Circulating HBsAg-specific B cells are partially rescued in chronically HBV-infected patients with functional cure.

It is well established that humoral immunity targeting hepatitis B virus surface antigen (HBsAg) plays a critical role in viral clearance and clinical cure. However, the functional changes in HBsAg-specific B cells before and after achieving functional cure remain poorly understood. In this study, we characterized circulating HBsAg-specific B cells and identified functional shifts and B-cell epitopes directly associated with HBsAg loss.

Noncanonical regulation of HOIL-1 on cancer stemness and sorafenib resistance identifies pixantrone as a novel therapeutic agent for HCC.

Background And Aims: Cancer stem cells (CSCs) contribute to therapy resistance in HCC. Linear ubiquitin chain assembly complex (LUBAC) has been reported to accelerate the progression of cancers, yet its role in the sorafenib response of HCC is poorly defined. Herein, we investigated the impact of LUBAC on sorafenib resistance and the CSC properties of HCC, and explored the potential targeted drugs.

HBV Core-specific CD4 T cells correlate with sustained viral control upon off-treatment in HBeAg-positive chronic hepatitis B patients.

Background & Aims: Treatment with nucleos(t)ide analogue (NA) efficiently suppresses viral replication in patients with chronic HBV infection, yet HBV relapses frequently upon NA withdrawal; the detailed immunomodulatory compounds for sustained viral control of HBV upon NA interruption have yet to be fully clarified. This study aimed to elucidate the role of T cells specific for distinct HBV peptides in sustained response upon discontinuation of antiviral treatment.

Methods: A total of 48 patients with HBeAg-positive chronic hepatitis B receiving NA treatment and withdrawal were included longitudinally in a retrospective and prospective cohort.

Differential response of HBV envelope-specific CD4 + T cells is related to HBsAg loss after stopping nucleos(t)ide analogue therapy.

Background And Aim: Long-term maintenance of viral control, even HBsAg loss, remains a challenge for chronic hepatitis B (CHB) patients undergoing nucleos(t)ide analogue (NA) discontinuation. This study aimed to investigate the relationship between HBV-specific T-cell responses targeting peptides spanning the whole proteome and clinical outcomes in CHB patients after NA discontinuation.

Approach And Results: Eighty-eight CHB patients undergoing NA discontinuation were classified as responders (remained relapse-free up to 96 weeks) or relapsers (relapsed patients who underwent NA retreatment for up to 48 weeks and reachieved stable viral control).

CTLA4CD4CXCR5FOXP3 T cells associate with unfavorable outcome in patients with chronic HBV infection.

Background: A major barrier to achieving a favorable outcome of chronic HBV infection is a dysregulated HBV-specific immune response resulting from immunosuppressive features of FOXP3 T cells. A better definition of FOXP3 T cells is essential for improving the prognosis of HBV infection. We aimed to investigate the role of CD4CXCR5FOXP3 T cells with CTLA4 expression in patients with chronic HBV infection.

Interferon α facilitates anti-HBV cellular immune response in a B cell-dependent manner.

Objectives: Dissecting the underlying mechanism of T cells remodeling mediated by interferon α (IFN-α) is indispensable for achieving an optimum therapeutic response in chronic hepatitis B (CHB) patients. However, little is known about B cells in this process. This study aims to elucidate the roles of B cells in IFN-α-mediated anti-hepatitis B virus (HBV) cellular immunity.

Identification and Mapping of HBsAg Loss-Related B-Cell Linear Epitopes in Chronic HBV Patients by Peptide Array.

Identification of immunogenic targets against hepatitis B virus (HBV)-encoded proteins will provide crucial advances in developing potential antibody therapies. In this study, 63 treatment-naïve patients with chronic HBV infection and 46 patients who achieved hepatitis B surface antigen loss (sAg loss) following antiviral treatment were recruited. Moreover, six patients who transitioned from the hepatitis B e antigen-positive chronic infection phase (eAgCInf) to the hepatitis phase (eAgCHep) were enrolled from real-life clinical practice.

Hepatocyte-Derived L-Carnitine Restricts Hepatitis B Surface Antigen Loss Through an Immunosuppressive Effect on Germinal Center-Related Immune Cells.

Background: The outcome of hepatitis B virus (HBV) infection is significantly affected by host immune response; herein, we aim to dissect the effect of L-carnitine (L-Cn) on germinal center (GC)-related immune cells and the influence on the prognosis of HBV infection.

Methods: In vitro and in vivo experiments were performed in patients with chronic HBV infection and a hydrodynamic injection mouse model.

Results: In vitro assays revealed that L-Cn significantly reduced GC-related immune responses and enhanced immunosuppressive profiles.

Expanded circulating follicular dendritic cells facilitate immune responses in chronic HBV infection.

Background: The restoration of host hepatitis B virus (HBV)-specific antiviral immunity is an effective strategy for hepatitis B recovery. Follicular dendritic cells (FDCs) play a crucial role in immune regulation. The goal of the present study was to investigate the characteristics and functions of FDCs in chronic HBV infection.

Identification of the association between HBcAg-specific T cell and viral control in chronic HBV infection using a cultured ELISPOT assay.

Hepatitis B virus (HBV)-specific T cells play a critical role in determining the outcome of HBV infection. However, T cell response induced by predominant Ag in chronic infection is hardly detectable owing to the lack of a suitable assay. We herein established an optimized method to enumerate HBV-specific T cells and assessed the association between HBV surface Ag (HBsAg) and HBV DNA.

IL-21 receptor signaling is essential for control of hepatocellular carcinoma growth and immunological memory for tumor challenge.

Hepatocellular carcinoma (HCC) is a typical inflammation-associated cancer. IL-21 regulates both innate and adaptive immune responses and has key roles in antitumor and antiviral responses. However, the role of IL-21 in HCC development is poorly defined.