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Hepatitis D virus (HDV) infection remains a significant global health challenge due to its severity and high risk of progression to cirrhosis and hepatocellular carcinoma (HCC). Bulevirtide, a novel HDV entry inhibitor, has shown promise in managing chronic hepatitis D by blocking viral entry into hepatocytes. This study evaluated the efficacy and safety of bulevirtide in reducing HDV RNA levels and improving liver function in a real-life cohort of Italian patients with HDV infection. This multicenter prospective trial enrolled 85 consecutive patients with chronic HDV infection, from June 2023 to June 2024, who received 2 mg/day of bulevirtide as monotherapy or in combination with a nucleoside/nucleotide analogue for hepatitis B virus (HBV) infection. Patients with any stage of liver fibrosis or compensated cirrhosis were included. Data collected included demographic and clinical characteristics, liver function tests, HDV RNA levels, and adverse events at baseline and 6 months. The virological response was achieved in 55.7% of patients (n=47), with 32 demonstrating undetectable HDV RNA levels. Among responders, ALT levels decreased significantly from 66.0 U/mL (IQR 46.5–120.0) to 31.5 U/mL (IQR 25.0–37.0, p < 0.001), and AST levels from 71.0 U/mL (IQR 48.5–94.5) to 31.0 U/mL (IQR 27.0–38.5, p = 0.021). Median HDV RNA dropped from 16,410 IU/mL (IQR 2,530–339,400) to 0 IU/mL (IQR 0–84,000, p < 0.001). No significant predictors of response emerged. Mild adverse events, including pruritus (7.1%) and injection-site reactions (2.4%), were reported, with no treatment discontinuation. Bulevirtide effectively reduces HDV RNA levels and improves liver function with a favorable safety profile, offering a promising therapeutic option for chronic hepatitis D. Further large-scale studies are needed to confirm these findings and explore long-term outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Hepatitis D virus (HDV) infection remains a significant global health challenge due to its severity and high risk of progression to cirrhosis and hepatocellular carcinoma (HCC). Bulevirtide, a novel HDV entry inhibitor, has shown promise in managing chronic hepatitis D by blocking viral entry into hepatocytes. This study evaluated the efficacy and safety of bulevirtide in reducing HDV RNA levels and improving liver function in a real-life cohort of Italian patients with HDV infection., Methods: This multicenter prospective trial enrolled 108 consecutive patients with chronic HDV infection, from June 2023 to June 2024, who received 2 mg/day of bulevirtide in combination with a nucleoside/nucleotide analogue for hepatitis B virus (HBV) infection. Patients with any stage of liver fibrosis or compensated cirrhosis were included. Data collected included demographic and clinical characteristics, liver function tests, HDV RNA levels, and adverse events at baseline and 6 months., Results: The virological response was achieved in 54.6% of patients ( n = 59), with 36 demonstrating undetectable HDV RNA levels. Among responders, ALT levels decreased significantly from 67.0 U/mL [IQR 44.0-116.3] to 31.5 U/mL [IQR 24.0-36.5, p = 0.001], and AST levels from 66.0 U/mL [IQR 46.5-91.0] to 32.5 U/mL [IQR 28.0-38.0, p = 0.021]. Median HDV RNA dropped from 29,800 IU/mL [IQR 3100-375,000] to 0 IU/mL [IQR 0-291, p < 0.001]. No significant predictors of response emerged. Mild adverse events, including pruritus (5.6%) and injection-site reactions (1.9%) and flu-like syndrome (0.9) were reported, with no treatment discontinuation., Conclusions: Bulevirtide effectively reduces HDV RNA levels and improves liver function with a favorable safety profile, offering a promising therapeutic option for chronic hepatitis D. Further large-scale studies are needed to confirm these findings and explore long-term outcomes.

Background: Sepsis still represents a major public health issue worldwide, and the immune system plays a main role during infections; therefore, its activity is mandatory to resolve this clinical condition. In this report, we aimed to retrospectively verify in a real-life setting the possible usefulness of pentameric IgM plus antibiotics in recovering patients with sepsis after major abdominal surgery., Materials/methods: We reviewed, from January 2013 until December 2019, all adult patients admitted to the ICU for sepsis or septic shock (2) after major abdominal surgery. Among these patients, were identified those that, according to legal indication and licenses in Italy, were treated with pentameric IgM plus antibiotics (Group A) or with antibiotics alone (Group B). The following parameters were evaluated: blood gas analysis, lactate, CRP, procalcitonin, endotoxin activity, liver and renal function, coagulation and blood cell count at different time points (every 48 h for at least 7 days). Differences between groups were analyzed using Fisher's exact test or a chi-square test for categorical variables. A Mann-Whitney U test or Kruskal-Wallis test were instead been performed to compare continuous variables. Univariate and multivariate analysis were also performed., Results: Over a period of 30 months, 24 patients were enrolled in Group A and 20 patients in Group B. In those subjects, no statistical differences were found in terms of bacterial or fungal infection isolates, when detected in a blood culture test, or according to inflammatory index, a score, lactate levels and mortality rate. A 48 h response was statistically more frequent in Group B than in Group A, while no differences were found in other clinical and laboratory evaluations., Conclusions: Based on our results, the use of pentameric IgM does not seem to give any clinical advantages in preventing sepsis after major abdominal surgery., Competing Interests: The authors declare no conflict of interest.

Tixagevimab-cilgavimab is effective for the treatment of early COVID-19 in outpatients with risk factors for progression to severe illness, as well as for primary prevention and post-exposure prophylaxis. We aimed to retrospectively evaluate the hospital stay (expressed in days), prognosis, and negativity rate for COVID-19 in patients after treatment with tixagevimab-cilgavimab. We enrolled 42 patients who were nasal swab-positive for SARS-CoV-2 (antigenic and molecular)-both vaccinated and not vaccinated for COVID-19-hospitalized at the first division of the Cotugno Hospital in Naples who had received a single intramuscular dose of tixagevimab-cilgavimab (300 mg/300 mg). All patient candidates for tixagevimab-cilgavimab had immunocompromised immune systems either due to chronic degenerative disorders (Group A: 27 patients) or oncohematological diseases (Group B: 15 patients). Patients enrolled in group A came under our observation after 10 days of clinical symptoms and 5 days after testing positivite for COVID-19, unlike the other patients enrolled in the study. The mean stay in hospital for the patients in Group A was 21 ± 5 days vs. 25 ± 5 days in Group B. Twenty patients tested negative after a median hospitalization stay of 16 days (IQR: 18-15.25); of them, five (25%) patients belonged to group B. Therefore, patients with active hematological malignancy had a lower negativization rate when treated 10 days after the onset of clinical symptoms and five days after their first COVID-19 positive nasal swab.

Introduction: Real-world safety studies can provide important evidence on the thromboembolic risk associated with COVID-19 vaccines, considering that millions of people have been already vaccinated against COVID-19. In this study, we aimed to estimate the incidence of thromboembolic events after COVID-19 vaccination and to compare the Oxford-AstraZeneca vaccine with other COVID-19 vaccines., Methods: We conducted a retrospective real-world safety study using data from two different data sources: the Italian Pharmacovigilance database (Rete Nazionale di Farmacovigilanza, RNF) and the Campania Region Health system (Sistema INFOrmativo saNità CampanIA, SINFONIA). From the start date of the COVID-19 vaccination campaign (27 December 2021) to 27 September 2022, information on COVID-19 vaccinations and thromboembolic events were extracted from the two databases. The reporting rate (RR) and its 95% confidence interval (95%CI) of thromboembolic events for 10,000 doses was calculated for each COVID-19 vaccine. Moreover, the odds of being vaccinated with the Oxford-AstraZeneca vaccine vs. the other COVID-19 vaccines in cases with thromboembolic events vs. controls without thromboembolic events were computed., Results: A total of 12,692,852 vaccine doses were administered in the Campania Region, of which 6,509,475 (51.28%) were in females and mostly related to the Pfizer-BioNtech vaccine (65.05%), followed by Moderna (24.31%), Oxford-AstraZeneca (9.71%), Janssen (0.91%), and Novavax (0.02%) vaccines. A total of 641 ICSRs with COVID-19 vaccines and vascular events were retrieved from the RNF for the Campania Region, of which 453 (70.67%) were in females. Most ICSRs reported the Pfizer-BioNtech vaccine (65.05%), followed by Oxford-AstraZeneca (9.71%), Moderna (24.31%), and Janssen (0.91%). A total of 2451 events were reported in the ICSRs (3.8 events for ICSRs), of which 292 were thromboembolic events. The higher RRs of thromboembolic events were found with the Oxford-AstraZeneca vaccine (RR: 4.62, 95%CI: 3.50-5.99) and Janssen vaccine (RR: 3.45, 95%CI: 0.94-8.82). Thromboembolic events were associated with a higher likelihood of exposure to the Oxford-AstraZeneca vaccine compared to Pfizer-BioNtech (OR: 6.06; 95%CI: 4.22-8.68) and Moderna vaccines (OR: 6.46; 95%CI: 4.00-10.80)., Conclusion: We observed a higher reporting of thromboembolic events with viral-vector-based vaccines (Oxford-AstraZeneca and Janssen) and an increased likelihood of being exposed to the Oxford-AstraZeneca vaccine compared to the mRNA vaccines (Pfizer-BioNtech and Moderna) among thromboembolic cases.

The ESCMID-EUCIC guideline on decolonization of multidrug-resistant Gram-negative bacteria carriers does not recommend routine decolonization and highlights the necessity of well-powered and designed randomized clinical trials. Based on this limited evidence, we decided to conduct a scoping review with the aim of describing and discussing the last published studies investigating the efficacy and safety of decolonization therapies in drug-resistant Enterobacteriaceae carriers. Studies published in PubMed from January 1, 2017 to December 28, 2021 were retrieved. A PICO (population, intervention, comparator, outcome) framework was used for article selection as follows: Population defined as any patient of any age in any setting with screening sample yielding for drug-resistant Enterobacteriaceae; Intervention defined as any decolonization; Controls defined as patients receiving no intervention (spontaneous decolonization) or a different decolonization therapy; Outcomes defined as a microbiological, clinical, epidemiological and adverse event. A total of 679 records were initially identified, of which 647 were excluded because they were not related to decolonization therapies. Other 18 records were excluded because not related to our aims, target bacteria, or study design. A total of 12 clinical studies were included, of which 4 were randomized clinical trials and 8 were non-randomized studies. The majority of studies evaluated selective decontamination of the digestive tract or selective oropharyngeal decontamination regimens. Selected studies were characterized by high heterogeneity. Further high-quality studies with proper design and sample size calculation are warranted., Competing Interests: Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Due to the COVID-19 pandemic, all countries with a global mobilization started to produce and authorize vaccines, prioritizing healthcare professionals (HCPs) to reduce transmission. The aim of this study was to assess post-vaccination infections' occurrence among HCPs and their correlation with symptom onset. A retrospective cohort study was carried out in the Campania Region from December 2020 to April 2021. Data were retrieved from the Regional Health Information System of the Campania Region (Sinfonia). The study cohort included subjects that had all received at least one vaccine dose. Risk ratios (RRs) adjusted for age and sex (95% confidence intervals) were performed to assess differences in the prevalence between HCPs who tested positive or negative for COVID-19. Univariate and multivariate logistic regression models were used to evaluate the association between symptoms and vaccination status. Findings revealed that HCPs had a lower risk of contracting COVID-19 after receiving at least one vaccine dose, and this risk decreased with age. Furthermore, not having full vaccination coverage may predict a severe/critical evolution of the disease. This study provides a snapshot of the initial state of the Italian vaccination campaign on HCPs. A surveillance approach using Big Data matched to clinical conditions could offer a real analysis in the categorization of subjects most at risk.

Mutations in the ATP1A3 gene encoding the α3 subunit of Na+/K+-ATPase are associated with different neurological manifestations that may be elicited by febrile episodes. A recently described phenotype, linked to the p.Arg756Cys mutation, is clinically characterized by Relapsing Encephalopathy with Cerebellar Ataxia (RECA). In our case, a diagnosis of RECA has been established, and despite an alternative, reasonable cause had been already identified. We describe the case of a child with two recurrent episodes, 2 years apart, of hypotonia and ataxia. In both episodes, a laboratory-confirmed influenza virus infection suggested the diagnosis of influenza-associated encephalopathy. After the second episode, a search for genetic mutations was performed, and ATP1A3 mutation associated to RECA was found. After both episodes, the child was discharged after partial improvement of neurological conditions. The diagnosis of encephalopathy in children is often challenging. A genetic predisposition to neurological decompensation should be suspected in case of recurrent episodes, even if an alternative diagnosis has been established. Indeed, febrile infections may only represent the trigger of neurological involvement. In these patients, the knowledge of a genetic predisposing factors may help in the prevention of neurological episodes by the prompt use of anti-pyrectics and preventive measures as appropriate vaccination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pisapia, Capoluongo, Palmiero, Tascini and Rescigno.)

Background: The aim of the present study was to evaluate in HIV-infected patients treated with a direct-acting antiviral agent (DAA)-based regimen the variables associated with sustained virological response (SVR) and the trend in biochemical parameters and clinical events during and after DAA regimen., Methods: We performed a multicentre retrospective cohort study, enrolling all 243 HIV-HCV-coinfected adult patients treated with DAAs between January 2015 and December 2018 in one of the nine participating Infectious Disease Centers in southern Italy, eight in Campania and one in Apulia., Results: Of the 243 patients enrolled, 233 (95.9%) obtained an SVR at 12 weeks (SVR12). Of the 10 patients with non-SVR, 7 were tested for NS3, NS5A and NS5B resistance-associated substitutions (RASs) by sequencing analysis and 6 showed at least 1 major RAS in 1 HCV region (all in NS5A, 2 in NS5B and 1 in NS3). Comparing the 233 patients achieving SVR and the 10 non-achievers, no variable was independently associated with non-SVR. During and after DAA regimen, no modification in the biochemical parameters and clinical events was observed; however, the serum cholesterol and low-density lipoprotein (LDL) levels showed an increase (from 159 ±41.3 mg/dl at baseline to 174 ±44.5 mg/dl at week 12 after stopping treatment, P<0.001, and from 92 ±34.6 mg/dl to 109.4 ±73.7 mg/dl, P=0.002, respectively)., Conclusions: The treatment with DAAs led to a high SVR12 rate in HIV-HCV-coinfected subjects, irrespective of epidemiological, clinical or virological characteristics. However, the DAA regimen was associated with an increase in total- and LDL-cholesterol, to be taken into account in the management of HIV infection.

Aims: This study is aimed at assessing the efficacy of an active search and treat strategy for HBV-infected subjects in an endemic area (Campania, Italy). To do this, we created a cooperation bundle between 24 General Practitioners (GPs) and 3 Hospital Liver Units (HLU). We assessed whether this strategy improved the detection of HBV infection in patients at risk and the overall quality of care, with the aim of reducing liver disease progression., Methods: We estimated that, among about 20,000 patients cared for by the 24 GPs, approximately 280 patients unaware of or underestimating HBV infection would be found. Identified patients were to be referred to the HLU for clinical evaluation and treatment from February 2016 for 12 months., Results: Unexpectedly, screening and enrolment were poor (48 patients only). GP workloads, patient financial difficulties, and patients' refusal were the major causes of enrolment failure according to GPs. All patients referred to HLU completed the program; most of them were HBV inactive carriers., Conclusions: This program failed to scavenge chronic HBV-infected patients in an endemic area and establish a successful clinical collaboration between GPs and HLU. Underlying reasons are diverse and call for new strategies to implement cooperation between primary care providers and hospital specialists.

Background: The patatin-like phospholipase domain-containing 3 gene (PNPLA3) has been associated with liver steatosis and disease progression in nonalcoholic steatohepatitis and chronic hepatitis C., Aims: The aim of the present study was to evaluate the influence of the PNPLA3 I148M polymorphisms on the clinical, histological, viral, and host parameters in Italian patients with chronic hepatitis B (CHB)., Methods: Ninety-nine patients with CHB entered the study and underwent a clinical, histological, virological, and biochemical evaluation. PNPLA3 (p.I148M) variants were genotyped., Results: PNPLA3 rare variant (148M) was significantly associated with liver steatosis (p = 0.0019) and cholesterol (p = 0.04) levels, but not with fibrosis or histological activity index. The 13 patients with severe liver steatosis (score > 3) (38%) were more frequently homozygous for PNPLA3 148M variant than the 86 without (6%, p = 0.003). At logistic regression analysis, severe steatosis was independently associated with the rare allele (p = 0.001) and waist circumference, but not with body mass index (BMI)., Conclusions: In our CHB patients, the PNPLA3 polymorphisms influenced the development of liver steatosis, but not fibrosis status. The association of PNPLA3 p.I148M with liver steatosis increased with the greater amount of abdominal fat, irrespective of BMI.

It is still a matter of debate whether nucleoside/nucleotide analogues should be administered as prophylaxis to hepatitis B surface antigen (HBsAg)-negative/antibodies against hepatitis B core antigen (anti-HBc)-positive patients with immunosuppression or whether these patients should be closely monitored and early treatment administered to those who become HBsAg-positive. We describe a reactivation of occult HBV infection emerging with the case of acute hepatitis B in the wife of an HBsAg-negative/anti-HBc-positive subject treated with rituximab-based chemotherapy for chronic lymphocytic leukaemia.

Background and Aim: To evaluate in anti-HCV-positive patients the clinical impact of the rs35761398 variant of the CNR2 gene leading to the substitution of Gln (Q) of codon 63 of the cannabinoid receptor 2 (CB2) with Arg (R)., Patients and Methods: 253 consecutive anti-HCV-/HCV-RNA-positive patients were enrolled, of whom 53 were HCV carriers with persistently normal ALT (PNALT group) and 200 had a history of steadily abnormal serum ALT values (abnormal ALT group). All patients were naive for antiviral therapy and were screened for the CNR2 rs35761398 polymorphism by a TaqMan assay., Results: Subjects in the PNALT group, compared with those in the abnormal ALT group were older (58.5±12 vs. 50.7±12.4 years, p = 0.001), more frequently female (66% vs. 42%, p = 0.003), with lower body mass index (BMI) (24.5±3.1 vs. 26.6±4.6, p = 0.003), and more frequently with HCV genotype 2 (43.1% vs 17.7%, p = 0.0002) and CB2-63 QQ variant (34% vs. 11%, p = 0.0001). Considering all 253 patients, no difference in the demographic, biochemical, or virological data was observed between patients in the different CB2-63 variants. The logistic regression analysis identified CB2-63 QQ, HCV genotype 2, older age and lower BMI as independent predictors of PNALT (p<0.00001)., Discussion: The CB2-63 QQ variant in HCV patients was independently associated with the PNALT status.

INTRODUCTION. In patients with chronic hepatitis C it is still debated whether previous exposure to the hepatitis B virus, diagnosed from the presence of the anti-HBc antibody, is linked to a greater risk of severe hepatitis. The aim of the study was to evaluate whether the presence of anti-HBc antibodies is associated with cirrhosis in patients with HBsAg-negative chronic hepatitis C. MATERIAL AND METHODS. Two hundred twenty-two consecutive HBsAg-negative patients with HCV-related chronic hepatitis were enrolled at their first liver biopsy. Ishak's scoring system was used to grade necroinflammation and fibrosis and the patients with stage 5 or 6 were considered as having histological cirrhosis. RESULTS. Patients with histological cirrhosis had a higher mean age, AST, ALT, a lower platelet count and prothrombin activity compared to those with milder fibrosis. The presence of anti-HBc was identified in 21 (63.6%) of the 33 patients with fibrosis score 5 or 6 and in 56 (29.6%; p < 0.001) of the 189 with score ≤ 4. Patients with cirrhosis had a significantly higher grading than those without cirrhosis (median = 8, IQR 6-11 vs. Median = 6, IQR = 4-8, respectively, p < 0.001). A multivariate logistic regression analysis showed that age, sex and anti-HBc positivity were independent predictors of histological cirrhosis. CONCLUSION. Our data support the idea that in patients with chronic hepatitis C the presence in serum of anti-HBc is associated with histological cirrhosis and is therefore a marker of clinical value.

The aim of the study was to evaluate clinical and virological differences in HBV reactivation between patients with overt and occult HBV infection. Twenty-three consecutive patients with symptomatic HBV reactivation occurring during or after immunosuppressive therapy were enrolled in a retrospective study: 10 with reactivation of overt HBV infection (overt group) and 13 of occult HBV infection (occult group). Twenty-one patients were treated with nucleot(s)ide analogues after HBV reactivation. Regimens including rituximab or fludarabine were administered more frequently in the occult group (61% vs. 31%, respectively). HBV reactivation was severe frequently in the overt (40%) and occult groups (38.4%). Patients in the overt group showed higher HBV-DNA titers (1.1 × 10(8) ± 1.4 × 10(8) vs. 5.1 × 10(5) ± 6.8 × 10(5) IU; P < 0.005). Seven patients died during HBV reactivation, two in the overt and five in the occult group. Of these seven patients, two remained untreated and five had been treated with Lamivudine; of the 16 patients showing remission of HBV reactivation, four had been treated with Lamivudine, four with Entecavir, two with Telbivudine, and six with Lamivudine plus Adefovir. It is concluded that HBV reactivation is life-threatening in patients with diseases inhibiting the immune response and/or receiving immunosuppressive drugs. Supportive therapy without antiviral drugs or Lamivudine monotherapy may not be effective for treating patients with HBV reactivation., (Copyright © 2011 Wiley-Liss, Inc.)