Characterization of hepatitis virus co-infections in a cohort of immigrants living in southern Italy.

To characterize viral hepatitis co-infections in a cohort of immigrants living in southern Italy. In a prospective multicenter study, all undocumented immigrants and low-income refugees consecutively evaluated for a clinical consultation at one of the five first-level clinical centers in southern Italy from January 2012 to February 2020 were enrolled. All subjects included in the study were screened for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) and anti-HIV; the HBsAg-positive were screened also for anti-delta. Of the 2923 subjects enrolled, 257 (8%) were HBsAg-positive alone (Control group B), 85 (2.9%) only anti-HCV-positive (Control group C), 16 (0.5%) HBsAg/anti-HCV-positive (Case group BC), and 8 (0.2%) HBsAg/anti-HDV-positive (Case group BD). Moreover, 57 (1.9%) subjects were anti-HIV-positive. HBV-DNA positivity was found less frequently in the 16 subjects in Case group BC (43%) and in the 8 in Case group BD (12.5%) than in the 257 in Control group B (76%; p = 0.03 and 0.0000, respectively). Similarly, HCV-RNA positivity was more frequent in Case group BC than in Control group C (75% vs. 44.7% p = 0.02). The subjects in Group BC had a lower prevalence of asymptomatic liver disease (12.5%) than Control group B (62.2%, p = 0.0001) and Control group C (62.3%, p = 0.0002). Conversely, liver cirrhosis was more frequently identified in Case group BC (25%) than in Control groups B and C (3.11% and 2.35%, p = 0.0000 and 0.0004, respectively). The present study contributes to the characterization of hepatitis virus co-infections in the immigrant population.

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.

HDV infection in immigrant populations.

AIMS: Little data have been published so far on the epidemiological aspects of hepatitis D virus (HDV) infection in immigrant populations and even poorer is the information on the virological, phylogenetic, and clinical aspects of this infection in these populations. This review article, aimed primarily at physicians caring for immigrants, summarizes the information available on HDV infection and analyzes data on this topic concerning the immigrant populations. METHODS AND RESULTS: The prevalence of HDV infection in HBsAg-positive immigrants varies according to the country of origin. For example, in immigrants from sub-Saharan Africa, this prevalence is higher in those born in Equatorial Guinea (24.4%) than those from other African countries (10.3%). The epidemiological impact of HDV infection linked to migratory flows is a function of the different endemicity between countries of origin and countries in which a new existence has been established. This impact is high when immigrants from areas endemic to HDV infection (eg, Equatorial Guinea) settle in areas of low endemicity (eg, Germany or England, with a prevalence of around 4%), while the impact is lesser or nonexistent if the migratory flows are directed toward countries with intermediate endemicity (eg, Italy and Greece, with a prevalence of around 10%). CONCLUSION: This impact of immigration on HDV epidemiology can be strong when HDV endemicity is high in the country of origin and low in the host country and slight when immigrants move to high or medium endemic countries.

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.

Hepatitis B virus, hepatitis C virus and human immunodeficiency virus infection in undocumented migrants and refugees in southern Italy, January 2012 to June 2013.

Screening of undocumented migrants or refugees for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections has been offered free of charge and free from bureaucratic procedures since 2012 at four primary-level clinical centres in Naples and Caserta, Italy. Of 926 undocumented migrants and refugees visiting one of the primary-level clinical centres from January 2012 to June 2013, 882 (95%) were screened for hepatitis B surface antigen (HBsAg), total hepatitis B core antibody (anti-HBc) and antibodies against HCV and HIV. Of the 882 individuals enrolled, 78 (9%) were HBsAg positive, 35 (4%) anti-HCV positive and 11 (1%) anti-HIV positive (single infections); seven (1%) had more than one infection (three were HBsAg positive). Of the 801 HBsAg-negative patients, 373 (47%) were anti-HBc positive. The HBsAg-positivity rate was high (14%; 62/444) in individuals from sub-Saharan Africa and intermediate in those from eastern Europe (6%; 12/198), northern Africa (2%; 2/80) and Bangladesh, India, Pakistan and Sri Lanka (the 'India-Pakistan area') (3%; 4/126). Anti-HCV was detected in 9/126 (7%) individuals originating from the India-Pakistan area, in 12/198 (6%) from eastern Europe, in 17/444 (4%) from sub-Saharan and in 2/80 (2%) from northern Africa. The HBV, HCV and HIV infections in the undocumented migrants and refugees screened serve as a reminder to the Italian healthcare authorities to carry out extensive screening and educational programmes for these populations.

Molecular epidemiology of hepatitis B virus genotypes circulating in acute hepatitis B patients in the Campania region.

Fifty-three HBV-DNA-positive patients with symptomatic acute hepatitis B were enrolled from 1999 to 2010 to evaluate molecular and phylogenetic changes in HBV in southern Italy. HBV polymerase region was evaluated by direct sequencing in plasma samples obtained at first observation. Different data sets were aligned and a phylogenetic tree was inferred using PhyML program. Statistical robustness was confirmed with a bootstrap analysis. A Bayesian Markov chain Monte Carlo method and a Bayesian skyline plot were used to estimate the evolution of our samples. The dN/dS rate (ω) was estimated by the maximum likelihood approach to investigate the presence of codons under positive selection. The MacClade program was used to test viral gene out/in flow only among HBV-D3 subgenotype patients with different risk factors. Of the 53 patients, 83% were born in Italy and 17% were foreigners. HBV genotype D was prevalent (64.1%), followed by genotype A (26.4%), E (3.8%), and F (5.7%). The prevalent subgenotype was D3 (70.6%). The Bayesian tree of the 24 D3 subgenotypes showed two main clades both dated 1994; 40% of viral gene flow observed was from intravenous drugs users and heterosexual patients. Phylogenetic analysis of HBV isolates showed that HBV-D3 remains the prevalent genotype, but also subgenotype A2 has become frequent in southern Italy. This may be of clinical relevance in years to come, since patients with HBV-genotype-A chronic infection less frequently than those with genotype D develop HBeAg-negative chronic hepatitis and respond more frequently to alfa-interferon treatment.

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.

Clinical presentation, outcome, and response to therapy among patients with acute exacerbation of chronic hepatitis C.

BACKGROUND & AIMS: The slow asymptomatic progression of chronic hepatitis C (CHC) can be interrupted by an acute exacerbation, characterized by increased serum levels of alanine aminotransferase (ALT) and bilirubin and other symptoms of acute hepatitis. We aimed to provide more information about the clinical presentation of acute exacerbation of CHC. METHODS: We identified 82 consecutive patients, from 2 locations in Italy, who had an acute exacerbation of CHC from January 2005 through June 2010; we followed them up for a median period of 36 months. These cases were hepatitis C virus (HCV) RNA positive, hepatitis B surface antigen-negative, and had not received anti-HCV therapy. They were matched with 82 subjects with hepatitis C without reactivation for age, sex, and HCV genotype (controls). Sixty-nine cases and 73 controls were followed up for at least 2 years. Liver biopsy specimens had been taken from 23 cases and 31 controls-once before enrollment in the study and once during the follow-up period. RESULTS: HCV genotype 2 was detected in 46.4% of cases, and HCV genotype 1 was detected in 43.9%. Among cases, the mean ALT level was 1063 ± 1038 IU/dL, and the mean total bilirubin level was 15.87 ± 7.15 mg/dL. A higher percentage of cases carried the interleukin-28B CC genotype than controls (40.2% vs 24.4%; P < .05). Among cases, 43.5% had a steady increase in ALT level (>2-fold baseline value); for 56.5% of these patients, ALT levels returned to baseline values before the acute exacerbation of chronic hepatitis. Based on comparisons of biopsy specimens, 18 cases (78.3%) and 11 controls (35.5%) had increasing fibrosis, with Ishak scores increasing by more than 2 (P < .005); 14 cases (60.9%) and 3 controls (9.6%) had increases in necroinflammation of more than 2 points (P < .005). Thirty-two cases (46.4%) and 38 controls (52%) received treatment with pegylated interferon and ribavirin; a sustained virologic response was achieved in 26 cases (81.2%) and 23 controls (60.5%). CONCLUSIONS: Although an acute exacerbation of chronic hepatitis is a serious medical condition, most patients achieve a sustained virologic response after treatment with pegylated interferon and ribavirin.

An Unusual Case of a Double Tricuspid and Mitral Valves Infective Endocarditis Complicated by Multiple Septic Embolisms Secondary to an Atrial Septal Defect: A Case Report and Review of Literature.

Multivalvular endocarditis (MVE) is an uncommon infection that mostly involves mitral and aortic valves, and it is related to a higher risk of congestive heart failure and a higher mortality. We described a case of a bilateral MVE and performed a review of the literature on similar clinical cases. We reported an unusual case of a 68-year-old male patient with a tricuspid and mitral infective endocarditis due to a methicillin-resistant Staphylococcus aureus complicated by multiple right- and left-sided septic embolization (lungs, brain, spleen, L2-L3 vertebral bones) due to an unknown atrial septal defect identified and repaired during cardiac surgery. Despite the severity of the clinical case, the patient experienced a good clinical outcome also thanks to a multidisciplinary approach. We identified 21 case reports describing bilateral MVE. A multidisciplinary approach is essential in the management of valve diseases to improve the prognosis of patients, especially in bilateral MVE.

Different Clinical Outcomes of COVID-19 in Two Healthcare Workers Vaccinated with BNT162b2 Vaccine, Infected with the Same Viral Variant but with Different Predisposing Conditions for the Progression of the Disease.

Safe and effective vaccines are available to face the global threat of the COVID-19 pandemic. In this article, we report on the clinical cases of two healthcare workers vaccinated with two doses of BNT162b2 vaccine who were infected by the same viral clade but had different clinical outcomes.

Hepatitis C virus (HCV) micro-elimination in the hospital setting: The results of the HCV Caserta hospital project.

BACKGROUND: In the present study we evaluated the efficacy of an innovative model of HCV micro-elimination in a hospital setting in an area of high HCV prevalence. PATIENTS AND METODS: Between January and December 2019, a prospective, interventional study for a program of HCV case-finding and linkage-to-care was performed in S. Anna and S. Sebastiano hospital of Caserta, in Campania, a region in southern Italy. All adult patients who were admitted to the Caserta hospital in the study period and resulted positive for anti-HCV were included in the study. The outcomes evaluated were the number of subjects resulting HCV-RNA-positive, those linked-to-care and treated with a DAA and the subjects whose anti-HCV-status was unknown. RESULTS: In the study period, 14,396 subjects, admitted to the hospital for different reasons, were tested for anti-HCV: 529 (3.7%) subjects resulted positive for anti-HCV. Of the 529 anti-HCV-positive subjects, 10 died during hospitalization and 243 were already treated with a DAA. The remaining 276 subjects were contacted and agreed to be evaluated. Of these 276 subjects, 68 patients resulted HCV- RNA-negative and 194 HCV-RNA-positive and 180 of these were treated with a DAA according to the international guidelines. DISCUSSION: A simple, rapid, inexpensive model of HCV micro-elimination in the hospital setting allowed us to find anti-HCV-positive subjects with unknown anti-HCV status or not linked to a clinical center.

COVID-19 as Another Trigger for HBV Reactivation: Clinical Case and Review of Literature.

Universal hepatitis B virus (HBV) vaccination has been applied for years in most countries, but HBV infection remains an unresolved public health problem worldwide, with over one-third of the world's population infected during their lifetime and approximately 248 million hepatitis B surface antigen (HBsAg) chronic carriers. HBV infection may reactivate with symptomatic and sometimes life-threatening clinical manifestations due to a reduction in the immune response of various origins, due to chemotherapy or immunosuppressive therapy, treatments increasingly practiced worldwide. SARS-CoV-2 and its COVID-19 associated disease have introduced new chances for HBV reactivation due to the use of dexamethasone and tocilizumab to counteract the cytokine storm. This could and should be prevented by accurate screening of HBV serologic markers and adequate pharmacologic prophylaxis. This article describes the case of a patient with COVID-19 who developed HBV reactivation and died of liver failure and analyzes published data on this setting to provide useful information to physicians who manage these patients during the SARS-CoV-2 pandemic.

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.

Dynamics of Lipid Profile in Antiretroviral-Naïve HIV-Infected Patients, Treated with TAF-Based Regimens: A Multicenter Observational Study.

Background: The introduction of tenofovir alafenamide (TAF) in antiretroviral therapy has deeply modified the choice of the backbone for different treatment regimens, allowing the prevention of the bone and renal toxicity that was related to the previous formulation of tenofovir disoproxil fumarate (TDF). At the same time, literature data show an onset of dyslipidemia after a switch from TDF to TAF. To better understand the possible role of TAF in dyslipidemia, antiretroviral-naïve HIV-infected patients were evaluated, comparing those treated with TAF/emtricitabine with those with abacavir/lamivudine. Methods: We enrolled 270 antiretroviral-naïve HIV-infected patients in an observational, retrospective, longitudinal, multicenter study; they started treatment from 2017 to 2019 and were followed up for at least 72 weeks. We divided patients into two groups, one treated with a TAF-based backbone in their antiretroviral regimens (TAF group) and one without TAF (NO TAF group), to evaluate possible differences in the dynamics of lipid profiles from baseline(T0) to week 24 (T24), 48 (T48) and 72 (T72). Results: No significant differences were observed at baseline between the 2 groups. In the TAF group we observed a significant development of hypercholesterolemia throughout the follow-up (p < 0.0001), not evident in the NO TAF group, that instead showed a significant increase in high-density lipoprotein (HDL). There were no significant differences between the two groups regarding triglycerides, low-density lipoprotein (LDL) and cardiovascular risk index (CRI). A cholesterol-lowering treatment with statin, finally, was prescribed in 6 patients in both groups during the study. At binary logistic regression analysis, no factor was independently associated with hypercholesterolemia, except for higher age at T0. Conclusions: This real-life study shows that in HIV-naïve patients, TAF was associated with hypercholesterolemia throughout the follow-up. The clinical significance of this hypercholesterolemia will have to be clarified in further studies.