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Safety and efficacy of Thymosin α1 in the treatment of hepatitis B virus-related acute-on-chronic liver failure: a randomized controlled trial

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Abstract

Background/purpose of the study

Mortality from hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) is high. Severe infection is the most important complication that affects the outcomes of ACLF patients. Thymosin α1 (Tα1) can improve immune imbalance and this study aimed to investigate the safety and efficacy of Tα1 treatment for HBV-related ACLF.

Methods

From 2017 to 2019, 120 patients with HBV-related ACLF were enrolled in this open-label, randomized, and controlled clinical trial (ClinicalTrial ID: NCT 03082885). The control group (N = 58) was treated with standard medical therapy (SMT) only. The experimental group (N = 56) was subcutaneously injected with 1.6 mg of Tα1 once a day for the first week and then twice a week from week 2 to week 12.

Results

The 90-day cumulated liver transplantation free survival rate of the Tα1 group was 75.0% (95% confidence interval 63.2–86.8%) versus 53.4% (95% confidence interval 39.7–67.1%) for the SMT group (p = 0.030). No significant difference was found in the survival using competitive risk analysis. The incidences of new infection and hepatic encephalopathy in the Tα1 group were much lower than those in the SMT group (32.1% vs 58.6%, p = 0.005; 8.9% vs 24.1%, p = 0.029, respectively). Mortality from severe infection in the SMT group was higher than in the Tα1 group (24.1% vs 8.9%, p = 0.029).

Conclusion

Tα1 is safe for patients with HBV-related ACLF and significantly improves the 90-day liver transplantation-free survival rate. There may be a subgroup which may benefit from Tα1 therapy by the mechanism of preventing infection.

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Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

ACLF:

Acute-on-chronic liver failure

ALB:

Albumin

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

CI:

Confidence interval

CLIF-C OF:

Chronic liver failure consortium organ failure

CLIF-SOFA:

Chronic liver failure consortium sequential organ failure assessment

CRP:

C-reactive protein

CTL:

Cytotoxic T cells

Cr:

Creatinine

CT:

Computed tomography

DCs:

Dendritic cells

ESR:

Red blood cell sedimentation rate

HBV:

Hepatitis B virus

HR:

Hazard ratio

Th:

Helper T

INR:

International normalized ratio

ITT:

Intent-to-treat

MELD:

Model for end-stage liver disease

MAPK:

Mitogen-activated protein kinases

MRI:

Magnetic resonance imaging

NK:

Natural killer

NF-κB:

Nuclear factor-κ-gene binding

NNT:

Number needed to treat

PCT:

Procalcitonin

PTA:

Prothrombin activity

SAE:

Serious adverse events

SMT:

Standard medical therapy

TB:

Total bilirubin

Tα1:

Thymosin α1

TLR:

Toll-like receptor

WBCs:

White blood cells

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Acknowledgements

We thank all the patients participated in this research. We thank Professor Jian-rong He (Guangzhou Women and Children’s Medical Center) for directing us in data statistics. We thank Yu-xin Yang and Jin-xiu Cao for help in proofreading the manuscript.

Funding

This research was supported by the following funding sources: National Natural Science Foundation of China (82070612, 81901940); National Science and Technology Major Project of China(2018ZX10302204, 2017ZX10203201003); Natural Science Foundation of Guangdong Province (2021A1515010306); The Guangzhou Major Project in collaborative innovation of industry (1561000157).

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Author notes

  1. Jun-feng Chen and Shu-ru Chen contributed equally to this work.

Authors and Affiliations

  1. Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Tianhe Area, Guangzhou, 510630, China

    Jun-feng Chen, Shu-ru Chen, Zi-ying Lei, Hui-juan Cao, Shao-quan Zhang, Wei-zhen Weng, Jing Xiong, Deng-na Lin, Jing Zhang, Yu-bao Zheng, Zhi-liang Gao & Bing-liang Lin

  2. Guangdong Provincial Key Laboratory of Liver Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China

    Zhi-liang Gao & Bing-liang Lin

  3. Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, 510080, Guangdong, China

    Zhi-liang Gao & Bing-liang Lin

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  1. Jun-feng Chen
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Contributions

B-lL, J-fC, S-rC, Z-yL, H-jC, S-qZ, W-zW, JX, D-nL, JZ and Y-bZ performed clinical study; B-lL and Z-lG provided financial support for this work; B-lL designed the study; J-fC and B-lL performed the analysis and interpretation of the data; J-fC and B-lL wrote and edited the manuscript. The corresponding authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Corresponding author

Correspondence to Bing-liang Lin.

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Conflict of interest

In this study, Sciclone pharmaceuticals, as the Marketing Authorization Holder of Tα-1 in China, reported SAEs to the drug and regulatory and health authorities after being informed by investigators. Sciclone did not play any role in the design, conduct or funding of this study. The authors have no conflict of interest to declare.

Ethical approval

This study conformed strictly to the Ethical Guidelines of the 1975 Declaration of Helsinki. The study protocol was approved by the Ethics Committee on Clinical Trials of the Third Affiliated Hospital of Sun Yat-sen University in 2016. This study is registered at ClinicalTrials.gov (NCT 03082885). Informed consent was obtained from all patients for being included in the study.

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Consent for publication was obtained from all co-authors.

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Chen, Jf., Chen, Sr., Lei, Zy. et al. Safety and efficacy of Thymosin α1 in the treatment of hepatitis B virus-related acute-on-chronic liver failure: a randomized controlled trial. Hepatol Int 16, 775–788 (2022). https://doi.org/10.1007/s12072-022-10335-6

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  • DOI: https://doi.org/10.1007/s12072-022-10335-6

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