Cellular immune responses are crucial in determining outcomes of the hepatitis B virus (HBV) infection. Ineffective immune responses enable persistent HBV infection and contribute to progressive liver disease. Understanding the mechanisms underlying immunological HBV tolerance and restoring functional adaptive immune responses is essential for successful chronic hepatitis B (CHB) treatment. This study examined the dysregulated immune responses and immunopathological cell states associated with CHB using single-cell RNA sequencing of peripheral blood mononuclear cells to investigate immune cell composition and transcriptional differences between patients with CHB and healthy donors. Phenotypic alterations in the lymphoid and myeloid compartments were observed following HBV infection. T cell immune profiling in patients with CHB showed enrichment of exhausted CD8+ T cells, impaired cytotoxicity of effector CD8+ T cells, and increased regulatory T cell (Treg) suppressive activity. Immature neutrophils and a unique CD14+ monocyte subset (myeloid-derived suppressor cells) exhibited potent immunosuppressive abilities. A novel population of CD14+CD163+VSIG4+ M2-like macrophages with immunosuppressive and anti-inflammatory phenotypes was enriched in a patient with severe CHB and liver failure, indicating a potential contribution to dysfunctional immune responses. Our study demonstrated immune exhaustion and evasion in chronic HBV infection, elucidating its immunopathological features and suggesting new therapeutic strategies for immune-mediated disorders and unresolved chronic HBV infection.

This study investigates the relationship between Cyclin D1 (CCND1) gene and promoter methylation and liver fibrosis (LF)/liver cirrhosis (LC)induced by chronic hepatitis B (CHB). Peripheral blood mononuclear cells (PBMCs) are collected from patients diagnosed with chronic hepatitis B (CHB) and hepatitis B-related LF/LC, as well as from healthy individuals. The mRNA levels and promoter methylation of the CCND1 gene are measured. Single-cell analysis is performed to determine the cell types primarily expressing the CCND1 gene in LF/LC. The GSE84044 dataset is utilized to validate the experimental results. Single-gene GSEA and immune infiltration analyses are conducted to identify significant pathways and immune characteristics associated with the CCND1 gene. The mRNA level of CCND1 in PBMCs from patients with hepatitis B-related LF/LC is elevated compared to those with chronic hepatitis B (CHB) and healthy individuals, while the promoter methylation level of CCND1 is reduced. Single-cell analysis indicates high expression of CCND1 in M2 macrophages (M2) and T cells. The GSE84044 dataset confirms higher CCND1 mRNA levels in liver tissues from patients with CHB-related LF/LC compared to CHB patients. Single-gene GSEA analysis associates CCND1 expression with natural killer cell-mediated cytotoxicity, T cell receptor signaling, and B cell receptor signaling pathways. Increased expression of CCND1 enhances immune infiltration during the fibrosis/cirrhosis process of CHB. The CCND1 expression and promoter methylation may be involved in the process of LF/LC in CHB and may be related to the immune response in the course of the disease.

This study aims to evaluate the diagnostic value of standardized semiquantitative scoring of color Doppler ultrasound combined with liver stiffness measurement (LSM) of sound touch elastography (STE) in chronic hepatitis B (CHB) patients, providing a reference for the liver fibrosis diagnosis.

We performed ultrasound and STE on CHB patients, with liver biopsies as the benchmark. We compared the differences in ultrasound standardized semiquantitative scoring and LSM among patients with different stages of liver fibrosis, and evaluated the diagnostic efficacy of significant liver fibrosis using receiver operating characteristic (ROC) curves and the area under the ROC curve alone or in combination.

The total scores of ultrasound semiquantitative scoring and LSM showed statistically significant differences among patients with different stages of liver fibrosis (P < 0.05). There was no statistically significant difference in the total scores of S0 and S1 stages or in the LSM values (P > 0.05). However, the total scores and LSM values for patients at stages S2 and S3 were both higher than those at stage S0, and increased with the severity of fibrosis staging, with statistically significant differences (P < 0.05). The results of the ROC curve analysis showed that the combined diagnosis of significant liver fibrosis with ultrasound standardized semiquantitative scoring and STE had an area under the curve of 0.807, which was significantly greater than using ultrasound standardized semiquantitative scoring (0.694, P < 0.05) or shear wave elastography alone (0.706, P < 0.05).

Color Doppler ultrasound with standardized semiquantitative scoring combined with STE examination can detect significant liver fibrosis (≥S2) in CHB patients.

Hepatitis B virus (HBV) affects hundreds of millions globally, with many cases stemming from perinatal transmission. Chronic hepatitis B (CHB) in children can progress to cirrhosis and hepatocellular carcinoma (HCC) in adulthood. Treatment options include interferons and nucleos(t)ide reverse transcriptase inhibitors (N[t]RTIs) such as tenofovir alafenamide (TAF).

This review covers the epidemiology of pediatric CHB and current treatments, with a focus on tenofovir-based therapies, particularly tenofovir disoproxil fumarate (TDF) and TAF. TDF has been used for years, but its risks of bone mineral density loss and renal impairment have raised concerns. TAF, with lower systemic exposure, appears to mitigate these risks. Ongoing trials are evaluating TAF's safety in younger children. There are knowledge gaps in long-term safety and the potential for combination therapies.

TAF offers a safer alternative to TDF for children with CHB, showing high antiviral efficacy and fewer side effects. However, more data are needed on its use in younger children and long-term safety. The future of CHB treatment in pediatrics may include combination therapies and personalized approaches, potentially improving outcomes and minimizing risks over a lifetime of treatment. As research progresses, TAF is likely to become a cornerstone in pediatric CHB management.

In patients who progress from acute hepatitis B virus (HBV) infection to a chronic HBV (CHB) infection, CD8+ T cells fail to eliminate the virus and become impaired. A functional cure of CHB likely requires CD8+ T cell responses different from those induced by the infection. Here we report preclinical immunogenicity and efficacy of an HBV therapeutic vaccine that includes herpes simplex virus (HSV) glycoprotein D (gD), a checkpoint modifier of early T cell activation, that augments CD8+ T cell responses. The vaccine is based on a chimpanzee adenovirus serotype 6 (AdC6) vector, called AdC6-gDHBV2, which targets conserved and highly immunogenic regions of the viral polymerase and core antigens fused to HSV gD. The vaccine was tested with and without gD in mice for immunogenicity, and in an AAV8-1.3HBV vector model of antiviral efficacy. The vaccine encoding the HBV antigens within gD stimulates potent and broad CD8+ T cell responses. In a surrogate model of HBV infection, a single intramuscular injection achieved pronounced and sustained declines of circulating HBV DNA copies and HBV surface antigen; both inversely correlated with HBV-specific CD8+ T cell frequencies in spleen and liver.

Hepatitis B virus (HBV) infection remains a significant global health challenge, leading to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Covalently closed circular DNA (cccDNA) and integrated HBV DNA are pivotal in maintaining viral persistence. Recent advances in CRISPR/Cas technology offer innovative strategies to inhibit HBV by directly targeting both cccDNA and integrated HBV DNA or indirectly by degrading HBV RNAs or targeting host proteins. This review provides a comprehensive overview of the latest advancements in using CRISPR/Cas to inhibit HBV, with a special highlight on newer non-double-strand (non-DSB) break approaches. Beyond the canonical use of CRISPR/Cas for target inhibition, we discuss additional applications, including HBV diagnosis and developing models to understand cccDNA biology, highlighting the diverse use of this technology in the HBV field.

Peripheral helper T cells (Tph) are a specialized subset of CD4+ T cells with the ability to help B cells and induce antibody production. Although usually located in ectopic lymphoid-like structures (ELS), inside the peripheral blood, Tph cells can also be identified. The aberrant proliferation and functions of Tph cells are commonly found in the patients with disease. In this review, first we will summarize the biological characteristics of Tph cells, such as the expression of surface molecules, transcription factors and cytokines, and discuss its B cell help functions. Tph cells also have roles in a wide range of human diseases, including autoimmune diseases, infectious diseases, malignancies etc. Therefore, there is a strong interest in targeting Tph cells to improve treat strategies of human diseases.

Chronic hepatitis B (CHB) is caused by HBV infection and affects the lives of millions of people worldwide by causing liver inflammation, cirrhosis, and liver cancer. Interferon-alpha (IFN-α) therapy is a conventional immunotherapy that has been widely used in CHB treatment and achieved promising therapeutic outcomes by activating viral sensors and interferon-stimulated genes (ISGs) suppressed by HBV. However, the longitudinal landscape of immune cells of CHB patients and the effect of IFN-α on the immune system are not fully understood.

Here, we applied single-cell RNA sequencing (scRNA-seq) to delineate the transcriptomic landscape of peripheral immune cells in CHB patients before and after PegIFN-α therapy. Notably, we identified three CHB-specific cell subsets, pro-inflammatory (Pro-infla) CD14+ monocytes, Pro-infla CD16+ monocytes and IFNG+ CX3CR1- NK cells, which highly expressed proinflammatory genes and positively correlated with HBsAg. Furthermore, PegIFN-α treatment attenuated percentages of hyperactivated monocytes, increased ratios of long-lived naive/memory T cells and enhanced effector T cell cytotoxicity. Finally, PegIFN-α treatment switched the transcriptional profiles of entire immune cells from TNF-driven to IFN-α-driven pattern and enhanced innate antiviral response, including virus sensing and antigen presentation.

Collectively, our study expands the understanding of the pathological characteristics of CHB and the immunoregulatory roles of PegIFN-α, which provides a new powerful reference for the clinical diagnosis and treatment of CHB.

There is a pressing need to develop novel drugs for treating patients with chronic hepatitis B (CHB), as commercially available antiviral drugs are endowed with safety and efficacy concerns.

A phase III clinical trial was conducted with a therapeutic vaccine containing two antigens of the hepatitis B virus (HBV; named NASVAC) in 78 patients with CHB expressing both HBV DNA and elevated levels of alanine aminotransferase (ALT) in the blood. Five years after the end of treatment (EOT), 60 NASVAC-recipient patients were enrolled in this long-term follow-up study to evaluate the safety, antiviral potential, and liver-protective capacity of NASVAC.

NASVAC exhibited an excellent safety profile 5 years after EOT. The levels of HBV DNA in the sera were reduced in 55 of the 60 patients, and 45 of them were negative for HBV DNA in the sera. ALT levels were also normalized in 40 of the 60 patients 5 years after EOT. None of the patients receiving NASVAC developed liver cirrhosis or cancer.

The present study is the first to exhibit long-term follow-up data of a finite immune therapy for CHB that is safe and endowed with potent antiviral and liver-protecting capacities.

Viral hepatitis has long been underrated as a danger to global health. The UN only recently called for worldwide action to tackle viral hepatitis and lessen the disease burden in its "2030 Agenda for Sustainable Development". Hepatitis B virus (HBV), which causes liver cirrhosis and malignancy, is a main cause of death globally. This review analyses innovative HBV therapeutic vaccine candidates for which a patent was filed between January 2010 and March 2022 and presents future improvement techniques for vaccine efficacy. Although there is a preventative vaccine for HBV infection, over 3% of people worldwide have the disease on a long-term basis and can no longer benefit from it. Most people will have chronic HBV infection for the rest of their lives once it has been diagnosed. Moreover, only a small percentage of treated patients experience a functional cure with persistent hepatitis B surface antigen reduction. A significant proportion of deaths are caused by liver cirrhosis and hepatocellular cancer, which are both caused by chronic hepatitis B infection. Hence, there is an urgent need for novel medications due to the inadequacies of the current therapies.