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

Background: Machine learning can operationalize the rich and complex data in electronic patient records for exploratory pharmacovigilance endeavours.Objective: The objective of this review is to identify applications of machine learning and big patient data in exploratory pharmacovigilance.Methods: We searched PubMed and Embase and included original articles with an exploratory pharmacovigilance purpose, focusing on medicinal interventions and reporting the use of machine learning in electronic patient records with ≥1000 patients collected after market entry.Findings: Of 2557 studies screened, seven were included. Those covered six countries and were published between 2015 and 2021. The most prominent machine learning methods were random forests, logistic regressions, and support vector machines. Two studies used artificial neural networks or naive Bayes classifiers. One study used formal concept analysis for association mining, and another used temporal difference learning. Five studies compared several methods against each other. The numbers of patients in most data sets were in the order of thousands; two studies used what can more reasonably be considered big data with >1 000 000 patients records.Conclusion: Despite years of great aspirations for combining machine learning and clinical data for exploratory pharmacovigilance, only few studies still seem to deliver somewhat on these expectations.

Coronavirus-disease-2019 (COVID-19) mRNA vaccination effectively reduces mortality and morbidity in cirrhotic patients, but the immunogenicity and safety of vaccination have been partially characterized. The study aimed to evaluate humoral response, predictive factors, and safety of mRNA-COVID-19 vaccination in cirrhotic patients compared to healthy subjects. A prospective, single-center, observational study enrolled consecutive cirrhotic patients who underwent mRNA-COVID-19 vaccination from April to May 2021. Anti-spike-protein (anti-S) and nucleocapsid-protein (anti-N) antibodies were evaluated before the first (T0) and the second (T1) doses and 15 days after completing the vaccination. An age and sex-matched healthy reference group was included. The incidence of adverse events (AEs) was assessed. In total, 162 cirrhotic patients were enrolled, 13 were excluded due to previous SARS-CoV-2 infection; therefore, 149 patients and 149 Health Care Workers (HCWs) were included in the analysis. The seroconversion rate was similar in cirrhotic patients and HCWs at T1 (92.5% vs. 95.3%, p = 0.44) and T2 (100% in both groups). At T2, anti-S-titres were significantly higher in cirrhotic patients compared to HCWs (2776.6 vs. 1756 BAU/mL, p < 0.001]. Male sex (β = −0.32 [−0.64, −0.04], p = 0.027) and past-HCV-infection (β = −0.31 [−0.59, −0.04], p = 0.029) were independent predictors of lower anti-S-titres on multiple-gamma-regression-analysis. No severe AEs occurred. The COVID-19-mRNA vaccination induces a high immunization rate and anti-S-titres in cirrhotic patients. Male sex and past-HCV infection are associated with lower anti-S-titres. The COVID-19-mRNA vaccination is safe.

Background: The recent resurgence of mpox in central Africa has been declared a new public health emergency of international concern (PHEIC) requiring coordinated international responses. Vaccination is a priority to expand protection and enhance control strategies, but the vaccine’s need exceeds the currently available doses. Intradermal (ID) administration of one-fifth of the standard modified vaccinia Ankara (MVA-BN) dose was temporarily authorized during the 2022 PHEIC. Studies conducted before 2022 provided evidence about the humoral response against the vaccinia virus (VACV) after vaccination but not against the mpox virus (MPXV). Moreover, no data are available on the T-cell response elicited by MVA-BN administered subcutaneously or intradermally. Methods: We compare the two vaccine administration routes according to reactogenicity (n = 943) and immunogenicity (n = 225) of vaccine recipients attending INMI Spallanzani hospital during the 2022 vaccination campaign in Rome, Italy. Results: We found that the ID route elicited higher titers of MPXV-specific IgG (mean difference of 0.26 log₂, p = 0.05) and nAbs (0.24 log₂, p = 0.08) than the subcutaneous (SC) route one month after the complete vaccination cycle. At the same time, no evidence for a difference in cellular response was found. Conclusions: MVA-BN was globally well tolerated despite higher reactogenicity for the ID than the SC route, especially for the reactions at the local injection site. The ID dose-sparing strategy was proven safe and immunogenic and would make vaccination available to more people. Our data support the current WHO recommendation of using the ID route in low–medium-income countries (LMIC), although response data in people infected with the new 1b clade are urgently needed.

Solid organ transplant recipients (SOTRs) are at high risk of severe coronavirus disease 2019 (COVID-19), therefore early treatment of mild infections is crucial to prevent increased morbidity and mortality. The effectiveness of early treatment in SOTRs has yet to be fully characterized due to the emergence of new SARS-CoV-2 variants and to COVID-19 vaccination implementation. The aim of this single-center retrospective study is to evaluate the outcomes, safety and impact on SARS-CoV-2 viral load kinetics of COVID-19 early treatment in SOTRs. The study includes 80 SOTRs with a laboratory-confirmed diagnosis of symptomatic SARS-CoV-2 infection enrolled between January and October 2022 and treated with either monoclonal antibodies or antivirals. All patients received COVID-19 vaccination and 68.8% of them showed detectable levels of anti-spike (S) antibodies. The occurrence of clinical events (hospitalization, intensive care unit admission, or death) was assessed within 30 days after treatment initiation. The quantification of SARS-CoV-2 viral load were performed at baseline and at day-7. The rate of hospitalization was 2.5% [0.3–9%] and no deaths occurred. All patients completed treatment with no serious adverse events. Median viral load decrease was 0.48 [0.26–0.69] log₂ cycle threshold (ct) values, with no significant differences between SOTRs treated with monoclonal antibodies and those treated with antivirals. Viral load decrease was significantly associated with positive anti-s serology at baseline ($\beta$ = 0.196, p = 0.01), number of days between symptom onset and treatment ($\beta$ = 0.05, p = 0.03) and the number of comorbidities ($\beta$ = −0.05, p = 0.03). We provide evidence of real-world effectiveness of early therapy in SOTRs infected with SARS-CoV-2 and demonstrate the relevant role of humoral response to vaccination in enhancing early viral load decay during treatment.

Background/Objectives: HCV prevalence among men who have sex with men (MSM) is not negligible, but information in Italy is scarce, particularly for HIV-uninfected MSM. We report data from an HCV screening program targeted to MSM in Rome started in 2019 in two hospital settings and in four urban community-based (CB) settings run by NGOs. Methods: Adult MSM (>18 years old) presenting for HIV or Sexually transmitted infection testing or attending CB activities, have been invited to undergo, after providing informed consent, a free-of-charge rapid HCV Antibody test (OraQuick HCV®). For all participants, demographic, clinical and behavioural data using an anonymous questionnaire were collected. Free confirmatory standard serology tests were offered for those found reactive at rapid HCV test and then individuals with confirmed chronic HCV-infection, were referred though a dedicated “fast track” pathway for further clinical and laboratory assessment and DAA-treatment according to the national treatment guidelines. Results: From July 2019 and July 2023, 2.714 MSM agreed to be screened for HCV infection. Median age was 36 years (IRQ=29-46), 91.0% were Italians, 58,0% enrolled in the two clinical centers and 10,7% reported to be person living with HIV (PLWH). Overall, 9 (0,33%) MSM were found to be reactive for HCV-Ab at rapid test. Eight MSM were retested and 7 were confirmed as having chronic HCV infection (HCV viremia range: 8x103-23x106 IU/mL). The prevalence of confirmed cases was 0.26% (7/2,714; 95%CI: 0.10-0.53), higher in PLWH compared to those not reporting HIV infection (1.04% vs. 0.17, p=0.03). High-risk behaviours for HCV infection and/or history of Sexual Transmitted infection (STI) were recorded in all HCV confirmed cases. All seven persons were linked to care, clinically assessed and started DAA treatment, with sustained viral response (SVR) in all cases. Conclusions: These data suggest feasibility and potential effectiveness of a preventive program targeting MSM living in Rome, which combines HCV screening, case finding and linkage to prompt care. HCV-prevalence in the screened population, however, was quite low, although it is significantly higher in PLWH and in those with high-risk behaviours, suggesting that targeted screening of PLWH and individuals with high-risk behaviours may be more effective to achieve HCV eradication than universal screening.