Combination of entecavir with thymosin alpha-1 in HBV-related compensated cirrhosis: a prospective multicenter randomized open-label study

 ABSTRACT

Background: Thymosin alpha-1 (Ta-1) suppresses HBV viral replication, while the evidence of combination effect with nucleoide is still limited. We aimed to investigate the efficacy and safety of combination therapy of Ta-1 with entecavir (ETV) in patients with compensated liver cirrhosis.

Research design and methods: A total of 690 patients were randomized to receive Ta-1 plus ETV (n = 351) or ETV monotherapy (n = 339) for 52 weeks after 26 weeks of ETV treatment, followed by continued entecavir therapy. The primary endpoint was defined as liver decompensation, hepatocellular carcinoma (HCC) or death.

Results: The median followed up was 38.2 months. The cumulative incidence of liver decompensation, HCC, or death were similar between two groups. During the Ta-1 combination treatment, the HCC incidence was 1.7% in combination group and 2.1% in ETV group, without new HCC cases developed during week 39 to week 77 in combination group. The virologic response, serologic response, biochemical response was similar between two groups at week 104. Both therapies were well-tolerated.

Conclusion: There was no significant difference between two groups in endpoint events, while combination therapy with Ta-1 has a tendency to inhibit the development of HCC.

KEYWORDS:

• Hepatitis B virus
• liver cirrhosis
• hepatocellular carcinoma
• immune regulator
• thymosin alpha-1/Ta-1

Acknowledgements

This study was supported by The National Science and Technology Major Project (2013ZX10002004), Project of Beijing Municipal Science and Technology Commission (D121100003912003, Z151100004015237) and National Key Technologies R&D Program (2015BAI13B09). This paper has been published as part of a supplement issue covering the proceedings of the Fifth International Symposium on Thymosins in Health and Disease and is funded by SciClone Pharmaceuticals.

Author contributions

Xiaoning Wu and Yiwen Shi contributed equally to this work. Study concept and design: Hong You, Jidong Jia, Xiaojuan Ou, Hong Ma. Acquisition of data: Xiaoning Wu, Yameng Sun, Jialing Zhou, Bingqiong Wang, Shuyan Chen, Yiwen Shi, Xiaojuan Ou, Hong Ma, Hongxin Piao, Wei Jiang, Anlin Ma, Yongpeng Chen, Mingyi Xu, Wen Xie, Jun Cheng, Shibin Xie, Jia Shang, Jilin Cheng, Qing Xie, Huiguo Ding, Xuqing Zhang, Lang Bai, Mingxiang Zhang. Analysis and interpretation of data: Yiwen Shi, Xiaoning Wu, Yameng Sun, Jialing Zhou. Literature research: Xiaoning Wu, Yiwen Shi. Statistical analysis: Xiaoning Wu, Yiwen Shi. Drafting of the manuscript: Xiaoning Wu, Yiwen Shi, Hong You. Guarantor of integrity of entire study: Hong You. Critical revision of manuscript: Hong You. Manuscript final version approval: All the authors.

Declaration of interest

The authors declared that the Ta-1 in this study was provided by SciClone Pharmaceuticals International China Holding Ltd. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This study was supported by The National Science and Technology Major Project (2013ZX10002004), Project of Beijing Municipal Science and Technology Commission (D121100003912003, Z151100004015237) and National Key Technologies R&D Program (2015BAI13B09). This paper has been published as part of a supplement issue covering the proceedings of the Fifth International Symposium on Thymosins in Health and Disease and is funded by SciClone Pharmaceuticals.