scholarly journals Genotyping of immune-related loci associated with delayed HBeAg seroconversion in immune-active chronic hepatitis B patients

2020 ◽  
Vol 176 ◽  
pp. 104719
Author(s):  
Wen-Chun Liu ◽  
I-Chin Wu ◽  
Yen-Cheng Chiu ◽  
Kuo-Chih Tseng ◽  
Chi-Yi Chen ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Hbeag Seroconversion ◽  
Active Chronic Hepatitis

scholarly journals The Reduction in CD8+PD-1+ T Cells in Liver Histological Tissue is Related to Pegylated IFN-α Therapy Outcomes in Chronic Hepatitis B Patients

2020 ◽  
Author(s):  
Ruyu Liu ◽  
Yanhui Chen ◽  
Jiang Guo ◽  
Minghui Li ◽  
Yao Lu ◽  
...  
Keyword(s):  
T Cells ◽  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Mononuclear Cells ◽  
Hbeag Seroconversion ◽  
Active Chronic Hepatitis ◽  
Median Frequency ◽  
Inflammation Response ◽  
Significant Difference

Abstract Background and Aim: Antiviral therapy is recommended for patients with immune-active chronic hepatitis B (CHB) to decrease the risk of liver-related complications. However, the outcomes of the pegylated IFN-α (PEG-IFN-α) therapy vary among CHB patients. We aimed to identify factors that can influence the outcomes in CHB patients who received antiviral PEG-IFN-α monotherapy. Methods: Thirty-two CHB patients who received PEG-IFN-α monotherapy were enrolled in this study. All of the patients underwent two liver biopsies at baseline and 6 months after the initiation of the therapy. CD8+ T cells, CD4+ T cells, CD68+ mononuclear cells, and PD-1 levels in the 64 liver biopsy specimens were examined via immunofluorescence. Results: The overall median frequency of CD8+ T cells in the liver tissues of 32 CHB patients significantly decreased at 6 months after the therapy initiation (p < 0.01). In the FIER (fibrosis and inflammation response with HBeAg seroconversion) group, CD8+PD-1+ T cells significantly decreased at 6 months (p < 0.05), while CD8+PD-1- T cells had no significant difference. On the contrary, in the FIENR (no fibrosis and inflammation response and HBeAg seroconversion) group, CD8+PD-1- T cells significantly decreased after 6 months of PEG-IFN-α treatment (p < 0.05), while CD8+PD-1+ T cells had no significant difference. In addition, the levels of CD68+ mononuclear cells in the FIER group showed an overall increasing trend after treatment (p < 0.05). Conclusions: The changes in the levels of CD8+PD-1+ T cells and CD68+ mononuclear cells may be related to the response to PEG-IFN-α therapy.

scholarly journals High-Throughput Analysis of the T Cell Receptor Beta Chain Repertoire in PBMCs from Chronic Hepatitis B Patients with HBeAg Seroconversion

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Yachao Qu ◽  
Yong Huang ◽  
Di Liu ◽  
Yinuo Huang ◽  
Zhiyi Zhang ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Hbeag Seroconversion ◽  
Cell Receptor ◽  
High Throughput Analysis ◽  
Before And After ◽  
T Cell Receptor Beta

T lymphocytes are the most important immune cells that affect both the development and treatment of hepatitis B. We used high-throughput sequencing to determine the diversity in the V and J regions of the TCRβchain in 4 chronic hepatitis B patients before and after HBeAg seroconversion. Here, we demonstrate that the 4 patients expressedVβ12-4 at the highest frequencies of 10.6%, 9.2%, 17.5%, and 7.5%, andVβ28was the second most common, with frequencies of 7.8%, 6.7%, 5.3%, and 10.9%, respectively. No significant changes were observed following seroconversion. With regard to the Jβgene, Jβ2-1 was the most commonly expressed in the 4 patients at frequencies of 5.8%, 6.5%, 11.3%, and 7.3%, respectively. Analysis of the V-J region genes revealed several differences, including significant increases in the expression levels of V7-2-01-J2-1, V12-4-J1-1, and V28-1-J1-5 and a decrease in that of V19-01-J2-3. These results illustrate the presence of biased TCRVβand Jβgene expression in the chronic hepatitis B patients. TRBVβ12-4,Vβ28, Jβ2-1, V7-2-01-J2-1, V12-4-J1-1, and V28-1-J1-5 may be associated with the development and treatment of CHB.

Long-term serological, virological and histological responses to RNA inhibition by ARC-520 in Chinese chronic hepatitis B patients on entecavir treatment

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323445
Author(s):  
Man-Fung Yuen ◽  
Danny Ka-Ho Wong ◽  
Thomas Schluep ◽  
Ching-Lung Lai ◽  
Carlo Ferrari ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Hbeag Seroconversion ◽  
Positive Staining ◽  
Viral Antigens ◽  
Chronic Hepatitis B Virus ◽  
Hbsag Seroclearance ◽  
Hbsag Seroconversion

ObjectiveWe examined the serological, virological (in serum and liver) and histological profiles in chronic hepatitis B virus (HBV) patients during and after completion of multiple dose (MD) ARC-520.DesignThe present phase 1b study was a multidose, open-label extension cohort of patients that had received single dose ARC-520 in our previous study. Eight patients received 4–9 4 weekly doses of MD ARC-520 and entecavir. Liver biopsies were performed in six patients. Intrahepatic and serum HBV DNA, HBV RNA and viral antigens were measured.ResultsAll patients had 28.9–30.4 months of follow-up after the last MD. All three hepatitis B e antigen (HBeAg)-positive patients had profound reductions in hepatitis B surface antigen (HBsAg), HBeAg, hepatitis B core-related antigen and HBV RNA with two undergoing HBeAg seroconversion. One further achieved HBsAg seroconversion (anti-HBs level of 25.1 IU/L) and the remaining two had HBsAg reductions of −1.7 and −3.5 log IU/mL >30 months after MD. Among the five HBeAg-negative patients, four had modest HBsAg reduction >29 months after completion of MD and one achieved HBsAg seroconversion (anti-HBs level of 152.5 IU/L) and was negative for liver HBsAg staining. Entecavir was successfully stopped in this patient 12 months after HBsAg seroconversion. Temporally related alanine aminotransferase elevations preceded by HBsAg reductions were observed in three patients suggesting immune activation. HBcAg staining was negative in all six biopsied patients. Two patients with <10% HBsAg positive staining of hepatocytes had correspondingly low serum HBsAg levels of 1.5 and 11.5 IU/mL.ConclusionsMD ARC-520 therapy achieved sustained and profound reductions of viral antigens and HBV RNA. HBsAg seroclearance was achievable.Trial registration numberNCT02065336.

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