Background Chemokine (C–C motif) ligand 19 (CCL19) is a leukocyte chemoattractant that plays a crucial role in cell trafficking and leukocyte activation. Dysfunctional CD8+ T cells play a crucial role in persistent HBV infection. However, whether HBV can be cleared by CCL19-activated immunity remains unclear. Methods We assessed the effects of CCL19 on the activation of PBMCs in patients with HBV infection. We also examined how CCL19 influences HBV clearance and modulates HBV-responsive T cells in a mouse model of chronic hepatitis B (CHB). In addition, C–C chemokine-receptor type 7 (CCR7) knockdown mice were used to elucidate the underlying mechanism of CCL19/CCR7 axis-induced immune activation. Results From in vitro experiments, we found that CCL19 enhanced the frequencies of Ag-responsive IFN-γ+ CD8+ T cells from patients by approximately twofold, while CCR7 knockdown (LV-shCCR7) and LY294002 partially suppressed IFN-γ secretion. In mice, CCL19 overexpression led to rapid clearance of intrahepatic HBV likely through increased intrahepatic CD8+ T-cell proportion, decreased frequency of PD-1+ CD8+ T cells in blood and compromised suppression of hepatic APCs, with lymphocytes producing a significantly high level of Ag-responsive TNF-α and IFN-γ from CD8+ T cells. In both CCL19 over expressing and CCR7 knockdown (AAV-shCCR7) CHB mice, the frequency of CD8+ T-cell activation-induced cell death (AICD) increased, and a high level of Ag-responsive TNF-α and low levels of CD8+ regulatory T (Treg) cells were observed. Conclusions Findings in this study provide insights into how CCL19/CCR7 axis modulates the host immune system, which may promote the development of immunotherapeutic strategies for HBV treatment by overcoming T-cell tolerance.

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Numerous canonical cellular signaling pathways modulate hepatitis B virus (HBV) replication. HBV genome products are known to play a significant role in regulating these cellular pathways for the liver’s viral-related pathology and physiology and have been identified as the main factor in hepatocarcinogenesis. Signaling changes during viral replication ultimately affect cellular persistence, multiplication, migration, genome instability, and genome damage, leading to proliferation, evasion of apoptosis, block of differentiation, and immortality. Recent studies have documented that numerous signaling pathway agonists or inhibitors play an important role in reducing HBV replication in vitro and in vivo, and some have been used in phase I or phase II clinical trials. These optional agents as molecular therapeutics target cellular pathways that could limit the replication and transcription of HBV or inhibit the secretion of the small surface antigen of HBV in a signaling-independent manner. As principle-based available information, a combined strategy including antiviral therapy and immunomodulation will be needed to control HBV infection effectively. In this review, we summarize recent findings on interventions of molecular regulators in viral replication and the interactions of HBV proteins with the components of the various targeting cellular pathways, which may assist in designing novel agents to modulate signaling pathways to prevent HBV replication or carcinogenesis.

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Background The prognosis of patients with liver failure (LF) depends significantly on the etiologies and clinical indicators. Methods The retrospective cohort study included 637 LF patients between 2018 and 2020, including the subclasses of acute liver failure (ALF), subacute liver failure (SLF), acute-on-chronic liver failure (ACLF), subacute-on-chronic liver failure (SALF), and chronic liver failure (CLF). Multivariate logistic regression analysis was used to screen clinical indicators of death patients. We analyzed the receiver operating characteristic curves (ROCs) and cut-off values to assess prognosis criteria. Results HBV infection was present in 64.52% of LF patients. SALF (41.36%) is the main subclass of the hepatitis B virus-related LF (HBV-LF) group, while chronic liver failure (32.30%) is the main subclass of the non-HBV-related LF group in southeast China. Between 2018 and 2020, the incidence of HBV-LF decreased significantly, ranging from 72.36–59.74%, and the spontaneous survival rates of HBV-LF patients were substantially lower than those of the non-HBV-LF group (36.43 ~ 44.93% vs. 58.97 ~ 63.64%). Infection and cirrhosis were the primary causes of both groups. The age and total bilirubin value of the HBV-LF dead patients were significantly higher, and the number of days of hospitalization was significantly shorter than those of the survivors. The ages of the dead patients of the non-HBV-LF group were significantly higher than those of the survivors. The prothrombin time-international normalized ratio (PT-INR) of 2.05, 1.92, or 2.11, and antithrombin III (AT III) of 24.50%, which were proposed as prognostic criteria for the HBV-SALF, non-HBV-subacute liver failure, non-HBV-acute-on-chronic liver failure, and HBV-acute liver failure subclasses, respectively. Conclusions The incidence of HBV-LF is decreasing yearly. AT III, as a new prognostic criterion, has an excellent discriminative ability on the outcomes of the HBV-ALF subclass.

The use of replication-competent hepatitis B virus (HBV) DNA to construct a mouse model will help explore antiviral treatment strategies for more than 240 million patients infected with HBV worldwide. Eradication of chronic HBV infection can effectively block the adverse consequences of HBV-induced hepatic cirrhosis, failure and carcinoma. The core reason that HBV is difficult to eradicate is that most of infected people develop chronic HBV infection due to the establishment of immune tolerance. Here, we introduce a mouse model of adeno-associated virus (AAV)-HBV transfection, which produces HBV surface antigen (HBsAg) that can be maintained for more than 6 months. During virus replication, intermediates, transcripts, and proteins can be detected in peripheral blood. At the same time, the prerequisite for studying liver disease formation and immunotherapy through in vitro experiments is to isolate hepatic subgroup cells. Here, we describe a cell sorting method based on liberase perfusion technology combined with low-speed centrifugation and magnetic bead antibody labeling to purify hepatic parenchymal cells (PCs) and non-parenchymal cells (NPCs) step by step from murine liver, such as hepatic sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs), which will help accelerate the study of the genetic and clearance mechanistic of chronic HBV infection.

In the published article, there was an error in the affiliations. Instead of three, there are only two affiliations. The original affiliation 2 was removed. The correct affiliations are listed below:Instead of