Background: LC has been associated with hyporesponsiveness to several vaccines. Nonetheless, no data on complete serological and B- and T-cell immune response are currently available. Aims: To assess, in comparison with healthy controls of the same age and gender, both humoral and cellular immunoresponses of patients with LC after two or three doses of the mRNA Pfizer-BioNTech vaccine against SARS-CoV-2 and to investigate clinical features associated with non-response. Material and methods: 179 patients with LC of CTP class A in 93.3% and viral etiology in 70.1% of cases were longitudinally evaluated starting from the day before the first dose to 4 weeks after the booster dose. Their antibody responses were compared to those of healthcare workers without co-morbidities. In a subgroup of 40 patients, B- and T-cell responses were also compared to controls. Results: At d31, d90 and d180 after BNT162b2 vaccine, no detectable SARS-CoV-2 IgG response was observed in 5.9%, 3.9% and 7.2% of LC patients as compared to 0 controls (p < 0.03). A delay in B-cell and lack of prompt T-cell response compared to healthcare workers was also registered. A significant correlation between antibody titers and cellular response was observed. A MELD score > 8 was the only independent predictor of poor d31 response (p = 0.028). Conclusions: Our results suggest that cirrhotic patients have a slower and in <10% suboptimal immune response to SARS-CoV-2 vaccination. Rates of breakthrough infections were comparable between cirrhotics and controls. The booster dose was critical in inducing both humoral and cellular responses comparable to controls.

In 2023, the Italian healthcare system launched HCV screening targeting subjects born in 1968–1989. However, subjects > 50 yrs also need screening. In addition, existence of gender gaps in HCV diagnosis and treatment has been suggested. Our aim was to identify undiagnosed individuals outside the age groups to whom the screening is offered and to gather data about gender gaps. This is a prospective, opportunistic micro-elimination initiative based on a network between 24 Apulian pharmacies and our center. Between 01/07/2022 and 01/03/2024, subjects aged 55 to 85, accessing pharmacies were offered HCVOraQuick tests (F/M 1:1) and administered ad-hoc questionnaires. In total, 13,042 screening were carried out. Mean age was 64.9 (± 7.6), 51.1% females. Overall, 1.1% were anti-HCV positive: mean age 68.3 (± 10.3), 44.9% females. Seroprevalence was higher in males (p < 0.00001), elderly (p < 0.00001) and unknown transmission route (p = 0.0009). HCV-RNA was detectable in 67.4% of seropositive. They were 67.5 (± 10.7) yrs old, mainly males (55.1%). HCV-RNA prevalence was 0.8%, higher in elderly (p = 0.0003) and unknown transmission route (p = 0.0007). Overall, 90% were linked-to-treatment. Differences in patients profiles should be considered to guide policy and more inclusive treatment approaches. Gender differences in screening response and rates of active infections underscore the need for gender-targeted intervention.

Introduction: Hepatitis C virus (HCV) infection often coexists with comorbidities, increasing vulnerability, complications, and adverse events. Direct-acting antivirals (DAAs) have dramatically improved HCV management, but they differ in drug–drug interaction (DDI) profiles. Sofosbuvir/velpatasvir (SOF/VEL) is associated with minimal clinically relevant interactions. Areas covered: A narrative review of the literature was conducted by searching PubMed and major international guidelines, focusing on studies published in the DAA era addressing HCV patients with major comorbidities, focusing on diabetes, metabolic syndrome, and cardiovascular disease; neuropsychiatric disorders; cancer; transplants; and use of substances or treatment with opioid agonists; and patients requiring hormone therapy including transgender patients. Expert opinion: Based on the literature and real-world data, managing polypharmacy in HCV patients with comorbidities is effective and well-tolerated, provided thorough drug review, potential DDI analysis, proactive monitoring, and coordinated multidisciplinary care are ensured. DAAs have dramatically improved the management of HCV patients; however, they have different DDI profiles that should be carefully checked. SOF/VEL has been shown to be associated with minimal clinically relevant interactions and offers a simple dosing regimen. DAA treatment is strongly advised in HCV comorbid patients not only to cure HCV but also to improve the course of comorbidities, provided that DDIs are no longer considered mere minor details.

Direct-acting antiviral therapies can cure most people with hepatitis C virus (HCV) infection with little need for testing or monitoring. A major challenge to eliminating HCV is ensuring patients complete all steps of care, including confirmation of cure. We assessed the concordance of sustained virologic response (SVR) at 4 weeks (SVR4) and 12 weeks (SVR12) post-treatment to evaluate the viability of SVR4 as a predictor of cure in patients treated with sofosbuvir (SOF)/velpatasvir (VEL). We conducted a retrospective analysis of patients from the Phase 3 ASTRAL-1, -2, and -3 programs and a historical cohort from the Louisiana Department of Health Sexually Transmitted Infection (STI)/HIV/Hepatitis Program claims database. Concordance analyses were performed for patients with both SVR4 and SVR12 data. The concordance analysis in the ASTRAL studies included 1015 patients; 1005 and 1002 achieved SVR4 and SVR12, respectively. Among SVR4 achievers, 3 failed to maintain SVR12, while all (10/10) patients who did not achieve SVR4 also failed SVR12. In the real-world cohort, 479/509 (94%) patients achieved SVR4 and 485/509 (95%) achieved SVR12. Of those with SVR4, 7 failed SVR12; 17 of 30 patients who did not achieve SVR4 also failed SVR12. High concordance between SVR4 and SVR12 was observed in both ASTRAL and the real-world dataset, supporting the use of SVR4 as a predictor of long-term SVR in patients with HCV infection treated with SOF/VEL. Streamlining cure confirmation by shifting SVR determination from week 12 to week 4 post-treatment may reduce patient loss to follow-up.

Introduction: Hepatitis C virus (HCV) infection often coexists with comorbidities, increasing vulnerability, complications, and adverse events. Direct-acting antivirals (DAAs) have dramatically improved HCV management, but they differ in drug–drug interaction (DDI) profiles. Sofosbuvir/velpatasvir (SOF/VEL) is associated with minimal clinically relevant interactions. Areas covered: A narrative review of the literature was conducted by searching PubMed and major international guidelines, focusing on studies published in the DAA era addressing HCV patients with major comorbidities, focusing on diabetes, metabolic syndrome, and cardiovascular disease; neuropsychiatric disorders; cancer; transplants; use of substances or treatment with opioid agonists; patients requiring hormone therapy including transgenders. Expert opinion: Based on literature and real-world data, managing polypharmacy in HCV patients with comorbidities is effective and well tolerated, provided thorough drug review, potential DDI analysis, proactive monitoring, and coordinated multidisciplinary care are ensured. DAAs have dramatically improved the management of HCV patients, however they have different DDI profiles that should be carefully checked. SOF/VEL has been shown to be associated with minimal clinically relevant interactions and offers a simple dosing regimen. DAA treatment is strongly advised in HCV comorbid patients not only to cure HCV but also to improve the course of comorbidities, provided that DDIs are no longer considered mere minor details.