Hepatitis B surface antigen clearance in inactive hepatitis B surface antigen carriers treated with peginterferon alfa-2a

Li, Minghui; Xie, Yao; Lu, Zhigang; Lu, Yao; Shen, Ge; Wu, Shuling; Chang, Min; Mu, Cai-Qin; Hu, Leiping; Hua, Wenhao; Song, Shuangshuang; Zhang, Shufeng; Cheng, Jun; Xu, Da

doi:10.4254/wjh.v8.i15.637

Cited by 23 publications

(34 citation statements)

References 36 publications

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“…HBeAg seroconversion and HBsAg loss are two important clinical end‐points in treatment of CHB and predict improved survival with a markedly decreased risk for cirrhosis and HCC. HBsAg seroconversion is often considered the best measurable indicator of viral clearance and recovery, although the rate of HBsAg seroconversion, whether spontaneous or on antiviral therapy is rather low . Recent studies have indicated that a lower HBsAg level and HBV DNA level at baseline and older age may predict HBsAg loss .…”

Section: Discussionmentioning

confidence: 99%

Immune correlates of hepatitis B surface antigen spontaneous seroconversion in hepatitis B e antigen negative chronic hepatitis B patients

Vyas

Sharma

Sarin

et al. 2017

Liver International

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Background Hepatitis B surface antigen (HBsAg) seroconversion in HBeAg −ve chronic hepatitis B (CHB) infection is rare, possibly due to poor antigen processing and impaired humoral response. We investigated the role of dendritic cells (DCs), T follicular helper (TFH) cells and plasma B cells in seroconversion. Methods HBeAg −ve (n=135) CHB patients with raised ALT at baseline were followed up. Patients undergoing HBsAg seroconversion (Gr. I, n=11) were compared with non‐converters with low (Gr. II, n=17, HBV DNA<2000 IU/mL) or high HBV DNA (Gr. III, HBV DNA >2000 IU/mL, n=17). We measured cell phenotypes (TFH, B and DCs), HBV specific T‐cell functionality [using pooled overlapping surface and core peptides], IL21 levels and gene expression analysis by qRT‐PCR. Results Patients in Gr. I compared to Gr. II and III, had higher IL‐21 levels (865 vs 276 vs 111 pg/mL, P=<.0001), TFH (CD4+CXCR5+) cells (12.3 vs 4.67 vs 2.77, P=<.001), inducible T‐cell co‐stimulator (ICOS) expression on TFH cells (20.0 vs 13.0 vs 13.68, P=.01), HBsAg specific IL‐17 (9.40 vs 2.33 vs 2.61, P=<.001) and TNF‐α secreting TFH17 cells (82 vs 1.43 vs 2.33, P=<.001), plasma B (CD19+CD38+) cells (15.0 vs 5.08 vs 5.57, P=<.001), myeloid (17.80 vs 5.39 vs 2.70, P=<.001) and plasmocytoid DCs (2.6 vs 0.43 vs 0.21, P=<.001). Plasma B‐cell frequency (R2=.64, P=.01) and IL‐21 levels (R2=.52, P=.003) correlated with anti‐HBs titres in patients with HBsAg seroconversion. Conclusions Dendritic cell and TFH cell mediated responses regulate humoral responses against HBV and play a major role in HBsAg seroconversion in CHB patients.

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Section: Discussionmentioning

confidence: 99%

Immune correlates of hepatitis B surface antigen spontaneous seroconversion in hepatitis B e antigen negative chronic hepatitis B patients

Vyas

Sharma

Sarin

et al. 2017

Liver International

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“…Plasmacytoid dendritic cells (pDC) are the most important cells to connect innate and adaptive immune responses, and also the main source of interferon (IFN)-α. [ 4 ] IFN-α can suppress the activity of HBV enhancers,[ 5 ] control HBV-posttranscriptional replication,[ 6 7 8 ] and inhibit HBV nucleocapsid formation in virus replication. [ 9 ] It can also limit virus infection by modulating both innate and adaptive immunity, directly activate natural killer (NK) cells to enhance their cytotoxicity to eliminate-infected cells, promote the maturation of DCs, stimulate naive cluster of differentiation antigen 8+ (CD8+) T cells, resulting in clonal expansion and proliferation, and increase expression of chemokines that recruit NK, T and B cells to the site of infection.…”

Section: Introductionmentioning

confidence: 99%

Association of Cytokines with Alanine Aminotransferase, Hepatitis B Virus Surface Antigen and Hepatitis B Envelope Antigen Levels in Chronic Hepatitis B

Zhang

et al. 2018

Chinese Medical Journal

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Background:Cytokines play an important role in occurrence and recovery of hepatitis B virus (HBV) infection. The aim of this study was to investigate the changes of cytokines concentration and its correlation to alanine aminotransferase (ALT), HBV deoxyribonucleic acid (HBV-DNA), hepatitis B envelope antigen (HBeAg), and HBV surface antigen (HBsAg) in the development of chronic hepatitis B (CHB).Methods:Thirteen healthy individuals (HI), 30 chronic HBV-infected patients in immune tolerant (IT) phase, and 55 CHB patients were enrolled between August 2015 and May 2017. The peripheral blood samples were collected from all individuals. The levels of interferon (IFN)-α2, interleukin (IL)-10, transforming growth factor (TGF)-β1, HBV-DNA, HBsAg, and HBeAg and liver function were measured. The quantitative determinations of cytokines levels, including IFN-α2, IL-10, and TGF-β1 were performed using Luminex multiplex technology. The correlation of cytokines to ALT, HBV-DNA, HBsAg, and HBeAg was analyzed by linear regression analysis.Results:IFN-α2 levels were similar between HI and IT groups (15.35 [5.70, 67.65] pg/ml vs. 15.24 [4.07, 30.73] pg/ml, Z = −0.610, P = 0.542), while it elevated significantly in CHB group (35.29 [15.94, 70.15] pg/ml vs. 15.24 [4.07, 30.73] pg/ml; Z = −2.522, P = 0.012). Compared with HI group (3.73 [2.98, 11.92] pg/ml), IL-10 concentrations in IT group (5.02 [2.98, 10.11] pg/ml), and CHB group (7.48 [3.10, 18.00] pg/ml) slightly increased (χ2= 2.015, P = 0.365), and there was no significant difference between IT and CHB group (Z = −1.419, P = 0.156). The TGF-β1 levels among HI (3.59 ± 0.20 pg/ml), IT (3.62 ± 0.55 pg/ml), and CHB groups (3.64 ± 0.30 pg/ml) were similar (χ2= 2.739, P = 0.254). In all chronic HBV-infected patients (including patients in IT and CHB groups), the elevation of IFN-α2 level was significantly associated with ALT level (β= 0.389, t = 2.423, P = 0.018), and was also negatively correlated to HBV-DNA load (β = −0.358, t = −2.308, P = 0.024), HBsAg (β = −0.359, t = −2.288, P = 0.025), and HBeAg contents (β = −0.355, t = −2.258, P = 0.027). However, when both ALT level and cytokines were included as independent variable, HBV-DNA load, HBsAg, and HBeAg contents were only correlated to ALT level (β = −0.459, t = −4.225, P = 0.000; β = −0.616, t = −6.334, P = 0.000; and β = −0.290, t = −2.433, P = 0.018; respectively).Conclusions:IFN-α2 elevation was associated with ALT level in patients with chronic HBV infection. However, in CHB patients, only ALT level was correlated to HBV-DNA, HBsAg and HBeAg contents.

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“…Our study suggested that the activated pDC and the elevated IFN level could trigger the immune response against HBV in chronic hepatitis development from IT, and it might be the basis for those patients in immune active phase receiving PEG-IFN therapy to achieve a higher rate of HBeAg seroconversion and sustained response. [ 7 43 44 ] With the increasing of IL-10 and TGF-β2 contents in chronic hepatitis patients, it might limit virus clearance and lead low rate of spontaneous HBeAg seroconversion in nature history. [ 45 ]…”

Section: Discussionmentioning

confidence: 99%

“…IFN-α is an important antiviral active cytokine and widely used for the treatment of chronic HBV infection. [ 7 8 9 ] IFN-γ is the most important cytokine of cytotoxic T lymphocyte for controlling HBV replication or eradicating HBV in a noncytolyticmanner. [ 10 ] Fms-like tyrosine kinase 3 ligand (Flt-3L) is also an essential growth factor for DC cells and NK cells homeostasis in vivo .…”

Section: Introductionmentioning

confidence: 99%

Plasmacytoid Dendritic Cell Function and Cytokine Network Profiles in Patients with Acute or Chronic Hepatitis B Virus Infection

Zhang

et al. 2018

Chinese Medical Journal

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Background:Plasmacytoid dendritic cells (pDCs) and cytokines play an important role in occurrence and recovery of hepatitis B virus (HBV) infection. The aim of this study was to explore the frequency and function of pDC and serum cytokine network profiles in patients with acute or chronic HBV infection.Methods:The healthy individuals (HI group), hepatitis B envelope antigen (HBeAg)-positive chronic HBV patients in immune tolerance (IT) phase (IT group), HBeAg-positive chronic HBV patients (CHB group), and acute HBV patients (AHB group) were enrolled in this study. The frequency of cluster of differentiation antigen 86 (CD86) + pDC and the counts of CD86 molecular expressed on surface of pDC were tested by flow cytometer. The quantitative determinations of cytokines, including Fms-like tyrosine kinase 3 ligand (Flt-3L), interferon (IFN)-α2, IFN-γ, interleukin (IL)-17A, IL-6, IL-10, transforming growth factor (TGF)-β1 and TGF-β2, were performed using Luminex multiplex technology.Results:In this study, there were 13 patients in HI group, 30 in IT group, 50 in CHB group, and 32 in AHB group. Compared with HI group, HBV infected group (including all patients in IT, CHB and AHB groups) had significantly higher counts of CD86 molecular expressed on the surface of pDC (4596.5 ± 896.5 vs. 7097.7 ± 3124.6; P < 0.001). The counts of CD86 molecular expressed on the surface of pDC in CHB group (7739.2 ± 4125.4) was significantly higher than that of IT group (6393.4 ± 1653.6, P = 0.043). Compared with IT group, the profile of cytokines of Flt-3L, IFN-γ, and IL-17A was decreased, IFN-α2 was significantly increased (P = 0.012) in CHB group. The contents of IL-10, TGF-β1, and TGF-β2 in AHB group were significantly increased compared with IT and CHB groups (all P < 0.05).Conclusions:This study demonstrated that the function of pDC was unaffected in HBV infection. The enhanced function of pDC and IFN-α2 might involve triggering the immune response from IT to hepatitis active phase in HBV infection. Acute patients mainly presented as down-regulation of the immune response by enhanced IL-10 and TGF-β.

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Hepatitis B surface antigen clearance in inactive hepatitis B surface antigen carriers treated with peginterferon alfa-2a

Abstract: IFN treatment results in HBsAg loss and seroconversion in a considerable proportion of inactive HBsAg carriers with low HBsAg concentrations.

Cited by 23 publications

References 36 publications

Immune correlates of hepatitis B surface antigen spontaneous seroconversion in hepatitis B e antigen negative chronic hepatitis B patients

Immune correlates of hepatitis B surface antigen spontaneous seroconversion in hepatitis B e antigen negative chronic hepatitis B patients

Association of Cytokines with Alanine Aminotransferase, Hepatitis B Virus Surface Antigen and Hepatitis B Envelope Antigen Levels in Chronic Hepatitis B

Plasmacytoid Dendritic Cell Function and Cytokine Network Profiles in Patients with Acute or Chronic Hepatitis B Virus Infection

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