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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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.
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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).
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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