scholarly journals Effects of HBeAg Status on cellular immune function of patients with Hepatitis B virus/Treponema Pallidum Co-infection

2021 ◽  
Vol 37 (7) ◽  
Author(s):  
Wei Luo ◽  
Hanxiao Xin ◽  
Pengyun Zhao ◽  
Shasha Jiang

Objectives: This study was aimed at exploring the effects of hepatitis B envelope antigen (HBeAg) status on the cellular immune function of patients with hepatitis B virus/treponema pallidum (HBV/TP) co-infection. Methods: The clinical data of 79 patients with HBV/TP co-infection admitted to our hospital from January 2019 to January 2020 were retrospectively analyzed. These patients were divided into two groups according to the different HBeAg statuses before the treatment: 41 HBeAg+ patients were included in the HBeAg+ group, while 38 HBeAg- patients were included in the HBeAg- group. The levels of HBV-DNA, T lymphocyte subsets represented by NK cells and cytokines associated with T cells in the peripheral blood (PB) of the patients were compared between both groups. Results: The HBV-DNA levels in the HBeAg+ group were significantly higher than those in the HBeAg- group (P < 0.05). The levels of CD3+, CD4+, CD4+/CD8+ and natural killer (NK) cells in the HBeAg+ group were higher than those in the HBeAg- group (P < 0.05), while the levels of CD8+ cells were lower than those in the HBeAg- group (P < 0.05). Moreover, the levels of interferon-γ (IFN-γ), tumor necrosis factor (TNF-α), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-17 (IL-17), transforming growth factor-β (TGF-β) in the HBeAg+ group were all significantly higher than those in the HBeAg- group (P < 0.05), but there was no significant difference in the levels of interleukin-4 (IL-4) and interleukin-10 (IL-10) between the HBeAg+ group and the HBeAg- group (P > 0.05). Conclusion: HBeAg+ can increase the HBV-DNA levels in the PB of patients with HBV/TP co-infection, in turn triggering the body to initiate cellular immunity, increasing the levels of T lymphocyte subsets, and promote the secretion of cytokines. doi: https://doi.org/10.12669/pjms.37.7.4253 How to cite this:Luo W, Xin H, Zhao P, Jiang S. Effects of HBeAg Status on cellular immune function of patients with Hepatitis B virus/Treponema Pallidum Co-infection. Pak J Med Sci. 2021;37(7):---------. doi: https://doi.org/10.12669/pjms.37.7.4253 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

2012 ◽  
Vol 1 (2) ◽  
pp. 84-90 ◽  
Author(s):  
Qing He ◽  
Qi-yuan Tang ◽  
Xiao-hua Le ◽  
De-liang Lv ◽  
Xiang-mei Zhang ◽  
...  

Abstract Objective The clinical significance of differential distribution of hepatitis B virus (HBV) nucleocapsid antigen in hepatocytes remains unknown. The goal of this study is to determine the relationship between distinct HBV core antigen distribution pattern and alanine transaminase (ALT), liver histological inflammatory activity grades, serum HBeAg status and HBV DNA level.Methods Total of 958 cases with chronic hepatitis B were recruited into this study. Liver function tests, serum HBV DNA level, serological HBV markers and liver immunohistochemistry were examined according to the conventional instructions. Chi Square tests were performed to analyze the differences among these groups.Results It was found that 552 (58%) cases were tested positive for HBV core antigen by immunohistochemical staining. Cytoplasmic hepatitis B core antigen (HBcAg) expression correlated with ALT level and serum HBV DNA and liver inflammatory activity scores, however, nuclear HBcAg expression in hepatocytes was associated with normal ALT level, lower liver inflammatory activity score and higher serum HBV DNA level and rate of HBeAg positivity. Both nuclear and cytoplasmic HBcAg expression in hepatocytes associated with a middle ALT level and liver inflammatory activity score, higher rate of serum detectable HBeAg and a higher HBV DNA level. However, undetectable core antigen was related to a lower ALT level and histological inflammatory activity grade, lower positive HBeAg rate and HBV DNA level.Conclusions Undetectable liver HBcAg is associated with HBV clearance, ALT normalization and hepatitis B e antigen (HBeAg) seroconversion, and cytoplasmic HBcAg expression associated with higher hepatic inflammatory activity. However, nuclear HBcAg expression correlates with immune tolerance characterized with normal ALT and lower liver inflammatory activity, higher HBV replication level and higher rate of HBeAg positivity.


2019 ◽  
Author(s):  
Shan Fu ◽  
NaiJuan Yao ◽  
YaLi Feng ◽  
Juan Li ◽  
YuChao Wu ◽  
...  

Abstract Background: There isn’t consensus about the optimal dose of hepatitis B immunoglobulin (HBIG) in combination with hepatitis B vaccine to preventing mother-to-child transmission (MTCT) of hepatitis B virus(HBV).Methods: We systematically searched MEDLINE, Embase, and Cochrane Library from database inception to Jan 16, 2019 for studies. The primary outcome was HBsAg and/or HBV DNA positive in infants at 6-12 months old. We performed a meta-analysis with a random-effects model to calculate a pooled estimate of MTCT.Results: We included 31 studies, comprising of 12151 infants. There wasn't significant differences in the pooled MTCT rates between 100 IU HBIG group and 200 IU HBIG group (5% vs 5%, P = 0.757). When further stratified according to HBeAg status, in HBeAg(+) mothers, 7% (95%CI 4%-11%) infants became chronic HBV infection in 100 IU HBIG group compared to 7% (95%CI 5%-9%)in 200 IU group. The rates were 1% (95%CI 0%-2%) in 100IU group and 0% (95%CI 0%-1%) in 200IU group in infants born to HBeAg(-) mothers, respectively. When further comparing MTCT in infants from mothers with HBV DNA≥1×10^6 IU/mL, the pooled MTCT rate was 12% (95%CI 7%-17%) in 100IU group and 8% (95%CI 5%-13%) in 200IU group, respectively. In addition, comparative analysis of four studies concerning two different dosages of HBIG further manifested the comparability.Conclusion: 100 IU HBIG is sufficient in preventing MTCT for infants from chronic hepatitis B infected mothers, regardless of maternal HBeAg status or viral load.


2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A297-A297
Author(s):  
Fu-Sheng Wang ◽  
Fanping Meng ◽  
Jiehua Jin ◽  
Yuanyuan Li ◽  
Regina Wanju Wong ◽  
...  

BackgroundWe have demonstrated the ability of Hepatitis-B-virus (HBV)-specific T cell receptor (TCR) bioengineered T cells to recognize and lyse Hepatocellular carcinoma (HCC) cells expressing HBV antigens derived from HBV-DNA integration in patients with liver transplant.1 LioCyx-M is an immunotherapeutic product composing of autologous T cells transiently modified with in-vitro transcribed mRNA encoding HBV-specific TCR. The transient TCR expression makes LioCyx -M amenable to a dose escalating posology.MethodsThe primary endpoint of this phase 1 trial is to assess the safety and tolerability of LioCyx-M in patients with advanced HBV-HCC without curative treatment options. Eligible patients were diagnosed with Barcelona clinic liver cancer stage B or C HCC (Child-Pugh < 7 points), receiving >1 year antiviral treatment prior to enrollment. These patients had matching HLA class I genotypes which present HBV encoded antigen. Peripheral blood was collected from each patient prior to each dose for LioCyx-M manufacturing. Patients received 4 escalating doses of 1×104 cells/kg, 1×105 cells/kg, 1×106 cells/kg, 5×106 cells/kg bodyweight (BW) in the first treatment cycle, each intravenously administered weekly. Patients underwent 1-month safety assessment post the 4th infusion, according to Common Terminology NCI CTCAE Version 4.0.3. If there were no dose associated toxicities, patients were eligible to continue administration of LioCyx-M at dose of 5 × 106 cells/kg BW weekly. Tumor response per RECIST 1.1 criteria and survival time were assessed.ResultsAt data cutoff (30 April 2020), eight patients were enrolled, with a median age of 53 (range: 49 - 67). These patients received a median number of 6 (range: 4 - 12) infusions of LioCyx-M. 1 patient developed Grade 3 elevations in alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST) and bilirubin after receiving LioCyx-M at dose level of 1×105 cells/kg BW. Another patient had Grade 1 transient fever after receiving LioCyx-M at dose level 5×106 cells/kg BW in the 4th, 5th and 6th infusions. No treatment-related adverse events (trAEs) such as cytokine release syndrome or neurotoxicity were observed. No fatal trAEs were observed. The median time to progression was 1.9 months (range: 0.2 - 9.5 months). The median overall survival was 34 months (range: 3 - 38.2 months).ConclusionsThe encouraging clinical outcome and tolerable safety highlight the good benefit-risk profile of LioCyx-M. Therefore, further exploration of efficacy of LioCyx-M treatment for advanced HBV-HCC is warranted in a Phase 2 proof-of-concept clinical study.AcknowledgementsFunding: Lion TCR.Trial RegistrationNCT03899415Ethics ApprovalThe study was approved by Fifth Medical Center of Chinese PLA General Hospital’s Ethics Board, approval number R2016185DI010.ReferenceTan AT, Yang N, Lee Krishnamoorthy T, et al. Use of Expression Profiles of HBV-DNA Integrated Into Genomes of Hepatocellular Carcinoma Cells to Select T Cells for Immunotherapy. Gastroenterology 2019;156(6):1862–1876.e9.


2008 ◽  
Vol 12 ◽  
pp. e415
Author(s):  
Z.L. Wu ◽  
X.D. Lu ◽  
X.Q. Zhong ◽  
L.F. Ling ◽  
G. Lin ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Oluyinka Oladele Opaleye ◽  
Adeolu Sunday Oluremi ◽  
Adetona Babatunde Atiba ◽  
Moses Olubusuyi Adewumi ◽  
Olatunji Victor Mabayoje ◽  
...  

HIV has been known to interfere with the natural history of hepatitis B virus (HBV) infection. In this study we investigate the prevalence of occult hepatitis B virus infection (OBI) among HIV-infected individuals in Nigeria. Overall, 1200 archived HIV positive samples were screened for detectable HBsAg using rapid technique, in Ikole Ekiti Specialist Hospital. The HBsAg negative samples were tested for HBsAg, anti-HBc, and anti-HCV by ELISA. Polymerase chain reaction was used for HBV DNA amplification and CD4 counts were analyzed by cytometry. Nine hundred and eighty of the HIV samples were HBsAg negative. HBV DNA was detected in 21/188 (11.2%) of patients without detectable HBsAg. CD4 count for the patients ranged from 2 to 2,140 cells/μL of blood (mean = 490 cells/μL of blood). HCV coinfection was detected only in 3/188 (1.6%) of the HIV-infected patients (P>0.05). Twenty-eight (29.2%) of the 96 HIV samples screened were positive for anti-HBc. Averagely the HBV viral load was <50 copies/mL in the OBI samples examined by quantitative PCR. The prevalence of OBI was significantly high among HIV-infected patients. These findings highlight the significance of nucleic acid testing in HBV diagnosis in HIV patients.


2004 ◽  
Vol 48 (6) ◽  
pp. 2199-2205 ◽  
Author(s):  
Radhakrishnan P. Iyer ◽  
Yi Jin ◽  
Arlene Roland ◽  
John D. Morrey ◽  
Samir Mounir ◽  
...  

ABSTRACT Several nucleoside analogs are under clinical development for use against hepatitis B virus (HBV). Lamivudine (3TC), a nucleoside analog, and adefovir dipivoxil (ADV), an acyclonucleotide analog, are clinically approved. However, long-term treatment can induce viral resistance, and following the cessation of therapy, viral rebound is frequently observed. There continues to be a need for new antiviral agents with novel mechanisms of action. A library of more than 600 di- and trinucleotide compounds synthesized by parallel synthesis using a combinatorial strategy was screened for potential inhibitors of HBV replication using the chronically HBV-producing cell line 2.2.15. Through an iterative process of synthesis, lead optimization, and screening, three analogs were identified as potent inhibitors of HBV replication: dinucleotides ORI-7246 (drug concentration at which a 10-fold reduction of HBV DNA was observed [EC90], 1.4 μM) and ORI-9020 (EC90, 1.2 μM) and trinucleotide ORI-7170 (EC90, 7.2 μM). These analogs inhibited the replication of both strands of HBV DNA. No suppression of HBV protein synthesis or intracellular core particle formation by these analogs was observed. No inhibition of HBV DNA strand elongation by the analogs or their 5′-triphosphate versions was apparent in in vitro polymerase assays. Although the exact mechanism of action is not yet identified, present data are consistent with an inhibition of the HBV reverse transcriptase-directed priming step prior to elongation of the first viral DNA strand. In transient-transfection assays, these analogs inhibited the replication of 3TC-resistant HBV. Synergistic interactions in combination treatments between the analogs and either 3TC or ADV were observed. These compounds represent a novel class of anti-HBV molecules and warrant further investigation as potential therapeutic agents.


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