8-fold increase in PwMS at T2 compared with T0 (p = 0.013) and T1 (p < 0.0001), respectively, without significant modulation in the number of responders. Regardless of the time elapsed since vaccination, most ocrelizumab- (77.3%) and fingolimod-treated patients (93.3%) showed only a T-cell-specific or humoral-specific response, respectively. The booster dose reinforces humoral- and cell-mediated-specific immune responses and highlights specific DMT-induced immune frailties, suggesting the need for specifically tailored strategies for immune-compromised patients to provide primary prophylaxis, early SARS-CoV-2 detection and the timely management of COVID-19 antiviral treatments.

Epidemiological, clinical and virological characteristics of four cases of monkeypox support transmission through sexual contact, Italy, May 2022.

Since May 2022, an outbreak of monkeypox has been ongoing in non-endemic countries. We report four cases in Italy in young adult men reporting condomless sexual intercourse. The patients are in good clinical condition with no need for specific antiviral drugs. Biological samples from seminal fluid were positive for monkeypox viral DNA. For many other viruses found in semen there is no evidence of sexual transmission. The possibility of sexual transmission of monkeypox virus needs to be investigated.

Alpha, Beta, gamma human PapillomaViruses (HPV) detection with a different sets of primers in oropharyngeal swabs, anal and cervical samples.

BACKGROUND: Recent studies have shown a 13-fold increase of oropharyngeal cancer in the presence of HPV, while α-HPV detection seems to be rare in oral cavity in comparison to anal or cervical district, many novel ß and γ types have been isolated in this anatomical site suggesting a wide tropism range. Currently, there are no guidelines recommending HPV oral cavity screening as a mandatory test, and it remains unknown which HPV types should be included in HPV screening programs. Our goal was to assess HPV prevalence in oropharyngeal, anal, and cervical swabs using different sets of primers,which are able to amplify α, ß, γ HPV types. METHODS: We analysed the presence of HPV DNA in oropharyngeal (n = 124), anal (n = 186), cervical specimens (n = 43) from HIV positive and negative patients using FAP59/64 and MY09/11 primers. All untyped strains were genetically characterized through PCR amplification and direct sequencing of partial L1 region, and the resulting sequences were classified through phylogenetic analysis. RESULTS: HPV prevalence was 20.9% in 124 oropharyngeal swab samples, including infections with multiple HPV types (5.6%). HPV prevalence in this anatomical site was significantly associated with serostatus: 63.3%in HIV positive and 36.3% in HIV negative patients (p < 0.05). Unclassified types were detected in 6 specimens. In our analysis, we did not observe any difference in HPV (α, ß, γ) prevalence between men and women. Overall, ß species were the most frequently detected 69.7%. When using anal swabs, for HIV positive patients, ß genus prevalence was 1% and γ genus was 3.7% including 6 unclassified types. In cervical samples from 43 HIV positive women (18 HPV negative and 25 positive by MY09/11 PCR), only one sample was positivite for ß1 species (2.4%) using FAP primers. Six of the untyped strains clustered with sequences from species 7, 9, 10, 8,12 of γ genus. Four sequences remained unclassified. Finally, ß and γ HPV prevalence was significantly lower than their respective HPV prevalence as identified by the Luminex system in all anatomical sites that were analyzed in previous studies. CONCLUSION: This study provides new information about viral isolates present in oropharyngeal site and it will contribute to improve the monitoring of HPV infection.

Analysis of hepatitis B virus-mixed genotype infection by ultra deep pyrosequencing in Sudanese patients, 2015-2016.

PURPOSE: The frequency of detection of HBV co-infection with multiple HBV genotypes is influenced by the detection method; usually co-infections are detected by multiplex PCR or hybridization assays, and are rarely confirmed by sequencing and conventional cloning. The objective of this study was to confirm by ultra-deep pyrosequencing (UDPS) mixed HBV infections, previously detected by multiplex-nested PCR. METHODS: Sixteen samples from HBV co-infected Sudanese patients detected by multiplex-nested PCR, were amplified targeting the P/S region and sequenced by UDPS. RESULTS: The only genotypes identified using UDPS were D and E, while A, B, C and F genotypes, previously detected by multiplex-nested PCR, were not detected. Specifically, 10 samples were shown to be mono-infected (D or E); in 3 out of 10 mono-infected D patients, a subtype combination was observed: D1 + D7 in 2 cases and D2 + D6 in 1 case. The remaining 6 subjects were D + E co-infected (harboring different mixtures of D subtypes). CONCLUSIONS: Overall, UDPS is more effective than multiplex-nested PCR for identifying multiple HBV genotypes and subtypes infections.

Daclatasvir, sofosbuvir with or without ribavirin for 24 weeks in hepatitis C genotype 3 cirrhosis: A real-life study.

INTRODUCTION AND AIM: Cirrhotic patients with hepatitis C virus genotype 3 infection show unsatisfactory outcomes after 12 weeks' treatment with direct antiviral agents. The National Italian Drug Agency allows 24 weeks of therapy in difficult-to-treat patients, including genotype 3 cirrhotics. Aim of this study was to evaluate efficacy and safety of a 24-week course of sofosbuvir plus daclatasvir±ribavirin in this population. MATERIALS AND METHODS: 106 consecutive cirrhotics (70.8% males, mean age 55.3±7.6 years) in 8 tertiary hepatology centers received sofosbuvir plus daclatasvir for 24 weeks. Ribavirin was administered in 85 (80.2%) based expected tolerability, at a mean dose of 964±202mg/day. Baseline Child-Pugh class was A 91.5%, B 6.6%, C 1.9%; mean baseline MELD was 8.5±2.7. RESULTS: All patients completed 12-week follow-up post-treatment, and 104 (98.1%) obtained sustained virological response (100% in ribavirin -treated patients vs. 90.4% without ribavirin; p=0.04). No worsening in renal and liver function was observed, no serious adverse events occurred. Two virological failures showed resistance associated variants (Y93H and S282T). CONCLUSION: An extended 24-week treatment with sofosbuvir plus daclatasvir+ribavirin obtained 100% efficacy in genotype 3 hepatitis C cirrhosis, with very limited side effects. The role of ribavirin seems crucial in this setting and should be administered if clinically feasible.

Early improvement of glycaemic control after virus clearance in patients with chronic hepatitis C and severe liver fibrosis: a cohort study.

HCV has been recognized as the cause of chronic hepatitis C (CHC) since 1990. CHC is associated with progressive liver damage and extrahepatic conditions. Direct antiviral agents (DAAs), approved in 2014, have shown effectiveness in eradicating HCV in most patients. However, little is known about the effect of viral eradication on hepatic and extra-hepatic damage. We performed a historical cohort study of patients with HCV-related liver diseases who achieved SVR from March 2015 to October 2016 at INMI Lazzaro Spallanzani liver Unit in Rome (Italy). Repeated measures of glycaemia were analysed through a multilevel analysis framework to assess short time kinetics of blood glucose level at different times after therapy and for different levels of HCV viremia. The analysis included 205 patients. A model assessing temporal kinetics and variation of glycaemia according to HCV viremia provided evidence that blood glucose levels significantly dropped in patients with diabetes achieving SVR. Most of the variations occurred at 3-5 weeks of therapy (-17.96 mg/dL; p<0.001) and in coincidence with HCV clearance (-13.92 mg/dL; p<0.001). A weak, non-statistically significant reduction was observed in normoglycemic patients. Our study provides evidence that DAAs therapy may significantly improve glycaemic control in patients with CHC achieving SVR even when liver diseases are already established.

Autochthonous acute hepatitis E: treatment with sofosbuvir and ribavirin.

INTRODUCTION: Hepatitis E virus (HEV) is an emerging cause of autochthonous-acute-hepatitis and acute-on-chronic-liver-failure in western countries. Treatment is not routinely used, despite ribavirin has a good antiviral effect. In vitro sofosbuvir inhibits HEV replication, but clinical data are lacking. CASE REPORT: We report a case of acute-on-chronic-liver-failure due to HEV treated with sofosbuvir and ribavirin. The treatment was capable of rapidly inducing both HCV and HEV viral suppression. CONCLUSION: In conclusion, although more data are required before firm conclusions could be drawn, the combination of sofosbuvir and ribavirin in not immunosuppressed patients with acute hepatitis E may be able to clear HEV infection.

Oral human Papillomavirus DNA detection in HIV-positive men: prevalence, predictors, and co-occurrence at anal site.

BACKGROUND: HIV-positive patients carry an increased risk of HPV infection and associated cancers. Therefore, prevalence and patterns of HPV infection at different anatomical sites, as well as theoretical protection of nonavalent vaccine should be investigated. Aim was to describe prevalence and predictors of oral HPV detection in HIV-positive men, with attention to nonavalent vaccine-targeted HPV types. Further, co-occurrence of HPV DNA at oral cavity and at anal site was assessed. METHODS: This cross-sectional, clinic-based study included 305 HIV-positive males (85.9% MSM; median age 44.7 years; IQR: 37.4-51.0), consecutively observed within an anal cancer screening program, after written informed consent. Indication for anal screening was given by the HIV physician during routine clinic visit. Paired oral rinse and anal samples were processed for the all HPV genotypes with QIASYMPHONY and a PCR with MY09/MY11 primers for the L1 region. RESULTS: At the oral cavity, HPV DNA was detected in 64 patients (20.9%), and in 28.1% of these cases multiple HPV infections were found. Prevalence of oral HPV was significantly lower than that observed at the anal site (p < 0.001), where HPV DNA was found in 199 cases (85.2%). Oral HPV tended to be more frequent in patients with detectable anal HPV than in those without (p = 0.08). Out of 265 HPV DNA-positive men regardless anatomic site, 59 cases (19.3%) had detectable HPV at both sites, and 51 of these showed completely different HPV types. At least one nonavalent vaccine-targeted HPV type was found in 17/64 (26.6%) of patients with oral and 199/260 (76.5%) with anal infection. At multivariable analysis, factors associated with positive oral HPV were: CD4 cells <200/µL (versus CD4 cells >200/µL, p = 0.005) and >5 sexual partners in the previous 12 months (versus 0-1 partner, p = 0.008). CONCLUSIONS: In this study on Italian HIV-positive men (predominantly MSM), oral HPV DNA was detected in approximately one fifth of tested subjects, but prevalence was significantly lower than that observed at anal site. Low CD4 cell count and increasing number of recent sexual partners significantly increased the odds of positive oral HPV. The absence of co-occurrence at the two anatomical sites may suggest different routes or timing of infection.

Incidence and Risk Factors for Hepatitis C Virus Infection among Illicit Drug Users in Italy.

So far, only three small outdated studies have investigated hepatitis C virus (HCV) incidence and risk factors among illicit drug users (DUs) in Italy. Thus, during 2007-2010, we conducted a prospective cohort study among DUs attending 17 Italian rehabilitation centers serving urban areas. Two hundred eighty-four HCV-uninfected DUs were prospectively followed by interview and anti-HCV antibody and RNA testing every 6 months. Incidence was calculated using the person-years method. Infection predictors were assessed by time-dependent Cox analysis. Participants were mostly male (83.4%), under opioid substitution therapy (OST) (78.9%), non-injecting DUs (67.9%), and with a mean age of 30.8. Ninety-one of 224 DUs initially under OST interrupted treatment during the follow-up. Overall HCV incidence was 5.83/100 person-years at risk (PYAR) [95% confidence intervals (CI), 3.63-9.38]. The incidence did not significantly differ according the participants' sociodemographic characteristics or the degree of urbanization of the towns involved in the study. The incidence was higher for DUs under than for those not under OST (6.23 vs 4.50/100 PYAR; p = 0.681). Incidence was also higher for those with than for those without OST interruption (7.17 vs 5.04/100 PYAR; p = 0.55). However, all these differences were non-significant. At last follow-up visit, a significant decrease in frequency of sharing equipment for preparation/using drugs (by injection or not) was observed by analyzing either the whole cohort or DUs under OST only. Anti-HCV seroconversion resulted independently associated with sharing drug preparation/use equipment, backloading, having a HCV-positive sexual partner, or household and (marginally) intravenous injection. In this study, HCV incidence was non-negligible and OST seemed to lack effectiveness in reducing it. In Italy, implementation of combined harm reduction interventions and antiviral treatment of chronically infected DUs would be needed.

Hepatitis E in Italy: 5 years of national epidemiological, virological and environmental surveillance, 2012 to 2016.

Increasing numbers of hepatitis E cases are being reported in several European countries, including Italy, but the burden of hepatitis E virus (HEV) infection is largely unknown in the latter. To gain a better understanding of HEV epidemiology at national level in Italy, we piloted a strengthened and integrated human (epidemiological and virological) and environmental HEV surveillance system between 2012 and 2016. Over the 5-year period, 169 confirmed hepatitis E cases were identified, with a national annual incidence of 0.72 cases per 1,000,000. Of 65 HEV-RNA positive samples of sufficient quality for molecular analysis, 66% were genotype HEV3, 32% HEV1 and 1% HEV4. The most frequent risk factor reported by all HEV3 infected cases, was the consumption of undercooked pork and sausage. For the environmental surveillance, 679 urban sewage samples were collected from 53 wastewater treatment plants and HEV-RNA was detected in 38/679 of the samples. Among these, 25 (66%) were genotype HEV3 and the remaining were HEV1. We demonstrate that autochthonous transmission and environmental circulation of genotype HEV3 is adding to travel-related HEV transmission in Italy. We recommend the 'One Health' approach to integrated surveillance, and to include HEV-related messages within health information campaigns focussing on food security.

Case report: human papilloma virus type 120-related papillomatosis mimicking laryngeal carcinoma.

INTRODUCTION: The relationship between human papilloma virus (HPV) and upper respiratory tract pathology was better understood in recent years and represents now an issue of particular interest in carcinogenesis and in immunocompromised host. We describe a case in which a rare genotype HPV-related papillomatosis mimics laryngeal carcinoma in an immunocompromised host. METHODS: A 54-year-old woman with a history of HIV-HCV coinfection and anal and laryngeal cancer successfully treated some years before was hospitalized for severe dyspnea, cough and dysphagia. Fiberoptic endoscopic evaluation raised the suspicion of tumor relapse showing the presence of a large glottic-supraglottic ulcerated mass. Several laryngeal biopsies demonstrated koilocytosis and p16 expression, according to a possible HPV infection, and focal figures of mild dysplasia of epithelium. 18 F-FDG PET/CT did not show high glycolytic activity at laryngeal level. An invasive upper respiratory tract papillomatosis in an immunocompromised host was suspected because of the patient's clinical improvement after antiretroviral therapy. CONCLUSION: Pharyngeal swab and oral rinse harboured the same HPV120 genotype sequence, a betapapillomavirus of recent description and not yet related to any similar clinical presentations.

Diagnostic performance of hepatitis E virus antigen assay in hepatitis E virus acute infection.

The aim of this study was to analyze the sensitivity of hepatitis E virus antigen (HEV-Ag) to determine acute E hepatitis. Ninety-four serum samples resulting anti-HEV IgM by DIA.PRO assay were analyzed with Wantai assay to check for HEV-Ag. Thirty samples were anti-HEV IgM positive and HEV-RNA positive, 19 samples harbored genotype 3, whereas 11 samples were genotype 1. Overall, 16% of anti-HEV IgM samples resulted HEV-Ag positive and 33.3% of HEV-RNA positive were also HEV-Ag positive. Among 64 HEV-RNA negative samples, 5 (7.8%) were HEV-Ag positive. The concordance of HEV-RNA and HEV-Ag was low (Cohen's Kappa=0.36). The Bland-Altman plot revealed a low agreement between HEV-RNA viral load and HEV-Ag, confirmed by a not significant Spearman's correlation coefficient (rho=0.137, p>0.05). Moreover, the HEV-Ag showed 100% specificity. In genotype 3f samples with a viral load >800 cp/ml HEV-Ag was positive in 80% of samples, whereas all patients harboring genotype 3e were HEV-Ag-negative irrespective of HEV-RNA viral load. Among genotype 1, HEV-Ag positivity was observed only in 27.7% patients and in all samples the viremia was >2000 cp/ml. These data suggest that anti-HEV IgM positivity represents the main biological marker of hepatitis E acute infection in clinical real life settings in developed countries.

Epidemiology of Hepatitis E Virus in European Countries.

Over the last decade the seroprevalence of immunoglobulin (IgG) anti hepatitis E virus (HEV) has been increasing in European countries and shows significant variability among different geographical areas. In this review, we describe the serological data concerning the general population and risk groups in different European countries. Anti-HEV antibody prevalence ranged from 1.3% (blood donors in Italy) to 52% (blood donors in France). Various studies performed on risk groups in Denmark, Moldova and Sweden revealed that swine farmers have a high seroprevalence of HEV IgG (range 13%-51.1%), confirming that pigs represent an important risk factor in HEV infection in humans. Subtypes 3e,f are the main genotypes detected in the European population. Sporadic cases of autochthonous genotype 4 have been described in Spain, France, and Italy. Although most HEV infections are subclinical, in immune-suppressed and transplant patients they could provoke chronic infection. Fulminant hepatitis has rarely been observed and it was related to genotype 3. Interferon and ribavirin treatment was seen to represent the most promising therapy.

HCV core antigen and HCV-RNA in HIV/HCV co-infected patients with different HCV genotypes.

BACKGROUND: A good correlation between HCV core antigen (HCVAg) and different HCV-RNA assays has been described, but little data are available in HCV/HIV co-infection. We aimed to evaluate HCVAg in comparison with HCV-RNA and to determine their kinetics during antiviral treatment in selected HCV/HIV co-infected patients. METHODS: 355 samples from 286 HCV/HIV co-infected subjects for whom HCV-RNA (Abbott RealTime) was requested were analysed also for HCVAg (Abbott ARCHITECT) in order to evaluate the correlation between the two parameters both in patients treated or untreated for chronic hepatitis C and according to different HCV genotypes. The differences between percentages were evaluated by chi square or Fisher's exact test, while mean and median values were compared by Student's t test or the Mann-Whitney test, respectively. All differences were considered significant for a p value <0.05. RESULTS: HCVAg was detectable on 288/315 sera (91.4%) positive for HCV-RNA and in 5 out of40 (12.5%) sera with undetectable HCV-RNA for a total concordance of 90.1%. The correlation was fair both in untreated (r = 0.742) and in treated (r = 0.881) patients and stronger for genotypes 1 and 4 than for genotype 3. Both HCV-RNA and HCVAg levels were significantly higher (p = 0.028 and p = 0.0098, respectively) in patients infected by genotype 1 than by genotype 3. The mean ratio of Log values between HCV-RNA (IU/mL) and HCVAg (fmol/liter) was 2.27 ± 1.09 in untreated and 2.20 ± 0.82 in treated patients (p = n.s.),consistent with a sensitivity of HCVAg corresponding to about 1,000 IU/mL of HCV-RNA, and ranged from 2.21 to 2.32 among HCV genotypes with no significant differences; five samples (1.4%; 2 genotype 1a or 1c, 3 genotype 3a) showed highly divergent values. The analysis of 18 monitoring profiles from patients treated with PEG-IFN and Ribavirin showed similar trends, except in one case in which relapse could be predicted by HCVAg and not by HCV-RNA. CONCLUSION: These results suggest that HCVAg represents an adequate tool for determining an ongoing HCV infection also in HIV co-infected patients, with lower costs and faster turnaround time than HCV-RNA.

Acute fulminant hepatitis E virus genotype 3e infection: description of the first case in Europe.

Hepatitis E virus (HEV) is the most important causative agent of acute hepatitis in developing countries. The disease is usually characterized by a self-limiting, benign course. However, when particular conditions coexist (pregnancy, old age, pre-existing liver disease) it may run an unfavourable course. To date, 4 HEV genotypes have been described. Historically, in the Western world, HEV infection was considered a travel-related disease, however in the last 2 decades a great number of non-travel-related autochthonous cases have been described, more often related to genotype 3 or 4 and in the context of zoonosis. We report the case of an elderly Italian man with an acute fulminant HEV infection genotype 3e that developed in the context of pre-existing liver disease; this is the first case of an unfavourable outcome associated with subgenotype 3e. The potential pathogenicity of this subgenotype together with the influence of host-related risk factors are discussed.