Immunotherapy for hepatitis B in the direct acting antiviral era: Reevaluating the thymosin α1 efficacy trials in the light of a combination therapy approach

Naylor, Paul; Mutchníck, Milton G.

doi:10.1111/jvh.12807

Cited by 23 publications

(19 citation statements)

References 37 publications

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“…In vitro experiments showed that Tα1 induced the maturation of thymocytes, stimulated differentiation into active T cells and functional recovery of T cells [32]. In vivo experiments verified that Tα1 was associated with the up-regulating activity of natural killer cell in CHB patients [8]. Our results demonstrated that ETV plus Tα1 combination therapy could provide additional benefits of the virological and serological response over ETV monotherapy, which is accorded with previous studies.…”

Section: Discussionsupporting

confidence: 89%

“…Meanwhile, cirrhosis is also accompanied with serious immunodysfunction, which parallelly presents chronic systemic inflammation and immune inhibition [6]. The present mainstay of HBV treatment is the repression of HBV replication by nucleos(t)ide analogs (NAs), such as entecavir (ETV), lamivudine (LAM) and tenofovir disoproxil fumarate (TDF), and supplementing with the immune-mediated agents such as α-Interferon and Tα1 [7,8]. Theoretically, the strong immune response is conducive to viral suppression and clearance.…”

Section: Introductionmentioning

confidence: 99%

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The Clinical Efficacy and Adverse Effects of Entecavir plus Thymosin alpha-1 Combination Therapy versus Entecavir Monotherapy in HBV-related Cirrhosis: A Systematic Review and Meta-analysis

Peng

Huang

et al. 2020

Preprint

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Background Previous studies have demonstrated the benefits of thymosin alpha-1 (Tα1) in anti-virus, immunological enhancement and anti-inflammation. However, it is controversial about the efficacy and safety of entecavir (ETV) plus Tα1 combination therapy versus ETV monotherapy in cirrhosis patients with hepatitis B virus (HBV) infection. Objective The systematic review and meta-analysis of randomized clincal trials (RCTs) were performed to evaluate the efficacy and safety of ETV plus Tα1 compared with ETV monotherapy in HBV-related cirrhosis. Methods A systematic search was performed via PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journals Database (VIP), and Chinese Biological Medicine database (CBM). Relative risk (RR) and standardized mean difference (SMD) with a fixed- or random- effect model were calculated. Heterogeneity were assessed with the Cochrane Q-test and I 2 values. Results Seven RCTs involving 1144 subjects were included in the systematic review and meta-analysis. Compared with ETV monotherapy, ETV plus Tα1 combination therapy led to a higher complete response (RR = 1.18; 95% CI, 1.07 - 1.30). The HBV DNA undetectable rate and HBeAg loss rate of ETV plus Tα1 therapy for 24 weeks was higher than the ETV alone (RR = 1.91; 95% CI, 1.56 - 2.35; RR = 2.05; 95% CI, 1.62 - 2.60). However, after treatment for 48 and 52 weeks, there was no significantly different between the combination therapy and ETV monotherapy (RR = 1.07; 95% CI, 0.96 - 1.18; RR = 1.17; 95% CI, 0.89 - 1.55). In comparison with ETV alone, ETV plus Tα1 improved part of biochemical parameters and liver fibrosis. There was significant heterogeneity. In addition, The ETV plus Tα1 significantly reduced adverse events compared to ETV monotherapy (RR = 0.48; 95% CI, 0.24 - 0.95). Conclusions ETV plus Tα1 combination therapy might have a higher clinical response and a lower comprehensive adverse reaction rate in HBV-related cirrhosis patients compared with ETV monotherapy. Meanwhile, the whole patients included in this meta-analysis were from chinese mainland, so that more worldwide RCTs with a large sample size are needed to verify the current findings.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

The Clinical Efficacy and Adverse Effects of Entecavir plus Thymosin alpha-1 Combination Therapy versus Entecavir Monotherapy in HBV-related Cirrhosis: A Systematic Review and Meta-analysis

Peng

Huang

et al. 2020

Preprint

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“…It was showed in vitro experiments that Tα1 could inhibit the production of in ammatory cytokines such as TNF-α and potentiate immunocellular function via inducing the maturation of T-cells and up-regulation of CD4+, CD8+ T cells and natural killer (NK) cells [32]. It was veri ed in vivo experiments that Tα1 was associated with the activation of NK cells in patients with CHB [8]. Our results demonstrated that ETV plus Tα1 combination therapy could provide additional bene ts in the inhibition of HBV DNA and negative conversion of HBeAg over ETV monotherapy, but the negative conversion rate of HBsAg was similar between the 2 treatment approaches.…”

Section: Discussionmentioning

confidence: 99%

The Clinical Efficacy and Adverse Effects of Entecavir plus Thymosin alpha-1 Combination Therapy versus Entecavir Monotherapy in HBV-related Cirrhosis: A Systematic Review and Meta-analysis

Peng

Huang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Previous studies have demonstrated the benefits of thymosin alpha-1 (Tα1) in anti-virus, immunological enhancement and anti-inflammation. However, it is controversial about the efficacy and safety of entecavir (ETV) plus T α1 combination therapy versus ETV monotherapy in cirrhotic patients with hepatitis B virus (HBV) infection. Methods The systematic review and meta-analysis of randomized clinical trials (RCTs) were performed to evaluate the efficacy and safety of ETV plus Tα1 combination therapy versus ETV monotherapy in HBV -related patients with cirrhosis. We performed a systematic literature search on seven databases. Relative risk (RR) and standardized mean difference (SMD) with a fixed- or random- effect model were calculated. Heterogeneity was assessed through a Cochrane Q-test and I 2 values. Results Seven RCTs involving 1144 subjects were included in the systematic review and meta-analysis. Compared with ETV monotherapy, ETV plus Tα1 combination therapy led to a higher complete response. In post treatment for 24 weeks, the HBV DNA undetectable rate and HBeAg loss rate were higher in ETV plus Tα1 group than in ETV alone group. However, after 48 and 52 weeks of treatment, there was no significant difference between the combination therapy and ETV monotherapy. At week 52 of treatment, the HBsAg loss rate of ETV plus Tα1 group was no significance with that of ETV alone group. In comparison with ETV alone, the some biochemical parameters and liver fibrosis were obviously improved by ETV plus Tα1 , and there was significant heterogeneity. In addition, the number of adverse events was significantly reduced by ETV plus Tα1, compared to ETV alone. Conclusions ETV plus Tα1 might lead to a higher clinical response and a lower comprehensive adverse reaction rate in HBV-related patients with cirrhosis, compared to ETV alone. However, the whole patients included in this meta-analysis were from Chinese mainland, so that more worldwide RCTs with a larger sample size are needed to verify the current findings.

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“…Thα1 is known as an effective therapeutic peptide for the treatment of some diseases . The major actions of this peptide are activation of cytokines, chemokines, and possessing antifungal as well as antibacterial effects .…”

Section: Discussionmentioning

confidence: 99%

Thymosin alpha‐1; a natural peptide inhibits cellular proliferation, cell migration, the level of reactive oxygen species and promotes the activity of antioxidant enzymes in human lung epithelial adenocarcinoma cell line (A549)

Kharazmi-Khorassani

Asoodeh

2019

Environmental Toxicology

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This research was conducted to investigate the biochemical effects of thymosin alpha-1 using human lung cancer cells (A549). The A549 cells were treated with different concentrations of Thα1 for 24 h and the growth, inhibition of cells was determined. Thα1 revealed anti-proliferative effect at 24 and 48 μg/ml after 24 h. Furthermore, it indicated antioxidant properties by significantly enhancing the activity of catalase (12 μg/ml), superoxide dismutase (6 and 12 μg/ml), and glutathione peroxidase (3, 6 and 12 μg/ml) and reducing the production of cellular ROS. Our results showed that Thα1 inhibits the migration of A549 cells in a concentration-dependent manner after 24 and 48 h. Moreover, the effect of Thα1 on apoptosis was investigated by Hoechst 33342 staining and cell cycle analysis. Results demonstrated no significant effect on the induction of apoptosis in A549 cells. In conclusion, our results showed the antioxidant properties of Thα1 on A549 cancer cells. K E Y W O R D S antioxidant enzyme, cytotoxicity, reactive oxygen species, thymosin alpha-1

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Immunotherapy for hepatitis B in the direct acting antiviral era: Reevaluating the thymosin α1 efficacy trials in the light of a combination therapy approach

Cited by 23 publications

References 37 publications

The Clinical Efficacy and Adverse Effects of Entecavir plus Thymosin alpha-1 Combination Therapy versus Entecavir Monotherapy in HBV-related Cirrhosis: A Systematic Review and Meta-analysis

The Clinical Efficacy and Adverse Effects of Entecavir plus Thymosin alpha-1 Combination Therapy versus Entecavir Monotherapy in HBV-related Cirrhosis: A Systematic Review and Meta-analysis

The Clinical Efficacy and Adverse Effects of Entecavir plus Thymosin alpha-1 Combination Therapy versus Entecavir Monotherapy in HBV-related Cirrhosis: A Systematic Review and Meta-analysis

Thymosin alpha‐1; a natural peptide inhibits cellular proliferation, cell migration, the level of reactive oxygen species and promotes the activity of antioxidant enzymes in human lung epithelial adenocarcinoma cell line (A549)

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