Risk of parenterally transmitted hepatitis following exposure to invasive procedures in Italy: SEIEVA surveillance 2000-2021.

BACKGROUND & AIMS: Surgical interventions and invasive diagnostic/therapeutic procedures are known routes of transmission of viral hepatitis. Using data from the Italian surveillance system for acute viral hepatitis (SEIEVA), the aim of this study was to investigate the association between specific types of invasive procedures and the risk of acute HBV and HCV infections. METHODS: Data from SEIEVA (period 2000-2021) were used. The association between acute HBV and HCV infection and potential risk factors, i.e. surgical interventions and diagnostic/therapeutic procedures (given according to the ICD-9-CM classification), was investigated in comparison to age-matched hepatitis A cases, used as controls, by conditional multiple logistic regression analysis. RESULTS: A total of 8,176 cases with acute HBV, 2,179 with acute HCV, and the respective age-matched controls with acute HAV infection were selected for the main analysis. Most of the procedures evaluated were associated with the risk of acquiring HBV or HCV. The strongest associations for HBV infection were: gynaecological surgery (odds ratio [OR] 5.19; 95% CI 1.12-24.05), otorhinolaryngological surgery (OR 3.78; 95% CI 1.76-8.09), and cardiac/thoracic surgery (OR 3.52; 95% CI 1.34-9.23); while for HCV infection, they were: neurosurgery (OR 11.88; 95% CI 2.40-58.85), otorhinolaryngological surgery (OR 11.54; 95% CI 2.55-52.24), and vascular surgery (OR 9.52; 95% CI 3.25-27.87). Hepatitis C was also strongly associated with ophthalmological surgery (OR 8.32; 95% CI 2.24-30.92). Biopsy and/or endoscopic procedures were significantly associated with both HCV (OR 3.84; 95% CI 2.47-5.95) and, to a lesser extent, HBV infection (OR 1.48; 95% CI 1.16-1.90). CONCLUSIONS: Despite the progress made in recent years, invasive procedures still represent a significant risk factor for acquiring parenterally transmitted hepatitis viruses, thus explaining the still numerous and unexpected cases diagnosed among the elderly population in Italy. Our results underline the importance of observing universal precautions to control the iatrogenic transmission of hepatitis viruses. IMPACT AND IMPLICATIONS: Cases of parenterally transmitted acute viral hepatitis in the elderly population, that are difficult to explain based on the most widely recognised risk factors, continue to be diagnosed in Italy. Based on the Italian SEIEVA surveillance of acute viral hepatitis data, this study highlights an increased risk of acquiring hepatitis B and C following exposure to invasive procedures, which might explain the observed cases in elderly individuals. Furthermore, this finding emphasises the need to observe universal precautions strictly, in healthcare settings, including in the case of minor surgical procedures.

Acute Delta Hepatitis in Italy spanning three decades (1991-2019): Evidence for the effectiveness of the hepatitis B vaccination campaign.

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come.

Risk of SARS-CoV-2 infection in migrants and ethnic minorities compared with the general population in the European WHO region during the first year of the pandemic: a systematic review.

BACKGROUND: Migrants and ethnic minorities have suffered a disproportionate impact of the COVID-19 pandemic compared to the general population from different perspectives. Our aim was to assess specifically their risk of infection in the 53 countries belonging to the World Health Organization European Region, during the first year of the pandemic. METHODS: We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO CRD42021247326). We searched multiple databases for peer-reviewed literature, published on Medline, Embase, Scisearch, Biosis and Esbiobase in 2020 and preprints from PubMed up to 29/03/2021. We included cross-sectional, case-control, cohort, intervention, case-series, prevalence or ecological studies, reporting the risk of SARS-CoV-2 infection among migrants, refugees, and ethnic minorities. RESULTS: Among the 1905 records screened, 25 met our inclusion criteria and were included in the final analysis. We found that migrants and ethnic minorities during the first wave of the pandemic were at increased exposure and risk of infection and were disproportionately represented among COVID-19 cases. However, the impact of COVID-19 on minorities does not seem homogeneous, since some ethnic groups seem to be more at risk than others. Risk factors include high-risk occupations, overcrowded accommodations, geographic distribution, social deprivation, barriers to access to information concerning preventive measures (due to the language barrier or to their marginality), together with biological and genetic susceptibilities. CONCLUSIONS: Although mixed methods studies will be required to fully understand the complex interplay between the various biological, social, and cultural factors underlying these findings, the impact of structural determinants of health is evident. Our findings corroborate the need to collect migration and ethnicity-disaggregated data and contribute to advocacy for inclusive policies and programmatic actions tailored to reach migrants and ethnic minorities.

Hepatitis of unknown aetiology in children - epidemiological overview of cases reported in Europe, 1 January to 16 June 2022.

Following the report of an excess in paediatric cases of severe acute hepatitis of unknown aetiology by the United Kingdom (UK) on 5 April 2022, 427 cases were reported from 20 countries in the World Health Organization European Region to the European Surveillance System TESSy from 1 January 2022 to 16 June 2022. Here, we analysed demographic, epidemiological, clinical and microbiological data available in TESSy. Of the reported cases, 77.3% were 5 years or younger and 53.5% had a positive test for adenovirus, 10.4% had a positive RT-PCR for SARS-CoV-2 and 10.3% were coinfected with both pathogens. Cases with adenovirus infections were significantly more likely to be admitted to intensive care or high-dependency units (OR = 2.11; 95% CI: 1.18-3.74) and transplanted (OR = 3.36; 95% CI: 1.19-9.55) than cases with a negative test result for adenovirus, but this was no longer observed when looking at this association separately between the UK and other countries. Aetiological studies are needed to ascertain if adenovirus plays a role in this possible emergence of hepatitis cases in children and, if confirmed, the mechanisms that could be involved.

[An update on the epidemiology of hepatitis A in Italy 2015-2019. Data from the surveillance of acute viral hepatitis SEIEVA]. / Aggiornamento sull'epidemiologia dell'epatite A in Italia negli ultimi cinque anni. Dati dalla sorveglianza SEIEVA 2015-2019.

BACKGROUND: hepatitis A is an infective disease whose global diffusion appears to be variable and strictly related to socioeconomic status, hygiene conditions, and access to potable water. During last twenty years, Italy registered a constant decrease of new cases with recurrent epidemic outbreaks. OBJECTIVES: to outline the hepatitis A epidemiological situation in Italy in the five-year period 2015-2019. DESIGN: descriptive study based on cases reported to the National Surveillance System for Acute Viral Hepatitis (SEIEVA). SETTING AND PARTICIPANTS: hepatitis A cases reported to SEIEVA from 2015 to 2019. MAIN OUTCOME MEASURES: hepatitis A incidence, percentages of cases exposed to known risk factors, distribution of cases by vaccination status. RESULTS: during the whole observational period, SEIEVA registered 4,929 type A hepatitis cases. The epidemic curve initially showed a trend with a low incidence level interrupted in August 2016 with the onset of a large epidemic, in the period between August 2016 and December 2017, involving 3,428 cases mostly adult men exposed to homosexual intercourses (MSM). Since January 2018, the trend of the cases has been decreasing even though its level is still higher than the pre-epidemic period. Based on the analysis of the epidemic curve, three periods characterized by different trends in the monthly number of notified cases were identified: January 2015-July 2016 (pre-epidemic period), August 2016-December 2017 (epidemic period), January 2018-December 2019 (post-epidemic period). In the last observation period, cases show different characteristics compared to the previous periods. They are mainly males under 18 years (p=0.026), subjects travelling to Morocco (8.9% vs 15.9%; p< 0.001) or being in contact with an infected person (p< 0.001). The multivariate analysis confirmed a significantly higher probability for cases notified in the post-epidemic period, compared to the pre-epidemic, to be secondary cases or to have traveled to Morocco. Compared to the pre-epidemic period and the epidemic period, there was a higher percentage of subjects who received a single dose of anti-hepatitis A vaccine (p=0.001). Taking into account only secondary cases reported in the third period, the percentage of cases with incomplete vaccination rises to 31%; in this group, a single dose of the vaccine was administered at a median of 11.5 days before the onset of symptoms. CONCLUSIONS: vaccination is of paramount importance for the prevention of hepatitis A in all risk groups, including adult males exposed to same-sex sexual intercourse and travelers to areas at high-medium endemic level, especially children, as the timeliness in the vaccination of contacts is fundamental and crucial for interrupting the chains of infection. The observed increase in secondary cases and the delay in the administration of doses lead to a reflection on the need for greater promotion of vaccination, but also highlight the critical issues in the organization of vaccination services, mainly in the areas that have reported the greatest number of cases.

[Epidemiology and surveillance of hepatitis E in Italy: data from the SEIEVA surveillance system 2007-2019]. / Epidemiologia e sorveglianza dell'epatite E in Italia: dati dalla sorveglianza SEIEVA 2007-2019.

BACKGROUND: hepatitis E is a disease spread all over the world, with endemic levels varying according to ecological and socioeconomic factors. In developing countries, large epidemics spread mainly through contaminated water; in developed countries, hepatitis E has always been considered a sporadic disease, closely associated to the travels to endemic areas, especially in Southeastern Asia. In the last years, this perception is significantly changing, because of an increasing number of autochthonous cases reported in many European countries. OBJECTIVES: to describe the epidemiological picture of hepatitis E in Italy from 2007 to 2019. DESIGN: descriptive study based on the cases reported to the special surveillance of acute viral hepatitis (SEIEVA); case-control analytical study for the analysis of risk factors associated with hepatitis E. SETTING AND PARTICIPANTS: hepatitis E cases reported to SEIEVA in the period 2007-2019. MAIN OUTCOME MEASURES: number of cases notified by year, percentages of cases exposed to known risk factors, odds ratios. RESULTS: from January 2007 to June 2019, 385 hepatitis E cases were notified to SEIEVA. The annual number increased from 12 in 2007 to 49 in 2018, the increasing trend continued in 2019, when 39 cases were observed in the first 6 months of the year. Northern and Central Regions reported most of the cases; only a few were diagnosed in Southern Regions. Based on SEIEVA data, the trend of hepatitis E notifications has increased according to the increasing propensity to the differentiated diagnosis, at least until 2018. However, only 46% of suspected cases are tested to detect the presence of anti-HEV IgM antibodies, during the observation period; the percentage of tested cases is significantly lower in the South than in Northern and Central Italy (p<0.001). The reported cases have a median age of 48 years (range: 5-87) and are mostly males (80%); 32% was observed in foreign citizens mainly from endemic areas of South Asia (Bangladesh, India, and Pakistan). In 72.5% of cases, the infection was contracted in Italy. The most frequent risk factor is the consumption of raw or undercooked pork meat, especially sausages (70% of cases), significantly associated with hepatitis E risk (OR 3.0; IC95% 1.4-6.1). Other important risk factors are wild boar sausages consumption (40% of cases, OR 4.6, not statistically significant), and travels to endemic areas during the six weeks before the disease (31% of cases, OR 3.2; IC95% 1.6-6.4). CONCLUSIONS: hepatitis E can now be considered as endemic even in industrialized countries. In Italy, from 2007 an increasing number of cases has been reported. However, the real impact of HEV infection is still underestimated due to the limited number of clinical centres which perform tests for the search of anti-HEV IgM antibodies in cases of acute hepatitis. An ad hoc surveillance has been activated in January 2019 in some Local Health Units/Regions and extended to a national level starting from January 2020. This initiative is necessary in order to better dimension the burden of the disease associated with HEV infection, to study its epidemiology, and to increase awareness of this infection among health professionals.

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.

Acute Hepatitis B After the Implementation of Universal Vaccination in Italy: Results From 22 Years of Surveillance (1993-2014).

BACKGROUND: Hepatitis B vaccination has proven to be very safe and highly effective. This study assessed the proportion of successfully vaccinated individuals among cases with acute hepatitis B, the proportion of preventable cases if individuals were vaccinated as recommended, and the reasons for failures. METHODS: We analyzed data reported to the Italian Surveillance System for Acute Viral Hepatitis from 1993 to 2014. RESULTS: A total of 362 of 11 311 (3.2%) cases with acute hepatitis B were vaccinated. Of the 277 cases for whom immunization data were available, 50 (18%) received a complete vaccination course according to the correct schedule and before exposure to hepatitis B virus. Molecular characterization of 17 of these cases showed that 6 were infected with S-gene mutants. Among the 10 949 unvaccinated cases, 213 (1.9%) escaped mandatory vaccination and 2821 (25.8%) were not vaccinated despite being at increased risk of infection. Among the latter, the most common risk factors were cohabitation with hepatitis B surface antigen (HBsAg) carriers, intravenous drug use, and homosexual/bisexual practices. Thirty-seven percent of the unvaccinated households with HBsAg carriers were aware of their risk. Lack of trust in the vaccination, negative attitude, and inaccurate beliefs followed by lack of or poor communication and low perceived severity of the disease were the most frequent reasons for vaccine hesitancy. CONCLUSIONS: Development of acute disease in successfully vaccinated individuals is a rare event. Further efforts are needed to enhance the vaccine coverage rate in individuals at increased risk of infection.

Clinical, epidemiological and virological features of acute hepatitis B in Italy.

PURPOSE: To evaluate the association of hepatitis B virus (HBV) genotypes, basal core promoter (BCP)/precore (PC) and S gene mutations with the clinical-epidemiological characteristics of acute hepatitis B (AHB) in Italy. METHODS: During July 2005-January 2007, 103 symptomatic AHB patients were enrolled and prospectively followed up at 15 national hospitals. HBV genotypes, BCP/PC and S gene variants were determined by nested-PCR and direct sequence analysis. RESULTS: Genotype D, A and F were detected in 49, 45 and 6% of patients, respectively. BCP, PC, and BCP plus PC variants were found in 3.1, 11.3 and 7.2% of patients, respectively. At enrollment, 68.3% of patients were hepatitis B e antigen (HBeAg)-positive and 31.7% HBeAg-negative. BCP/PC mutations were more common in HBeAg-negative than in HBeAg-positive patients (p < 0.0001). Compared to genotype D patients, those harboring non-D genotypes were more frequently males (p = 0.023), HBeAg-positive (p < 0.001), had higher bilirubin (p = 0.014) and viremia (p = 0.034) levels and less frequently carried BCP/PC mutations (p < 0.001). Non-D genotype patients more often were from Central Italy (p = 0.001) and reported risky sexual exposure (p = 0.021). Two patients had received vaccination before AHB: one harbored genotype F; the other showed a S gene mutation. Four patients developed fulminant AHB; mutations were found in 2 of 3 patients who underwent BCP/PC sequencing. After a 6-month follow-up, only 2 (2.8%) patients developed persistent infection. CONCLUSION: AHB by non-D genotypes is increasing in Italy and is associated with risky sexual exposure. The ability of some genotypes to cause persistent and/or severe infection in Italy warrants larger studies for clarification.

Surveillance of hepatitis A virus in urban sewages and comparison with cases notified in the course of an outbreak, Italy 2013.

BACKGROUND: Over the past 20 years, Hepatitis A notifications in Italy have been in decline. Since the beginning of 2013 however, Italy has been experiencing a foodborne hepatitis A outbreak caused by genotype IA, involving hundreds of cases. Consumption of frozen mixed berries was deemed the potential vehicle of infection.We aimed to investigate the spread of hepatitis A virus (HAV) in Italy through the monitoring of urban sewages collected at Wastewater Treatment Plants (WTPs) and a subsequent comparison of environmental surveillance data with data from the clinical surveillance performed during the epidemic. METHODS: The study covered 15 months, from July 2012 to September 2013, comprising the outbreak and the preceding six months. Environmental surveillance consisted of the analysis of urban sewage samples collected at 19 WTPs in seven of the Italian regions most affected by the epidemic. HAV isolates were detected and typed using a nested RT-PCR targeting the VP1/2A junction. Parallel clinical surveillance was performed by the sentinel surveillance system for acute viral hepatitis (SEIEVA) and by the ministerial Central Task Force on Hepatitis A, established with the purpose of determining the source of the outbreak and adopting appropriate outbreak control strategies. RESULTS: A total of 38/157 wastewater samples (24.2%) were positive for HAV, 16 collected in 2012 and 22 in 2013. Several HAV strains were detected, including the IA variant implicated in the outbreak and isolated from clinical cases over the same period. The vast majority of sequences belonged to genotype IB. Interestingly however, although these included variants related to strains that had been involved in past Italian epidemics, none were detected in recent clinical samples, probably due to underreporting or asymptomatic circulation. Conversely, a number of sequences were identified in clinical samples that were not found in wastewaters. CONCLUSIONS: The percentage of sewage samples detected as HAV-positive in this study are consistent with the classification of Italy as a country with low/intermediate endemicity. A combined environmental/clinical surveillance is able to provide a more complete picture of the spread of HAV and of the genotypes circulating in the population, allowing a better understanding of changes in disease trends.

Exploring COVID-19 Vaccination Willingness in Italy: A Focus on Resident Foreigners and Italians Using Data from PASSI and PASSI d'Argento Surveillance Systems.

(1) The COVID-19 pandemic exacerbated health disparities, both between foreign and autochthonous populations. Italy was one of the European countries that was the most affected by the COVID-19 pandemic; however, only limited data are available on vaccine willingness. This study aims to assess the propensity of foreign and autochthonous populations residing in Italy to be vaccinated and the relative associated factors. (2) Data were collected and analysed from the two Italian surveillance systems, PASSI and PASSI d'Argento, in the period of August 2020-December 2021. The data include those of the Italian resident adult population over 18 years old. A multinomial logistic regression model, stratified by citizenship, was used to assess the associations of sociodemographic, health, and COVID-19 experience variables with vaccination attitudes. (3) This study encompassed 19,681 eligible subjects. Considering the willingness to be vaccinated, foreign residents were significantly less certain to get vaccinated (49.4% vs. 60.7% among Italians). Sociodemographic characteristics, economic difficulties, and trust in local health units emerged as factors that were significantly associated with vaccine acceptance. Having received the seasonal flu vaccine was identified as a predictor of COVID-19 vaccine acceptance among foreign and Italian residents. (4) This study underscores the significance of tailoring interventions to address vaccine hesitancy based on the diverse characteristics of foreign and Italian residents. This research offers practical insights for public health strategies, highlighting the importance of tailored educational campaigns, improved communication, and nuanced interventions to enhance vaccine acceptance and uptake within both populations.

The Opportunity Provided by Vaccination Offer to Refugees from Ukraine in European Countries.

(1) The Russian invasion of Ukraine forced many people to leave their country and seek asylum in various European countries, with serious consequences from a health perspective. In this context, we describe the health measures undertaken by AcToVax4NAM Consortium Countries (Cyprus-Germany-Greece-Italy-Malta-Poland-Romania-Spain) to prevent Vaccine-Preventable Disease (VPD) outbreaks in the context of mass movements of populations that resulted from the crisis in Ukraine. (2) We collected information on the vaccinations offered to Ukrainians in the Consortium Countries. (3) All these countries have provided Temporary Protection (TP) status to refugees from Ukraine and have followed the recommendations of European and International Agencies to offer them vaccinations according to the National Immunisation Programmes. The COVID-19 vaccination is offered in all countries with regard to the general population. Most countries provide information on TP and access to health/vaccination services in the Ukrainian language. (4) The information collected shows a common effort to ensure the adequate planning of health and vaccination services for refugees from Ukraine and, very often, to include them in the national vaccination offer. It is important that this initial response towards people who have fled Ukraine will be continued following the emergency but, more importantly, that it serves as a best practice towards all migrants and refugees entering the EU.

Second Neoplasms in Italian Patients with Hairy Cell Leukemia after Treatment with Cladribine: A Multicenter Investigation and Literature Review.

Concern has emerged about the prevalence of second cancers among patients with hairy cell leukemia (HCL) treated with purine analogs. We investigated 513 patients with HCL treated with cladribine over the last 30 years at 18 Italian centers and calculated their standardized incidence ratios (SIRs). We identified 24 patients with a second cancer diagnosed at a median time from treatment with cladribine of 59.9 months (range: 9.2-169.7 months). All patients with solid neoplasms presented with a limited-stage disease, except four cases of locally advanced cancer; multiple myeloma patients had a smoldering disease, while lymphoma patients had stage Ie and stage IV diseases. Response to therapy was complete in 19 cases; 1 patient is still receiving treatment for a relapsing bladder disease, while 2 patients progressed during treatment and died. These two patients died from unrelated causes: one from infection and one due to surgery complications. The median OS from HCL was 98.5 months (range: 38.4-409.2 months), while the median OS from second cancer was 27.6 months (range: 1-117.8 months). The SIR was 0.86 (95% CI: 0.54-1.30) for males and 1.13 (95% CI: 0.36-2.73) for females: no statistically significant differences were highlighted. We were not able to demonstrate an excess of second cancer or a significant association with the specific studied neoplasm.

Prevalence of chronic HCV infection in EU/EEA countries in 2019 using multiparameter evidence synthesis.

Background: Epidemiological data are crucial to monitoring progress towards the 2030 Hepatitis C Virus (HCV) elimination targets. Our aim was to estimate the prevalence of chronic HCV infection (cHCV) in the European Union (EU)/European Economic Area (EEA) countries in 2019. Methods: Multi-parameter evidence synthesis (MPES) was used to produce national estimates of cHCV defined as: π = πrecρrec + πexρex + πnonρnon; πrec, πex, and πnon represent cHCV prevalence among recent people who inject drugs (PWID), ex-PWID, and non-PWID, respectively, while ρrec, ρex, and ρnon represent the proportions of these groups in the population. Information sources included the European Centre for Disease Prevention and Control (ECDC) national operational contact points (NCPs) and prevalence database, the European Monitoring Centre for Drugs and Drug Addiction databases, and the published literature. Findings: The cHCV prevalence in 29 of 30 EU/EEA countries in 2019 was 0.50% [95% Credible Interval (CrI): 0.46%, 0.55%]. The highest cHCV prevalence was observed in the eastern EU/EEA (0.88%; 95% CrI: 0.81%, 0.94%). At least 35.76% (95% CrI: 33.07%, 38.60%) of the overall cHCV prevalence in EU/EEA countries was associated with injecting drugs. Interpretation: Using MPES and collaborating with ECDC NCPs, we estimated the prevalence of cHCV in the EU/EEA to be low. Some areas experience higher cHCV prevalence while a third of prevalent cHCV infections was attributed to PWID. Further efforts are needed to scale up prevention measures and the diagnosis and treatment of infected individuals, especially in the east of the EU/EEA and among PWID. Funding: ECDC.

A holistic evaluation of patients with chronic Hepatitis D virus (HDV) infection enrolled in the Italian PITER-B and delta cohort.

BACKGROUND AND AIMS: We aimed to characterize the epidemiologic and comorbidities profiles of patients with chronic Hepatitis D (CHD) followed in clinical practice in Italy and explored their interferon (IFN) eligibility. METHODS: This was a cross-sectional study of the PITER cohort consisting of consecutive HBsAg-positive patients from 59 centers over the period 2019-2023. Multivariable analysis was performed by logistic regression model. RESULTS: Of 5492 HBsAg-positive enrolled patients, 4152 (75.6%) were screened for HDV, 422 (10.2%) were anti-HDV positive. Compared with HBsAg mono-infected, anti-HDV positive patients were more often younger, non-Italians, with a history of drug use, had elevated alanine transaminase (ALT), cirrhosis, or hepatocellular carcinoma (HCC). Compared with Italians, anti-HDV positive non-Italians were younger (42.2% age ≤ 40 years vs. 2.1%; P < 0.001), more often females (males 43.0% vs. 68.6%; P < 0.001) with less frequent cirrhosis and HCC. HDV-RNA was detected in 63.2% of anti-HDV-positive patients, who were more likely to have elevated ALT, cirrhosis, and HCC. Extrahepatic comorbidities were present in 47.4% of anti-HDV positive patients and could affect the eligibility of IFN-containing therapies in at least 53.0% of patients in care. CONCLUSIONS: CHD affects young, foreign-born patients and older Italians, of whom two-thirds had cirrhosis or HCC. Comorbidities were frequent in both Italians and non-Italians and impacted eligibility for IFN.

Local radiotherapy and measurable residual disease-driven immunotherapy in patients with early-stage follicular lymphoma (FIL MIRO): final results of a prospective, multicentre, phase 2 trial.

BACKGROUND: The mainstay of treatment for early-stage follicular lymphoma is local radiotherapy, with a possible role for anti-CD20 monoclonal antibody (mAb). We aimed to evaluate the effect of these treatments using a measurable residual disease (MRD)-driven approach. METHODS: This prospective, multicentre, phase 2 trial was conducted at 27 centres of the Fondazione Italiana Linfomi (FIL) in Italy. Eligible participants were adults (≥18 years) with newly diagnosed, histologically confirmed follicular lymphoma (stage I or II; grade I-IIIa). Patients were initially treated with 24 Gy involved-field radiotherapy over 12 days; those who were MRD-positive after radiotherapy or during follow-up received eight intravenous doses (1000 mg per dose; one dose per week) of the anti-CD20 mAb ofatumumab. The primary endpoint was the proportion of patients who were MRD-positive after involved-field radiotherapy and became MRD-negative after ofatumumab treatment. Patients were included in the primary endpoint analysis population if they were positive for BCL2::IGH rearrangement at enrolment in peripheral blood or bone marrow samples. MRD positivity was defined as the persistence of BCL2::IGH rearrangement in peripheral blood or bone marrow, assessed centrally by laboratories of the FIL MRD Network. The trial was registered with EudraCT, 2012-001676-11. FINDINGS: Between May 2, 2015, and June 1, 2018, we enrolled 110 participants, of whom 106 (96%) were eligible and received involved-field radiotherapy. Of these, 105 (99%) were White, one (1%) was Black, 50 (47%) were male, and 56 (53%) were female. Of 105 participants in whom BCL2::IGH status was evaluable, 32 (30%) had a detectable BCL2::IGH rearrangement at baseline. After radiotherapy, 12 (40%) of 30 patients reached MRD-negative status, which was long-lasting (at least 36 or 42 months) in three (25%). In those who were MRD-positive after radiotherapy, ofatumumab induced MRD-negativity in 23 (92%; 95% CI 74-99) of 25 evaluable patients. After a median follow-up of 46·1 months (IQR 42·8-50·8), 14 (61%) of these 23 patients remain in complete response and are MRD-negative. The most common grade 3-4 adverse events were infusion-related reactions, observed in four patients. INTERPRETATION: Local radiotherapy is frequently not associated with the eradication of follicular lymphoma. An MRD-driven, anti-CD20 monoclonal antibody consolidation enables molecular remission to be reached in almost all patients and is associated with a reduced incidence of relapse over time. A clinical advantage of an MRD-driven consolidation is therefore suggested. FUNDING: AIRC Foundation for Cancer Research in Italy, Novartis International, and GlaxoSmithKline.

Role of IL28B gene polymorphism and cell-mediated immunity in spontaneous resolution of acute hepatitis C.

BACKGROUND: A single-nucleotide polymorphism (SNP; rs12979860) near the IL28B gene has been associated with spontaneous and treatment-induced hepatitis C virus clearance. We investigated predictors of spontaneous disease resolution in a cohort of patients with acute hepatitis C (AHC), analyzing epidemiological, clinical and virological parameters together with IL28B.rs12979860 genotypes and cell-mediated immunity (CMI). METHODS: Fifty-six symptomatic AHC patients were enrolled and followed prospectively. CMI was measured in 31 patients at multiple time points by interferon-γ enzyme-linked immunospot assay and was correlated to the IL28B.rs12979860 SNP. RESULTS: Eighteen patients had a self-limiting AHC that was associated with female sex (P = .028), older age (P = .018), alanine aminotransferase level >1000 U/L (P = .027), total bilirubin level >7 mg/dL (P = .036), and IL28B.rs12979860 genotype CC (P = .030). In multivariate analysis, only CC genotype was independently associated with self-limiting AHC (odds ratio, 5.3; 95% confidence interval, 1.1-26.5). Patients with the CC genotype with self-limiting AHC had a stronger (P = .02) and broader (P = .013) CMI than patients with the CT genotype with chronically evolving AHC. In patients with chronically evolving disease, CC genotype was associated with a broader CMI compared to CT genotype (P = .028). A negative CMI was more frequently associated with CT genotype among persistently infected patients (P = .043) and with persistent infection among CT patients (P = .033). CONCLUSIONS: . Self-limiting AHC was independently associated with CC genotype. The correlation between IL28B.rs12979860 genotypes and CMI is suggestive of a possible important role of CMI in favoring hepatitis C virus clearance in CC patients.

Risk factors for and incidence of acute hepatitis C after the achievement of blood supply safety in Italy: results from the national surveillance system.

Surveillance systems for acute hepatitis C allow monitoring of disease incidence trends and transmission patterns. This study aimed to describe the epidemiological profile of reported cases of symptomatic acute hepatitis C in Italy after the achievement of blood supply safety. The incidence of symptomatic acute hepatitis C since 1991 was estimated. Risk factors for acute hepatitis C were analyzed for the period 2003-2010 through a case-control study within a population-based surveillance for acute viral hepatitis. From 1991 to 2010, the incidence decreased from 2 to 0.2 per 100,000, with a more evident decrease among persons aged 15-24 years. During 2003-2010, 1,053 cases were reported. Intravenous drug use (adjusted odds ratio [(adj) OR], 30.5; 95% confidence interval [CI], 18.9-49.1), cohabitation or sexual partnership with an hepatitis C virus (HCV) carrier ((adj) OR, 11.2; 95% CI, 6.6-19.2), nosocomial exposure ((adj) OR, 6.6; 95% CI, 4.6-9.4); unsafe sexual practices ((adj) OR, 3.1; 95% CI, 1.9-5.2), and cosmetic treatments with percutaneous exposure ((adj) OR, 1.7; 95% CI, 1.2-2.4) were independently associated with acute hepatitis C. Population attributable risk estimates indicated nosocomial exposure (39.6%) and intravenous drug use (30.5%) as responsible for most cases. In conclusion, the incidence of symptomatic acute hepatitis C is declining in Italy. Currently, the most important risk factors are: having an HCV-positive household or sexual partner, unsafe sexual practices, cosmetic percutaneous treatments, intravenous drug use, and nosocomial exposure; the latter two factors are responsible for most cases. Effective prevention programs for intravenous drug users and strict adherence to universal precautions in healthcare settings are needed.

Clinical and organizational impact of the use of different cardiac troponin assays for the diagnosis of myocardial infarction without persistent elevation of the ST segment at presentation (NSTEMI) in 12 Italian emergency departments (EDs): the TROCAR study.

The management of acute chest pain is one of the challenges for emergency departments (EDs) worldwide. This study aims to provide insights into clinical and organizational aspects related to the use of different cardiac troponin tests for the diagnosis of NSTEMI. A prospective observational study was conducted among 12 Italian EDs. Eligible participants had chest pain of suspected cardiac origin and accessed EDs from January 2017 to March 2019. A 30-day follow-up was performed to gather information about the main cardiac outcomes. Tests validity and performance were assessed by computing sensitivity, specificity, positive and negative predictive values and area under the ROC curve. The independent association between adverse event end point at 30 days and type of troponin was evaluated by multiple logistic regression models, using odds ratio and 95% confidence interval. 2913 patients were included. Almost 72% were affected by comorbidities and most of them stayed in the EDs for more than 3 h, with significant differences among the different troponin assays. The results of follow-up at 30 days for the outcomes considered for the patients who were ruled out in 3 h or less did not differ significantly compared to those ruled out after 3 h or more. After adjustment for confounders, patients admitted to an ED that used a high-sensitivity troponin were at a lower risk of having a MACE (OR = 0.53, 95%CI 0.35-0.90) and a non-significant lower risk of myocardial infarction (OR = 0.68, 95% CI 0.41-1.13, p = 0.1314) at 30 days compared to patients admitted to an ED that used a standard troponin. Appropriate troponin testing is extremely important for differential diagnosis and for addressing proper treatment and safe procedures for patients who are not admitted to the hospital.