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Comparison of fibrosis regression of entecavir alone or combined with pegylated interferon alpha2a in patients with chronic hepatitis B

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Abstract

Background and aims

Antiviral treatment with necleos(t)ide analogues contributes to histological improvement and virologic response in chronic hepatitis B (CHB) patients. However, whether adding pegylated interferon alpha2a (Peg-IFN-α-2a) can help additional clinical benefit, particularly on fibrosis regression was still unknown.

Methods

Chronic hepatitis B patients with pre-treatment biopsy-proven Ishak fibrosis score 2, 3 or 4 were randomly assigned to entecavir (ETV) alone or ETV plus Peg-IFN-α-2a (Peg-IFN-α-2a add-on) group (1:2 ratio). Post-treatment liver biopsy was performed at week 78. Fibrosis regression was defined as decrease in Ishak fibrosis score by ≥ 1 stage or predominantly regressive categorized by P–I–R score. Serum HBV DNA levels were assessed at baseline and every 26 weeks, while HBsAg and HBeAg were evaluated at baseline and every 52 weeks.

Results

A total of 218 treatment-naive CHB patients were randomly assigned to ETV alone or Peg-IFN-α-2a add-on group. Totals of 155 patients (ETV alone: Peg-IFN-α-2a add-on, 47:108) were included in statistical analysis. Fibrosis regression rates were 68% (32/47) in the ETV alone and 56% (60/108) in Peg-IFN-α-2a add-on group (p = 0.144). Both groups showed a similar trend of virological suppression during the process of 104-week antiviral therapy (p = 0.132). HBeAg or HBsAg loss or seroconversion rates in the ETV alone group were lower than Peg-IFN-α-2a add-on group though without statistical significance.

Conclusions

Peg-IFN-α-2a add-on therapy did not yield additional fibrosis regression and virologic response than ETV alone therapy.

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Abbreviations

CHB:

Chronic hepatitis B

Peg-IFN-α-2a:

Pegylated interferon alpha2a

ETV:

Entecavir

P-I-R:

Predominantly progressive, indeterminate and predominately regressive

HBV:

Hepatitis B virus

HBsAg:

Hepatitis B surface antigen

HBeAg:

Hepatitis B e antigen

NAs:

Necleos(t)ide analogues

IFNa:

Interferon-alpha

AFP:

Alpha fetoprotein

ULN:

Upper limit of normal

AE:

Adverse event

SAE:

Serious adverse event

H & E:

Hematoxylin and eosin

HAI:

Histology activity index

LSM:

Liver stiffness measurement

APRI:

Aminotransferase-to-platelet ratio index

FIB-4:

Fibrosis-4 score

IQR:

Interquartile range

SD:

Standard deviation

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

PLT:

Platelet

BMI:

Body mass index

WBC:

White blood cell count

ALB:

Albumin

TB:

Total bilirubin

INR:

International normalized ratio

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Funding

This study was funded by the National Science and Technology Major Project (2018ZX10302204, 2018ZX10302204-004) and the National Natural Science Foundation of China (81800535 and 81670539).

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Author notes

  1. Shuyan Chen and Jialing Zhou contributed equally to this paper.

Authors and Affiliations

  1. Liver Research Center, Beijing Key Laboratory of Translational Medicine On Liver Cirrhosis, Beijing Friendship Hospital, National Clinical Research Center of Digestive Diseases, Capital Medical University, 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, China

    Shuyan Chen, Jialing Zhou, Xiaoning Wu, Tongtong Meng, Bingqiong Wang, Xinyan Zhao, Yuanyuan Kong, Shanshan Wu, Xiaojuan Ou, Jidong Jia, Yameng Sun & Hong You

  2. Department of Pathology, Beijing You-an Hospital, Capital Medical University, Beijing, China

    Hui Liu

  3. Department of Pathology, China-Japan Friendship Hospital, Beijing, China

    Tailing Wang

Authors
  1. Shuyan Chen
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Contributions

Study design: HY and JDJ. Liver biopsy assessment: TLW, HL, YMS, XYZ. Data collection: JLZ, YMS, XNW, TTM, XJO, BQW, SYC. Statistical analysis: SYC, YYK, SSW. Manuscript writing: SYC, JLZ. Critical revision of the manuscript: HY, YMS.

Corresponding authors

Correspondence to Yameng Sun or Hong You.

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Conflicts of interest

All authors have nothing to disclose.

Ethical approval

The study was conducted in accordance with the principles enshrined in the Declaration of Helsinki and the Good Clinical Practices. The Ethics Committee of all participating centers approved the study protocol (2016-P2-021-02).

Informed consent

All patients gave written informed consent prior to their enrollment.

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All authors had access to the study data and reviewed and approved the final manuscript.

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Chen, S., Zhou, J., Wu, X. et al. Comparison of fibrosis regression of entecavir alone or combined with pegylated interferon alpha2a in patients with chronic hepatitis B. Hepatol Int 15, 611–620 (2021). https://doi.org/10.1007/s12072-021-10162-1

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  • DOI: https://doi.org/10.1007/s12072-021-10162-1

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