Background: Hepatitis E virus (HEV) infection poses a significant health risk across diverse demographic groups, particularly among pregnant women, immunocompromised individuals, patients with chronic liver disease, and the elderly. The global epidemiology of HEV reveals distinct patterns of prevalence, transmission, and disease severity among these populations, necessitating targeted vaccination strategies. The licensing of the Hecolin (HEV 239) vaccine offers promise, but gaps in clinical trial data and varying immune responses in high-risk groups challenge its widespread applicability. Scope: This review synthesizes data on HEV’s epidemiology, discusses the susceptibility of vulnerable populations, evaluates the efficacy and safety of HEV 239, and highlights the urgent need for clinical research tailored to these groups. Key findings underscore the complexity of vaccine response influenced by immunological, physiological, and environmental factors. Additionally, potential advancements in vaccine technology, including the development of broad-spectrum vaccines and innovative delivery systems, are discussed as future directions. Strategies: Addressing regulatory, economic, and logistical barriers remains crucial for effective HEV vaccination programs. A multidisciplinary approach integrating public health policy, rigorous clinical evaluations, and collaborative frameworks is essential to ensure equitable access to HEV vaccination, ultimately improving health outcomes on a global scale.

Overexpression of apoptosis-stimulating protein 2 of p53 (ASPP2) induces apoptotic cell death in hepatoma cells (e.g. HepG2 cells) by enhancing the transactivation activity of p53, but long-term ASPP2 overexpression fails to induce more apoptosis since activation of the epidermal growth factor/epidermal growth factor receptor/SOS1 pathway impairs the pro-apoptotic role of ASPP2. In this study, in recombinant adenovirus-ASPP2-infected HepG2 cells, ASPP2 overexpression induces amphiregulin expression in a p53-dependent manner. Although amphiregulin initially contributes to ASPP2-induced apoptosis, it eventually impairs the pro-apoptotic function of ASPP2 by activating the epidermal growth factor/epidermal growth factor receptor/SOS1 pathway, leading to apoptosis resistance. Moreover, blocking soluble amphiregulin with a neutralizing antibody also significantly increased apoptotic cell death of HepG2 cells due to treatment with methyl methanesulfonate, cisplatin, or a recombinant p53 adenovirus, suggesting that the function of amphiregulin involved in inhibiting apoptosis may be a common mechanism by which hepatoma cells escape from stimulus-induced apoptosis. Thus, our data elucidate an apoptosis-evasion mechanism in hepatocellular carcinoma and have potential implications for hepatocellular carcinoma therapy.

SARS-CoV-2 vaccination has been recommended for liver transplant (LT) recipients. However, our understanding of inactivated vaccine stimulation of the immune system in regulating humoral and cellular immunity among LT recipients is inadequate. Forty-six LT recipients who received two-dose inactivated vaccines according to the national vaccination schedule were enrolled. The clinical characteristics, antibody responses, single-cell peripheral immune profiling, and plasma cytokine/chemokine/growth factor levels were recorded. Sixteen (34.78%) LT recipients with positive neutralizing antibody (nAb) were present in the Type 1 group. Fourteen and 16 LT recipients with undetected nAb were present in the Type 2 and Type 3 groups, respectively. Time from transplant and lymphocyte count were different among the three groups. The levels of anti-RBD and anti-S1S2 decreased with decreasing neutralizing inhibition rates. Compared to the Type 2 and Type 3 groups, the Type 1 group had an enhanced innate immune response. The proportions of B, DNT, and CD3+CD19+ cells were increased in the Type 1 group, whereas monocytes and CD4+ T cells were decreased. High CD19, high CD8+CD45RA+ cells, and low effector memory CD4+/naïve CD4+ cells of the T-cell populations were present in the Type 1 group. The Type 1 group had higher concentrations of plasma CXCL10, MIP-1 beta, and TNF-alpha. No severe adverse events were reported in all LT recipients. We identified the immune responses induced by inactivated vaccines among LT recipients and provided insights into the identification of immunotypes associated with the responders.

The understanding of how the host immune response differs in T-cell phenotype and memory formation during SARS-CoV-2 infection in liver transplant recipients (LTRs) remains limited. LTRs who recovered from COVID-19 infection without prior vaccination represent a unique population for studying immune responses to SARS-CoV-2. Six LTRs with positive neutralizing antibodies (nAb+) and six LTRs with negative nAb (nAb-) were included at 6 months following COVID-19 infection. It was found that nAb+ LTRs had higher anti-RBD IgG titers and greater neutralizing percent inhibition compared to nAb- LTRs. Fifteen T-cell subsets were identified in COVID-19 convalescent LTRs, and it was shown that only terminal effector CD8+ - 3 decreased in the nAb+ group, while elevated IL-10 expression levels were found in the nAb- group. After stimulation with the SARS-CoV-2 XBB spike peptide pool in vitro, it was observed that the nAb+ group exhibited an increase in effector memory CD4+ cells with lower PD-1 expression, a reduction in effector memory CD4+ - 2 cells, and terminal effector CD8+ - 3 cells, while the nAb- group showed high expression of CTLA-4 and IL-10 in terminal effector CD8+ - 3 cells. Four SARS-CoV-2-specific T-cell subsets were identified, with high expression of TNF-α and IFN-γ in terminal effector CD8+ - 1 and terminal effector CD8+ - 2 cells in both groups. Perforin was mainly detected in terminal effector CD8+ - 2 cells in nAb+ LTRs. In addition to these proportional differences, stem cell memory CD4+ cells with higher IL-17A expression and stem cell memory CD8+ cells with higher CTLA-4 expression were also found in nAb- LTRs. These findings suggest that LTRs who developed nAb+ following SARS-CoV-2 infection exhibit stronger T-cell responses, with more robust immune activation and memory recall, compared to nAb- LTRs. This study underscores the importance of understanding T-cell responses during SARS-CoV-2 recovery for guiding vaccination strategies and managing immunity in LTRs.

Chronic systemic stress (CSS) is associated with the progression of hepatocellular carcinoma (HCC), yet the molecular mechanisms linking physiological exha

Primary sclerosing cholangitis (PSC) is an immune-mediated cholestatic liver disease. Its molecular etiology remains poorly defined, hindering the development of mechanism-based diagnostics and therapies. Therefore, this study aimed to identify key molecular drivers and causal biomarkers of PSC by integrating transcriptomics, machine learning, and genetic causal inference.