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

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.

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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

10.21203/rs.2.16041/v3 ◽

2020 ◽

Author(s):

Ruyu Liu ◽

Yanhui Chen ◽

Jiang Guo ◽

Minghui Li ◽

Yao Lu ◽

...

Keyword(s):

T Cells ◽

Chronic Hepatitis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Cd8 T Cells ◽

Mononuclear Cells ◽

Hbeag Seroconversion ◽

Median Frequency ◽

Inflammation Response ◽

Significant Difference

Abstract Background: 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.

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The Reduction in CD8+PD1+ T Cells in Liver Histological Tissue is Related to Pegylated IFN-α Therapy Outcomes in Chronic Hepatitis B Patients

10.21203/rs.2.16041/v1 ◽

2019 ◽

Author(s):

Ruyu Liu ◽

Yanhui Chen ◽

Jiang Guo ◽

Minghui Li ◽

Yao Lu ◽

...

Keyword(s):

T Cells ◽

Chronic Hepatitis ◽

Hepatitis B ◽

Antiviral Therapy ◽

Cd8 T Cells ◽

Mononuclear Cells ◽

Hbeag Seroconversion ◽

Therapy Outcomes ◽

Inflammation Response ◽

Significant Difference

Abstract Background and Aim Antiviral therapy for patients with immune-active chronic hepatitis B (CHB) should be adopted to decrease the risk of liver-related complications. While antiviral therapy outcomes of PEG-IFN-α vary in different CHB patients. We aimed to identify the factors influencing antiviral therapy outcomes in CHB patients who received PEG-IFN-α therapy.Methods Thirty-two CHB patients who received PEG-IFN-α therapy were enrolled in this study. All of the patients underwent two liver biopsies at baseline and 6 months later. CD8 + T cells, CD4 + T cells, CD68 + mononuclear cells, and PD-1 levels in 64 liver biopsy specimens were tested via immunofluorescence.Results CD8 + T cells in 32 CHB patients’ liver tissue significantly decreased after 6 months of PEG-IFN-α therapy (p<0.01). CD8 + PD1 + T cells significantly decreased after 6 months of PEG-IFN-α treatment in the FIER (fibrosis and inflammation response with HBeAg seroconversion) group (p<0.05), while CD8 + PD1 - T cells had no significant difference. However, in the FIENR (no fibrosis and inflammation response and HBeAg seroconversion) group, CD8 + PD1 - T cells significantly decreased after 6 months of PEG-IFN-α treatment (p<0.05), while CD8 + PD1 + T cells had no significant difference. CD68 + mononuclear cells at baseline were higher in the FIRENR (fibrosis and inflammation response without HBeAg seroconversion) group than the FIENR (no fibrosis and inflammation response and HBeAg seroconversion) group.Conclusions The reduction in CD8 + PD1 + T cells in liver tissue was critical for patients who responded to PEG-IFN-α therapy. High levels of CD68 + mononuclear cells at baseline might be associated with fibrosis and inflammation response to PEG-IFN-α therapy.

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TIM-3 as a marker of exhaustion in CD8+ T cells of active chronic hepatitis B patients

Microbial Pathogenesis ◽

10.1016/j.micpath.2019.01.026 ◽

2019 ◽

Vol 128 ◽

pp. 323-328 ◽

Cited By ~ 8

Author(s):

Hiva Mohammadizad ◽

Mehdi Shahbazi ◽

Mohammad Reza Hasanjani Roushan ◽

Mehdi Soltanzadeh-Yamchi ◽

Mousa Mohammadnia-Afrouzi

Keyword(s):

T Cells ◽

Chronic Hepatitis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Cd8 T Cells ◽

Active Chronic Hepatitis

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Kushenin Combined with Nucleos(t)ide Analogues for Chronic Hepatitis B: A Systematic Review and Meta-Analysis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/529636 ◽

2015 ◽

Vol 2015 ◽

pp. 1-12 ◽

Cited By ~ 2

Author(s):

Zhe Chen ◽

Xiao Ma ◽

Yanling Zhao ◽

Jiabo Wang ◽

Yaming Zhang ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Meta Analysis ◽

Hbeag Seroconversion ◽

Low Frequency ◽

Hbv Dna ◽

Significant Difference ◽

Undetectable Serum ◽

One Year

Objective. To evaluate the efficacy and safety of Kushenin (KS) combined with nucleoside analogues (NAs) for chronic hepatitis B (CHB).Methods. Randomized controlled trials (RCTs) of KS combined with NAs for CHB were identified through 7 databases. Frequencies of loss of serum HBeAg, HBeAg seroconversion, undetectable serum HBV-DNA, ALT normalization, and adverse events at 48 weeks were abstracted by two reviewers. The Cochrane software was performed to assess the risk of bias in the included trials. Data were analyzed with Review Manager 5.3 software.Results. 18 RCTs involving 1684 subjects with CHB were included in the analysis. KS combined with NAs including lamivudine (LAM), entecavir (ETV), adefovir dipivoxil (ADV), and telbivudine (TLV) showed different degree of improvement in CHB indices. KS combined with NAs increased the frequency of loss of serum HBeAg, HBeAg seroconversion, undetectable HBV-DNA levels, and ALT normalization compared with single agents. It also decreased serum ALT and AST level after one-year treatment. However, KS combined with TLV did not show a significant difference in CHB indices. The side-effects of KS combined with NAs were light and of low frequency.Conclusion. KS combined with NAs improves the efficacy of NAs in CHB.

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Efficacy Comparison of Tenofovir and Entecavir in HBeAg-Positive Chronic Hepatitis B Patients with High HBV DNA

BioMed Research International ◽

10.1155/2016/6725073 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 8

Author(s):

Hong Shi ◽

Mingxing Huang ◽

Guoli Lin ◽

Xiangyong Li ◽

Yuankai Wu ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Adverse Reactions ◽

Treated Patient ◽

Hbeag Seroconversion ◽

Total Duration ◽

Hbv Dna ◽

Significant Difference ◽

Positive Chronic Hepatitis

Objectives. To compare entecavir (ETV) and tenofovir disoproxil fumarate (TDF) effects in chronic hepatitis B (CHB) patients with high HBV DNA.Method. 96 patients treated initially with tenofovir (TDF group) or entecavir (ETV group) were included in this retrospective study. The following parameters were assessed: HBeAg and hepatitis B e antibody (anti-HBe) status, serum alanine aminotransferase (ALT), and HBV-DNA levels at weeks 4, 12, 24, 36, 48, 60, 72, and 96; time to ALT normalization, undetectable HBV-DNA levels, and HBeAg seroconversion; total duration of follow-up and adverse reactions.Results. The patients included 66 (69%) and 30 (31%) individuals administered ETV and TDF, respectively, comprising 75% males. They were35.1±4.5and33.7±4.6years old in ETV and TDF groups, respectively. At 36 weeks, the response rate was significantly higher in the TDF group than in ETV treated patients (90% versus 69.7%,p=0.03). At 48 weeks, less patients administered ETV showed undetectable HBV-DNA levels compared with the TDF group (86.4% versus 96.7%), a non-statistically significant difference (p=0.13). Only 1 ETV treated patient developed virological breakthrough at 48–96 w. No adverse reactions were found.Conclusion. ETV and TDF are comparable in efficacy and safety to suppress HBV-DNA replication in HBeAg-positive CHB patients with high HBV DNA.

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Laboratory Evaluation of Three Regimens of Treatment of Chronic Hepatitis B: Tenofovir, Entecavir and Combination of Lamivudine and Adefovir

Journal of Laboratory Physicians ◽

10.4103/0974-2727.98664 ◽

2012 ◽

Vol 4 (01) ◽

pp. 010-016 ◽

Cited By ~ 13

Author(s):

Rajeswari Jayakumar ◽

Yogendra Kumar Joshi ◽

Sarman Singh

Keyword(s):

Chronic Hepatitis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Hbeag Seroconversion ◽

Hbv Dna ◽

Laboratory Evaluation ◽

Significant Difference ◽

Life Threatening ◽

A Prospective Study ◽

Hbeag Status

ABSTRACT Background: Chronic hepatitis B is a disease of concern due to its life-threatening complications like cirrhosis, and hepatocellular carcinoma (HCC) in 20-40% of patients. There are about 400 million people affected worldwide with HBV, and over 300,000 die every year from HBV-related diseases. Oral antivirals like lamivudine, adefovir, entecavir, and tenofovir are commonly used to treat chronic hepatitis B. In this study, we tried to evaluate the comparative efficacy of these drugs alone and in combination. Materials and Methods: Chronic hepatitis B patients with HBV-DNA more than 104 Copies/mL irrespective of their HBeAg status (n = 60) were enrolled in a prospective study. 21, 20, and 19 patients were treated with lamivudine (100 mg/day) plus adefovir (10 mg/day) combination entecavir monotherapy (0.5 mg/day) and tenofovir monotherapy (300 mg/day), respectively and were followed up for 24 weeks with their virological, serological, and biochemical markers measured at 12 and 24 weeks. Results: After 24 weeks of treatment, there was no significant difference between the 3 groups in suppressing HBV-DNA to undetectable levels. The median decrease in HBV-DNA levels from baseline was better with tenofovir and entecavir monotherapies than lamivudine and adefovir combination, which was statistically significant. There was no significant difference between the 3 groups in HBsAg and HBeAg seroconversion and normalization of biochemical parameters. Conclusion: Entecavir and tenofovir monotherapy were found to be more effective than lamivudine plus adefovir combination in reducing the HBV-DNA levels. However, lamivudine plus adefovir combination was not too inferior, especially when cost of treatment was taken into consideration.

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