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Purpose: There is limited research on whether Proton Pump Inhibitors (PPIs) will affect the efficacy of immune checkpoint inhibitors (ICIs) in treating hepatocellular carcinoma (HCC).This study aimed to determine whether PPIs affect the survival outcomes of patients with HBV-associated advanced HCC receiving combination therapy based on ICIs. Methods: We retrospectively analyzed patients with hepatitis B virus (HBV)-associated advanced HCC who underwent ICIs combination therapy from January 1, 2020, to December 30, 2022. Patients were stratified into PPI and non-PPI groups based on whether they received PPI treatment within 30 days before or after ICIs therapy. Patients' survival and the risk of PPI-associated mortality was assessed. Adverse events were also evaluated. Results: A total of 183 patients with HBV-associated HCC treated with ICI combination therapy were included. The median survival time (12.5 months vs 13.7 months, P = 0.285) and incidence of adverse events (P = 0.729) did not significantly differ between the PPI and non-PPI groups. Even after propensity score matching, the difference in median overall survival (OS) between the two groups was not significant (10.7 months vs 11.4 months; P = 0.596) and the patient's OS is not significantly related to the dosage of PPI application (P > 0.05).However, according to our subgroup analysis, among HCC patients with a serum HBV DNA concentration ≥ 200 IU/mL, the use of PPIs significantly increased the risk of mortality in patients receiving ICI combination therapy (P = 0.024). Conclusion: PPIs do not notably influence the survival prognosis of patients receiving ICI combination therapy for HBV-associated advanced HCC. However, among patients with high levels of HBV DNA, PPIs increase the risk of mortality. Therefore, antiviral therapy should be intensified in the patients with HBVDNA > 200 IU/mL. Additionally, PPIs do not impact the incidence of adverse reactions in these patients. [ABSTRACT FROM AUTHOR]

The ongoing outbreak of 2019 novel coronavirus disease (COVID-19) originating from Wuhan, China, has spread rapidly across the world (1). Both human-to-human and asymptomatic transmission have been reported (2,3). Phylogenetic [...]

ABSTRACT Clinical studies of tenofovir amibufenamide (TMF) and tenofovir alafenamide (TAF) treatment in patients with HBV‐related decompensated cirrhosis (HBV‐DC) are limited. This study evaluated the efficacy and safety of TMF versus TAF in naive‐treated patients with first‐time HBV‐DC. Based on the antiviral drug used, patients were categorised into the TMF group and the TAF group. Virological and serological responses, hepatic and renal functions and blood lipid changes in both groups were evaluated during 48 weeks of treatment. A total of 98 patients were enrolled, 45 in the TMF group and 53 in the TAF group. At 48 weeks of treatment, the proportions of patients who achieved complete virological response (CVR) were 85.7% and 90.7%, respectively (p = 0.791). Improvement of at least 2 points in Child–Turcotte–Pugh scores was observed in 64.3% versus 79.1% (p = 0.169) of the patients. There were no significant changes in serum creatinine, estimated glomerular filtration rate or total cholesterol from baseline to week 48 between the two groups. Cystatin C remained stable in the TMF group but increased over time in the TAF group (p < 0.001). Low‐density lipoprotein cholesterol remained stable in the TMF group but increased significantly in the TAF group at week 48 (p = 0.015). These results suggest that both TMF and TAF can rapidly suppress HBV replication, improve hepatic function and have no negative effects on renal function among patients with HBV‐DC. Regarding lipid metabolism, both showed a better safety, while regular monitoring of blood lipid levels is recommended. [ABSTRACT FROM AUTHOR]

Classically, all hepatitis E virus (HEV) variants causing human infection belong to the genus Paslahepevirus (HEV-A). However, the increasing cases of rat HEV infection in humans since 2018 challenged this dogma, posing increasing health threats. Herein, we investigated the underlying mechanisms dictating the zoonotic potentials of different HEV species and their possible cross-protection relationships. We found that rat HEV virus-like particles (HEV VLPs ) bound to human liver and intestinal cells/tissues with high efficiency. Moreover, rat HEV VLPs and infectious rat HEV particles penetrated the cell membrane and entered human target cells postbinding. In contrast, ferret HEV VLPs showed marginal cell binding and entry ability, bat HEV VLPs and avian HEV VLPs exhibited no binding and entry potency. Structure-based three-dimensional mapping identified that the surface spike domain of rat HEV is crucial for cell binding. Antigenic cartography indicated that rat HEV exhibited partial cross-reaction with HEV-A. Intriguingly, sera of HEV-A infected patients or human HEV vaccine Hecolin® immunized individuals provided partial cross-protection against the binding of rat HEV VLPs to human target cells. In summary, the interactions between the viral capsid and cellular receptor(s) regulate the distinct zoonotic potentials of different HEV species. The systematic characterization of antigenic cartography and serological cross-reactivity of different HEV species provide valuable insights for the development of species-specific diagnosis and protective vaccines against zoonotic HEV infection., Competing Interests: Competing interests statement:J.S. and S.S. report provisional patent applications for “Hepatitis E virus-like particles and uses thereof” covering the utilization of virus-like particles for serodiagnosis and vaccines (US PTO application no. 63/166,698 and PCT application no. PCT/CN2022/081996). The other authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

Objective: To detect T cell immunoglobulin and mucin domain-containing molecule 3(Tim-3) expression on peripheral blood monocyts (PBMs) and explore its effect on inflammatory cytokines production of PBMs in patients with chronic hepatitis B (CHB)., Methods: The expression of Tim-3 protein and mRNA on PBM subsets was respectively determined using flow cytometry and real-time quantitative RT-PCR (qRT-PCR) in CHB patients at different phases. After PBMs were stimulated with both recombinant human galectin-9 and lipopolysaccharide (LPS) in active CHB patients, the supernatants were collected to measure the levels of proinflammatory factors including TNF-α, IL-1β and IL-6 by ELISA., Results: Compared with healthy controls and CHB patients at immune active (IA) phase, the expression of Tim-3 was significantly up-regulated in PBMs of CHB patients at immune tolerance (IT) phase (P<0.01). The level of Tim-3 expression on both CD14(+);CD16-; and CD14(+);CD16(+); monocyte subsets of CHB patients at IT phase was significantly higher than that of the CHB patients at IA phase and of healthy controls (P<0.05). qRT-PCR further demonstrated that the level of Tim-3 mRNA on monocytes of CHB patients at IA phase was also higher than that of healthy controls (P=0.040). There was a positive correlation between the expression of Tim-3 on CD14(+); monocytes and serum ALT level in IA CHB patients (r=0.362, P=0.028). The levels of proinflammatory factors in supernatants, such as TNF-α, IL-1β and IL-6 increased significantly in monocytes stimulated by LPS and galectin-9, compared with ones by LPS alone., Conclusion: Tim-3 expression, which is up-regulated on PBMs of CHB patients, is negatively correlated to the level of ALT in sera of IA CHB patients, and Tim-3/galectin-9 pathway might promote proinflammatory factors production of monocytes stimulated with LPS.