Hepatitis D virus infection in a large cohort of immigrants in southern Italy: a multicenter, prospective study.

BACKGROUND: Since few data are available in the literature on the prevalence of anti-Delta-positive subjects in immigrant populations, the aim of the present study was to evaluate the demographic and virological characteristics of HDV infection in a large cohort of immigrants living in southern Italy. METHODS: Between January 2012 and February 2020 all immigrants attending one of the 5 first- level centers were enrolled and screened for HBsAg, the HBsAg-positive for anti-Delta and if positive, for HDV-RNA and HDV genotype. RESULTS: Of the 3521 immigrants observed in the study period, 3417 (97.0%) agreed to be screened; they were mainly males (61%), with a median age of 27 years (IQR 8-74) and came prevalently (58%) from sub-Saharan Africa. Of the 3417 patients enrolled, 319 (9%) subjects were HBsAg-positive, and of those, 8 (2.5%) were anti-Delta-positive. No difference in the demographic and epidemiological characteristics was observed between the anti-Delta-negative vs -positive. Of the 8 anti-Delta-positive subjects, only one was HDV-RNA-positive (viral load: 7050 IU/mL), genotype 1, with clinical signs of cirrhosis. CONCLUSIONS: the present study showed a prevalence of HDV of 2.5% in a large cohort of asymptomatic immigrants, suggesting the need for screening campaigns for viral infections including delta hepatitis in this population.

Correction to: HBV molecular epidemiology and clinical condition of immigrants living in Italy.

The original version of this article unfortunately contained a mistake. The name of the author Mara Caroprese was rendered wrongly. The correct name is shown above.

Hepatitis C late relapse in patients with directly acting antiviral-related sustained virological response at week 12.

AIM: The aim of the present study was to identify, among the patients with failure to DAA regimen, those with a late relapse (after the achievement of a sustained virological response at week 12) and to characterize the clinical, epidemiological and virological features of these patients. MATERIAL AND METHODS: A total of 129 HCV patients with non-response to an IFN-free regimen were enrolled. Sanger sequencing of NS3, NS5A and NS5B was performed at failure by home-made protocols. RESULTS: Of the 129 patients enrolled, 8 (6.2%) experienced a breakthrough, 15 (11.7%) non-response, 99 (76.7%) a relapse by week 12 after the end of DAA therapy, and 7 (5.4%) a late relapse (after week 12; median 24 weeks, range 24-72). For two of the seven patients with a late relapse, a serum sample collected before the start of the DAA regimen was available; phylogenetic analysis showed no change in sequences of NS3, NS5A and NS5B regions, suggesting a reactivation of the initial HCV strain; for the remaining five patients, no serum collected before the DAA regimen was available, and thus, a re-infection cannot be excluded. CONCLUSIONS: Although a late relapse is infrequent, the study suggests a post-treatment follow-up of 72 weeks.

Virological patterns of HCV patients with failure to interferon-free regimens.

The study characterized the virological patterns and the resistance-associated substitutions (RASs) in patients with failure to IFN-free regimens enrolled in the real-life setting. All 87 consecutive HCV patients with failed IFN-free regimens, observed at the laboratory of the University of Campania, were enrolled. All patients had been treated with DAA regimens according to the HCV genotype, international guidelines, and local availability. Sanger sequencing of NS3, NS5A, and NS5B regions was performed at failure by home-made protocols. Of the 87 patients enrolled, 13 (14.9%) showed a misclassified HCV genotype, probably causing DAA failure, 16 had been treated with a sub-optimal DAA regimen, 19 with a simeprevir-based regimen and 39 with an optimal DAA regimen. A major RAS was identified more frequently in the simeprevir regimen group (68.4%) and in the optimal regimen group (74.4%) than in the sub-optimal regimen group (56.3%). The prevalence of RASs in NS3 was similar in the three groups (30.8-57.9%), that in NS5A higher in the optimal regimen group (71.8%) than in the sub-optimal regimen group (12.5%, P < 0.0001) and in the simeprevir regimen group (31.6%, P < 0.0005), and that in NS5B low in all groups (0-25%). RASs in two or more HCV regions were more frequently identified in the optimal regimen group (46.6%) than in the simeprevir-based regimen group (31.6%) and sub-optimal regimen group (18.7%). In our real-life population the prevalence of RASs was high, especially in NS3 and NS5A and in those treated with suitable DAA regimens.

Resistance detection and re-treatment options in hepatitis C virus-related chronic liver diseases after DAA-treatment failure.

BACKGROUND: Introduced in 2013-2014, the second- and third-wave directly acting antivirals (DAAs) have strongly enhanced the efficacy and tolerability of anti-HCV treatment, with a sustained virological response (SVR) in 90-95% of cases treated. The aim of this paper was to focus on the type and prevalence of viral strains with a reduced sensitivity to DAAs and on treatment choices for DAA-experienced patients. METHODS: The Medline was searched for "HCV infection", "HCV treatment", "Directly acting antivirals","HCV resistance". RESULTS: Most patients who did not achieve an SVR have been found to be infected with HCV mutant strains with a reduced susceptibility to these drugs. These mutants occur frequently in the NS5A region, with a moderate frequency in the NS3/4A regions and rarely in the NS5B region. Treatment-induced mutants resistant to NS5A DAAs persist for years after treatment discontinuation, whereas those resistant to the NS3 DAAs have a shorter duration. CONCLUSIONS: Patients who have failed HCV treatment with DAA agents have several re-treatment options, but re-treatment selection may be intricate and resistance testing is recommended to optimize this choice. It is, therefore, important to bear in mind that the correct determination of HCV genotype and subtype and the identification of RASs are essential elements for choosing the optimal re-treatment. It is supposed that it is useful to give readers some other suggestions regarding therapeutic reprocessing.

HBV molecular epidemiology and clinical condition of immigrants living in Italy.

INTRODUCTION: We investigated 170 HBsAg-positive immigrants living in Italy for 1-7 years to ascertain whether they may have become infected in the host country. METHODS: Of 2032 adult immigrants interviewed, 1727 (85%) voluntarily adhered to a screening program for bloodborne or sexually transmitted infections. HBsAg was detected in 170 (9.8%) screened immigrants who completed the diagnostic, clinical and therapeutic process at the nearest clinic of infectious diseases. HBV molecular biology was performed applying a homemade technology. Phylogenetic signal of the datasets was obtained by a likelihood-mapping analysis using TreePuzzle. RESULTS: Of the 170 HBsAg-positive immigrants, 133 were inactive carriers, 29 had chronic hepatitis and 8 compensated cirrhosis. HBV genotype was identified in 109 of the 113 HBV-DNA-positive immigrants and HBV-genotype-E predominated (68.9%). Of these 109, 6 (5.5%) subjects showed an HBV genotype absent or extremely rare in their native country: HBV-genotype-E in three from Eastern Europe and in one from Sri Lanka, possibly acquired from other immigrants from sub-Saharan countries, HBV-genotype-D1 in one from Burkina Faso and one from Senegal, possibly acquired in Italy. CONCLUSION: The data suggest that immigrants may acquire HBV infection in Italy and, therefore, HBV vaccination programs should be extended to all immigrants living in Italy.

Clinical Findings of HCV Chronic Infection in Undocumented Immigrants and Low-Income Refugees in Three Areas of Southern Italy.

INTRODUCTION AND AIM: In recent decades, Italy has become a land of immigration from countries suffering a socio-economic crisis. The aim of this study was to perform an organized screening to identify and offer care to immigrants with HCV infection. MATERIAL AND METHODS: The screening, performed from 2012 to 2015, involved 1,727 immigrants in the Campania and Apulia regions in southern Italy. RESULTS: Screening was accepted by 1,727 (85%) out of 2,032 immigrants interviewed; 70 (4.1%) of the 1,727 were anti-HCV-positive, all unaware of their serological condition, 31 (44.3%) of whom were HCV-RNA-positive and 39 negative. The 31 HCV-RNA-positive immigrants were further investigated at a third-level clinic of infectious diseases. The HCV viral load was 2.6 x 107 ± 7.7 x107 IU/mL, and 35.5% showed HCV-genotype 1a or 1b, 23.8% genotype 2 and 22.6% genotype 3. Two immigrants had liver cirrhosis and, in accordance with the Italian Healthcare Authority guidelines, received an interferon-free regimen and achieved a sustained virological response (SVR); 18 had chronic hepatitis, 6 of whom with a high risk of progression and received interferonbased therapy, with SVR in 4, whereas 12 at low risk were put on a waiting list for future interferon-free treatment, once licensed. The remaining 11 HCV-RNA-positive immigrants were considered HCV inactive chronic carriers and were included in a long-term observational program. CONCLUSION: The screening program can be considered successful since it was accepted by 85% of the subjects interviewed and identified 70 anti-HCV-positive immigrants, all unaware of their clinical and virological condition.

Molecular diversity in irregular or refugee immigrant patients with HBV-genotype-E infection living in the metropolitan area of Naples.

In a recent testing in the metropolitan area of Naples, Italy, on 945 irregular immigrants or refugees, 87 HBsAg chronic carriers were identified, 53 of whom were infected by HBV-genotype E. The aim of the present study was to identify the genetic diversity of HBV-genotype E in these 53 immigrants. The 53 immigrant patients with HBV-genotype-E infection were born in Africa, central or eastern Asia, eastern Europe or Latin America. These patients had been seen for a clinical consultation at one of the four first-level units from January 2012 to 2013. The first dataset contained 53 HBV-S gene isolates plus 128 genotype/subgenotype specific reference sequences downloaded from the National Center for Biotechnology Information. The second dataset, comprising the 53 HBV-S gene isolates, previously classified as HBV-genotype E, was used to perform the time-scaled phylogeny reconstruction using a Bayesian approach. Phylogenetic analysis showed that all 53 HBV-S isolates belonged to HBV-genotype E. Bayes factor analysis showed that the relaxed clock exponential growth model fitted the data significantly better than the other models. The time-scaled Bayesian phylogenetic tree of the second dataset showed that the root of the tree dated back to the year 1990 (95% HPD:1984-2000). Four statistically supported clusters were identified. Cluster A dated back to 2012 (95% HPD:1997-2012); cluster B dated back to 2008 (95% HPD:2001-2015); cluster C to 2006 (95% HPD:1999-2013); cluster D to 2004 (95% HPD:1998-2011). This study disclosed the genetic evolution and phylogenesis in a group of HBV-genotype-E-infected immigrants. J. Med. Virol. 89:1015-1024, 2017. © 2016 Wiley Periodicals, Inc.

Multiple Hepatitis B Virus (HBV) Quasispecies and Immune-Escape Mutations Are Present in HBV Surface Antigen and Reverse Transcriptase of Patients With Acute Hepatitis B.

BACKGROUND: This study characterizes and defines the clinical value of hepatitis B virus (HBV) quasispecies with reverse transcriptase and HBV surface antigen (HBsAg) heterogeneity in patients with acute HBV infection. METHODS: Sixty-two patients with acute HBV infection (44 with genotype D infection and 18 with genotype A infection) were enrolled from 2000 to 2010. Plasma samples obtained at the time of the first examination were analyzed by ultradeep pyrosequencing. The extent of HBsAg amino acid variability was measured by Shannon entropy. RESULTS: Median alanine aminotransferase and serum HBV DNA levels were 2544 U/L (interquartile range, 1938-3078 U/L) and 5.88 log10 IU/mL (interquartile range, 4.47-7.37 log10 IU/mL), respectively. Although most patients serologically resolved acute HBV infection, only 54.1% developed antibody to HBsAg (anti-HBs). A viral population with ≥1 immune-escape mutation was found in 53.2% of patients (intrapatient prevalence range, 0.16%-100%). Notably, by Shannon entropy, higher genetic variability at HBsAg amino acid positions 130, 133, and 157 significantly correlated with no production of anti-HBs in individuals infected with genotype D (P < .05). Stop codons were detected in 19.3% of patients (intrapatient prevalence range, 1.6%-47.5%) and occurred at 11 HBsAg amino acid positions, including 172 and 182, which are known to increase the oncogenic potential of HBV.Finally, ≥1 drug resistance mutation was detected in 8.1% of patients (intrapatient prevalence range, 0.11%-47.5% for primary mutations and 10.5%-99.9% for compensatory mutations). CONCLUSIONS: Acute HBV infection is characterized by complex array of viral quasispecies with reduced antigenicity/immunogenicity and enhanced oncogenic potential. These viral variants may induce difficult-to-treat HBV forms; favor HBV reactivation upon iatrogenic immunosuppression, even years after infection; and potentially affect the efficacy of the current HBV vaccination strategy.

Clinical impact of the hepatitis C virus mutations in the era of directly acting antivirals.

Introduced in 2013-2014, the second- and third-wave directly acting antivirals (DAAs) have strongly enhanced the efficacy and tolerability of anti-HCV treatment, with a sustained virological response (SVR) in 90-95% of cases treated. The majority of patients who did not achieve an SVR were found to be infected with HCV strains with a reduced susceptibility to these drugs. Indeed, the high error rate of the viral polymerase and a fast virion production (100-fold higher than the human immunodeficiency virus) result in a mixture of viral genetic populations (quasi-species) pre-existing treatment initiation. These mutants occur frequently in the NS5A region, with a moderate frequency in the NS3/4A region and rarely in the NS5B region. Treatment-induced resistant mutants to NS5A DAAs persist for years after treatment discontinuation, whereas those resistant to the NS3 DAAs have a shorter duration. This review focuses on the type and prevalence of viral strains with a reduced sensitivity to DAAs, their clinical impact and influence on the response to treatment and, consequently, on treatment choice for DAA-experienced patients. J. Med. Virol. 88:1659-1671, 2016. © 2016 Wiley Periodicals, Inc.

Effectiveness of test-and-treat model with direct-acting antiviral for hepatitis C virus infection in migrants: a prospective interventional study in Italy.

BACKGROUND: Migrants, mainly undocumented and low-income refugees, are at high risk of hepatitis C virus (HCV) infection, but are a difficult-to-reach and to-treat population. The aim of the study was to evaluate the effectiveness of a test and treat model with direct-acting antiviral for HCV infection in these migrants coming from low-income and living in southern Italy. METHODS: A prospective, multicenter, collaborative study based on a four-phase-program (educational counseling, screening, linkage-to-care and treatment) was designed in southern Italy; the study started in June 2018, was stopped in February 2020 because of the outbreak of SARS-CoV2 infection in Italy and was resumed in February 2021 until November 2021. After educational counseling on infectious diseases that are transmitted through blood or sexually pseudonymized HCV screening was offered to all undocumented migrants and low-income refugees observed at one of the 1st level clinical centers. The HCV-RNA-positive subjects were referred to one of the 3rd level units of Infectious Diseases (ID) and treated with a 12-week course of sofosbuvir-velpatasvir and observed for 12 weeks after the end of direct antiviral agents (DAA) treatment. STATISTICAL ANALYSIS: For the descriptive analysis, the categorical variables were reported as absolute numbers and relative frequencies. Continuous variables were summarized as mean and standard deviation (SD) if normally distributed, or as a median and interquartile range (IQR) if not normally distributed. We used Pearson chi-square or Fisher's exact test for categorical variables and Student's t test or Mann-Whitney test for continuous variables. A P value < 0.05 was considered to be statistically significant. Analyses were performed with SPSS 21.0. RESULTS: Of the 3501migrants observed in the study period, 3417 (97.6%) agreed to be screened; 185 (4.7%) were anti-HCV-positive and, of these, 53 (28.6%) were HCV-RNA-positive. Of these 53 subjects, 48 (90.5%) were referred to an ID unit and started DAA treatment. The HCV-RNA-positive-subjects were older [median 36 years (IQR: 32-21) vs 27.19 (IQR: 30.5-19.25); P = 0.001], and less frequently males [35 (66.03 %) vs 119 (90.1%), P < 0 .0001] than seronegative participants. They more frequently came from Eastern Europe (70.8%) stayed longer in Italy [months of stay in Italy, mean ± SD: 51.02 ± 52.84 vs 25.7 ± 42.65, P = 0.001], and had more years of schooling [years of schooling, mean ± SD: 9.61±2.81 vs 7.10 ± 4, P = 0.0001]. HCV-RNA-positive-subjects less frequently reported piercing, tattoos and tribal scars as risk factors (23.6%). Of these 48 HCV RNA positive subjects who started DAA, 47 (97.9%) showed a sustained virological response and one dropped-out in follow-up after DAA treatment. No subject had any adverse event. CONCLUSIONS: This model of HCV screening and linkage to care seems effective to eliminate HCV infectionin a difficult-to-reach and to-treat population, such as undocumented migrants and low-income refugees. The participation of cultural mediators in the study made possible a better interaction between migrants and physicians, as is evident from the large number of subjects enrolled. Eliminating HCV among migrants will have a long-term positive impact from a public health and healthcare perspective by reducing the number of individuals who potentially develop HCV-related complications such as liver cirrhosis and hepatocellular carcinoma and reducing the circulation of HCV in the regions that host them which often, as in the case of Italy, are low endemic for HCV infection.

Fatal Outcome of COVID-19 Relapse in a Fully Vaccinated Patient with Non-Hodgkin Lymphoma Receiving Maintenance Therapy with the Anti-CD20 Monoclonal Antibody Obinutuzumab: A Case Report.

Few data are available regarding the effectiveness of anti-SARS-CoV-2 vaccine in immunocompromised patients. Vaccination may have a suboptimal efficacy in this population, in particular if patients are exposed to anti-B-cell therapy. We report the virological and clinical characteristics of a patient with follicle center lymphoma under bimonthly maintenance therapy with obinutuzumab, an anti-CD20 monoclonal antibody. Despite three doses of BNT162b2 vaccine, the patient was infected by the SARS-CoV-2 Omicron variant. After an initial period of clinical and molecular remission due to early therapy with sotrovimab, the patient experienced a fatal relapse sustained by the same viral strain.

Virological Factors Associated with Failure to the Latest Generation of Direct Acting Agents (DAA) and Re-Treatment Strategy: A Narrative Review.

The availability of all oral direct acting antiviral agents (DAAs) has revolutionized the management of HCV infections in recent years, allowing to achieve a sustained virological response (SVR) in more than 95% of cases, irrespective of hepatitis C Virus (HCV) genotype or staging of liver disease. Although rare, the failure to the latest-generation regimens (grazoprevir/elbasvir, sofosbuvir/velpatasvir, pibrentasvir/glecaprevir) represents a serious clinical problem, since the data available in the literature on the virological characteristics and management of these patients are few. The aim of the present narrative review was to provide an overview of the impact of baseline RASs in patients treated with the latest-generation DAAs and to analyze the efficacy of the available retreatment strategies in those who have failed these regimens.

Genetic Variability in Patients with HCV-Related Hepatocellular Carcinoma.

BACKGROUND: The present paper evaluates the genetic variability of HCV in patients with hepatocellular carcinoma (HCC). METHODS: Amino acid substitutions (aas) in NS3, NS5A and core regions were analyzed in 17 patients with HCC (Cases) and 13 without HCC (Controls), all naïve to DAAs. For the Cases, a sample of neoplastic liver tissue, non-neoplastic liver tissue and a serum sample were collected; for the Controls, a sample of liver tissue was collected. Sanger sequencing of three regions was performed using homemade protocols. RESULTS: Phylogenetic trees showed that there was no difference in the virus populations in the three compartments analyzed for the three HCV regions in patients with HCC. Low variability and no difference between the Cases and Controls were observed in the core and NS5A regions; however, in the NS3 region, a higher variability was observed in the Cases. No difference was observed in the core region between Cases and Controls. In NS3, aa substitutions at positions 103 and 122 were more frequently found in Cases than Controls (in both cases 50% vs 9.1%, p<0.05); moreover, aas in positions 32, 44 (p=0.035 for both), 79 (p=0.008) and 121 (p=0.018) were observed in the Cases and absent in the Controls. Finally, considering the NS5A region, aa substitutions at positions 37 and 54 were more frequently identified in the Cases than the Controls, but without statistical significance. CONCLUSION: These data may suggest a higher aa variability in patients with HCC than in those without, especially in the NS3 region.

HBeAg Levels Vary across the Different Stages of HBV Infection According to the Extent of Immunological Pressure and Are Associated with Therapeutic Outcome in the Setting of Immunosuppression-Driven HBV Reactivation.

HBeAg is a marker of HBV-activity, and HBeAg-loss predicts a favorable clinical outcome. Here, we characterize HBeAg-levels across different phases of HBV infection, their correlation with virological/biochemical markers and the virological response to anti-HBV therapy. Quantitative HBeAg (qHBeAg, DiaSorin) is assessed in 101 HBeAg+ patients: 20 with acute-infection, 20 with chronic infection, 32 with chronic hepatitis and 29 with immunosuppression-driven HBV-reactivation (HBV-R). A total of 15/29 patients with HBV-R are monitored for >12 months after starting TDF/ETV. qHBeAg is higher in immunosuppression-driven HBV-R (median[IQR]:930[206-1945]PEIU/mL) and declines in chronic hepatitis (481[28-1393]PEIU/mL, p = 0.03), suggesting HBeAg production, modulated by the extent of immunological pressure. This is reinforced by the negative correlation between qHBeAg and ALT in acute infection (Rho = -0.66, p = 0.006) and chronic hepatitis (Rho = -0.35; p = 0.05). Interestingly, qHBeAg strongly and positively correlates with qHBsAg across the study groups, suggesting cccDNA as a major source of both proteins in the setting of HBeAg positivity (with limited contribution of integrated HBV-DNA to HBsAg production). Focusing on 15 patients with HBV-R starting TDF/ETV, virological suppression and HBeAg-loss are achieved in 60% and 53.3%. Notably, the combination of qHBeAg > 2000 PEIU/mL + qHBsAg > 52,000 IU/mL at HBV-R is the only factor predicting no HBeAg loss (HBeAg loss: 0% with vs. 72.7% without qHBeAg > 2000 PEIU/mL + qHBsAg > 52,000 IU/mL, p = 0.03). In conclusion, qHBeAg varies over the natural course of HBV infection, according to the extent of immunological pressure. In the setting of HBV-R, qHBeAg could be useful in predicting the treatment response under immunosuppression.

Current Status of Laboratory Diagnosis for COVID-19: A Narrative Review.

The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the related disease (COVID-19) has spread rapidly to pandemic proportions, increasing the demands on healthcare systems for the containment and management of COVID-19. One of the critical issues to be addressed is the improvement in laboratory diagnosis and screening of large portions of the population to stop the virus spreading. Currently, the laboratory diagnosis of SARS-CoV-2 infection and the related disease is based on the research of viral RNA with rt-PCR methods in upper and lower respiratory airways. Serological tests to detect SARS-CoV-2 antibodies could help physicians and healthcare workers to support COVID-19 diagnosis and follow-up and perform population screening. Our review, using MEDLINE and EMBASE, summarizes the current knowledge of direct and serological tests performed to research RNA, antigens, or antibodies for SARS-CoV-2, evaluating the advantages and drawbacks for specific tests.

Assessment and Comparison of Two Serological Approaches for the Surveillance of Health Workers Exposed to SARS-CoV-2.

BACKGROUND AND AIM: The aim of the present study was to assess the diagnostic performance of an LFA compared with an ELISA test in a cohort of HWs operating in a COVID-19 unit of a teaching hospital in southern Italy. METHODS: We performed an observational, prospective, interventional study including 65 COVID-19 unit personnel. On a total of 196 serum samples (at least 2 serum samples for each HW), LFA and ELISA tests for SARS-COV-2 IgG and IgM were performed. Also, 32 serum samples of SARS-CoV-2 RNA positive patients at least 21 days before sampling, and 30 serum samples of patients obtained up to November 2019, before COVID-19 outbreak in China, were used as positive and negative controls, respectively. FINDINGS: Of the 65 HWs enrolled, 6 were positive in LFA; overall, of the 196 serum samples, 20 were positive in LFA. All ELISA tests performed on serum samples collected from HWs were negative. The specificity of LFAs was 90.77% considering the 65 HWs and 89.80% considering all the 196 health workers serum samples analyzed. Considering the data on HWs, ELISA test for SARS-COV-2 antibodies showed a specificity of 100%, including all the 196 serum samples collected, and 100% including the 65 HWs. The ELISA and LFAs performed after 21 days last COVID-19 patient was discharged were all negative. CONCLUSION: LFAs compared to ELISA tests result in less specificity, considering COVID-19 negative personnel and patients. Thus, LFAs seem to be not adequate in the active surveillance of HWs.

Blood-borne chronic viral infections in a large cohort of immigrants in southern Italy: A seven-centre, prospective, screening study.

BACKGROUND: Aim of this study was to evaluate the prevalence of blood-borne chronic viral infections in immigrants living in southern Italy and identify factors associated to viral infections. METHODS: A prospective screening program was performed in seven clinical centers operating in Campania, Apulia and Calabria regions in southern Italy, in order to identify immigrants with HBV, HCV or HIV infections. RESULTS: Of 4,125 immigrants observed in the study period, 3,839 (93.0%) agreed to be screened: 381 (9.9%) resulted HBsAg-positive, 136 (3.5%) anti-HCV, 62 (1.6%) anti-HIV and 1,448 (37.7%) HBsAg-negative and anti-HBc-positive. Ongoing or previous HBV infection was observed more frequently in males (p = 0.02 and p < 0.001, respectively), whereas HIV infection in females (p = 0.01). Immigrants from western Africa showed a higher rate of HBsAg positivity (p < 0.0001), HBsAg negativity/anti-HBc positivity (p < 0.0001) and anti-HIV positivity (p = 0.004) compared with those from other geographical areas. At multivariate analysis, ongoing HBV infection was associated with male sex (OR 1.49, 95% CI: 1.04-2.14) and origin from western Africa (OR 4.67, 95% CI: 1.70-12.80) and eastern Europe (OR 3.44, 95% CI: 1.17-10.08). HCV infection showed the tendency to be more frequent among males (OR 1.84, 95% CI: 0.99-3.42). HIV infection was associated with an older age (OR 1.04, 95% CI: 1.01-1.06), origin from western Africa (OR 4.09, 95% CI: 1.26-13.29) and female sex (OR 2.38, 95% CI: 1.29-4,39; p = 0.006). CONCLUSIONS: The high prevalence of HBV, HCV and HIV infections in our large cohort of immigrants should definitively prompt Italian Healthcare Authorities to develop adequate cost-effective screening policies.

Patients with HCV genotype-1 who have failed a direct-acting antiviral regimen: virological characteristics and efficacy of retreatment.

BACKGROUND: This real-world clinical setting study characterized the virological patterns in genotype-1 patients failing interferon (IFN)-free regimens and evaluated the efficacy of re-treatment. METHODS: A total of 73 consecutive patients failing IFN-free regimens were enrolled (17 genotype-1a and 56 -1b). At failure Sanger sequencing of NS3, NS5A and NS5B regions was performed by home-made protocols. RESULTS: In patients having failed an NS3 inhibitor, the prevalence of NS3-RASs was higher in the 10 with genotype-1a than in the 24 with genotype-1b (80% versus 41.6%). In patients treated with an NS5A inhibitor, the prevalence of NS5A-RASs was very high in the 14 with genotype-1a and the 27 with genotype-1b (78.6% and 92.5%, respectively). In patients having failed sofosbuvir, the prevalence of NS5B-RASs was more frequently identified in the 45 with genotype-1b than in the 10 with genotype-1a (37.7% versus 10%). The prevalence of NS5B-RASs in patients having failed dasabuvir was high in both genotypes, 66.6% in the 6 with genotype-1a and 45.5% in the 11 with genotype-1b. The 6 patients re-treated with genotype-1a less frequently (50%) showed sustained virological response (SVR) than the 18 with genotype-1b (88.8%; P=0.07). SVR was more frequent in the 21 patients with an effective second-line direct-acting antiviral (DAA) regimen than the 3 without (90.4% versus 0%; P<0.005). CONCLUSIONS: The prevalence of RASs was high in our real-world population. NS3, NS5A and NS5B sequencing seems mandatory in the choice of DAA re-treatment.