Immune drivers of HBsAg loss in HBeAg-negative CHB patients after stopping nucleotide analog and administration of Peg-IFN

Islam, Mojahidul; Kumar, Karan; Sevak, Jayesh Kumar; Jindal, Ankur; Vyas, Ashish Kumar; Ramakrishna, Gayatri; Kottilil, Shyamasundaran; Sharma, Manoj Kumar; Sarin, Shiv Kumar; Trehanpati, Nirupama

doi:10.1097/hc9.0000000000000098

Cited by 4 publications

(1 citation statement)

References 35 publications

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“…HBsAg loss and HBsAg seroconversion to anti- HBs may improve liver histopathology, increase survival rates, and reduce liver disease complications such as hepatocellular carcinoma ( Ge et al 2015 ; Tseng et al 2020 ; Tseng et al 2022 ). Nucleotide analogues (NAs) and interferon alpha (IFN-α) are first-line agents for the treatment of CHB ( Islam et al 2023 ). NAs, which act as reverse transcriptase inhibitors, can effectively suppress the viral load of HBV.…”

Section: Introductionmentioning

confidence: 99%

Guanylate-Binding Protein 1 (GBP1) Enhances IFN-α Mediated Antiviral Activity against Hepatitis B Virus Infection

Li,

Luo,

et al. 2024

Polish Journal of Microbiology

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Interferon-alpha (IFN-α) is a first-line drug for treating chronic hepatitis B (CHB). Guanylate-binding protein 1 (GBP1) is one of the interferon-stimulating factors, which participates in the innate immunity of the host and plays an antiviral and antibacterial role. In this study, we explored how GBP1 is involved in IFN-α antiviral activity against HBV. Before being gathered, HepG2-NTCP and HepG2 2.15 cells were transfected with the wild-type hGBP1 plasmid or si-GBP1, respectively, and followed by stimulation with Peg-IFNα-2b. We systematically explored the role of GBP1 in regulating HBV infection in cell models. Additionally, we also examined GBP1 levels in CHB patients. GBP1 activity increased, and its half-life was prolonged after HBV infection. Overexpression of GBP1 inhibited the production of HBsAg and HBeAg, as well as HBs protein and HBV total RNA levels, whereas silencing of GBP1 inhibited its ability to block viral infections. Interestingly, overexpressing GBP1 co-treatment with Peg-IFNα-2b further increased the antiviral effect of IFN-α, while GBP1 silencing co-treatment with Peg-IFNα-2b partly restored its inhibitory effect on HBV. Mechanistically, GBP1 mediates the anti-HBV response of Peg-IFNα-2b by targeting HBs. Analysis of clinical samples revealed that GBP1 was elevated in CHB patients and increased with Peg-IFNα-2b treatment, while GBP1 showed good stability in the interferon response group. Our study demonstrates that GBP1 inhibits HBV replication and promotes HBsAg clearance. It is possible to achieve antiviral effects through the regulation of IFN-α induced immune responses in response to HBV.

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Section: Introductionmentioning

confidence: 99%

Guanylate-Binding Protein 1 (GBP1) Enhances IFN-α Mediated Antiviral Activity against Hepatitis B Virus Infection

Li,

Luo,

et al. 2024

Polish Journal of Microbiology

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Investigating the role of GTPase in inhibiting HBV replication and enhancing interferon therapy efficacy in chronic hepatitis B patients

Quan,

Wang,

et al. 2024

Microbial Pathogenesis

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Peg-IFNα combined with hepatitis B vaccination contributes to HBsAg seroconversion and improved immune function

Liu,

Ren,

et al. 2024

Virol J

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Purpose The purpose of this study was to investigate immunological variations between a group that received the hepatitis B vaccine and a non-vaccine group. We focused on a cohort that achieved HBsAg seroclearance after Peg-IFNα treatment of CHB. Methods We enrolled twenty-eight individuals who achieved HBsAg seroclearance after Peg-IFNα treatment. They were divided into two groups: a vaccine group (n = 14) and a non-vaccine group (n = 14). We assessed lymphocyte subpopulations, B cell- and T cell-surface costimulatory/inhibitory factors, cytokines and immunoglobulin levels were detected at different time points to explore immune-function differences between both groups. Results The seroconversion rate in the vaccine group at 24 weeks post-vaccination was 100%, which was significantly higher (p = 0.006) than that of the non-vaccine group (50%). Additionally, more individuals in the vaccine group exhibited anti-HBs levels exceeding 100 IUs/L and 300 IUs/L compared to the non-vaccine group (p < 0.05). The vaccine group demonstrated significantly increase total B cells and class-switched B cells at 24 weeks and plasma cells, CD80+B cells, Tfh cells, and ICOS+Tfh cell at 12 weeks, compared with baseline levels (p < 0.05). Conversely, Bregs (CD24+CD27+ and CD24+CD38high) decreased significantly at 24 weeks (p < 0.05). None of the above changes were statistically significance in the non-vaccine group (p > 0.05). Total IgG increased significantly in the vaccine group, and IL-2, IL-5, and IL-6 concentrations increased significantly at week 24 (p < 0.05). Differences in various types of cytokines and immunoglobulins in the plasma of the non-vaccine group were not significant (p > 0.05). Anti-HBs titers positively correlated with Th1/Th2 cells at 24 weeks (r = 0.448 and 0.458, respectively, p = 0.022 and 0.019, respectively), and negatively with CD24+CD38highBreg cells (r = -0.402, p = 0.042). Conclusions After achieving HBsAg seroclearance through Peg-IFNα treatment for CHB, administering the hepatitis B vaccine significantly increased anti-HBs-seroconversion rates and antibody levels. We also observed significant immunological differences between the vaccine and non-vaccine groups. Specifically, the vaccine group exhibited significant increases in B cells, plasma cells, and Tfh cells, while Breg levels was significantly lower. These immunological changes are likely conducive to the production of anti-HBs antibodies. However, in the non-vaccine group, the observed changes were not significantlly significant.

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Immune drivers of HBsAg loss in HBeAg-negative CHB patients after stopping nucleotide analog and administration of Peg-IFN

Cited by 4 publications

References 35 publications

Guanylate-Binding Protein 1 (GBP1) Enhances IFN-α Mediated Antiviral Activity against Hepatitis B Virus Infection

Guanylate-Binding Protein 1 (GBP1) Enhances IFN-α Mediated Antiviral Activity against Hepatitis B Virus Infection

Investigating the role of GTPase in inhibiting HBV replication and enhancing interferon therapy efficacy in chronic hepatitis B patients

Peg-IFNα combined with hepatitis B vaccination contributes to HBsAg seroconversion and improved immune function

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