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Liver fibrosis showed a two-phase regression rate during long-term anti-HBV therapy by three-time biopsies assessments

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Abstract

Background

Evidence has proven that liver fibrosis or even cirrhosis can be reversed by anti-HBV treatment. However, the difference of fibrosis regression rates in short-term and long-term antiviral therapy remain unclear. Therefore, we aimed to identify the dynamic changes in fibrosis regression rate in patients with three-time liver biopsies during 5 years antiviral therapy.

Methods

CHB patients with three times of liver biopsies (baseline, after 1.5-year and 5-year antiviral therapy) from a prospective cohort were enrolled. All patients were biopsy-proved Ishak stage ≥ 3 at baseline (n = 92). Fibrosis regression was defined as Ishak stage decreased ≥ 1 or predominantly regressive categorized by P-I-R score.

Results

Totals of 65.2% (60/92) and 80.4% (74/92) patients attained fibrosis regression after 1.5-year and 5-year therapy, respectively. Median HBV DNA level declined from 6.5 log IU/ml (baseline) to 0 log IU/ml (1.5 years and 5 years, P < 0.001). The mean level of Ishak fibrosis stage in all patients decreased from stage 4.1 (baseline) to 3.7 (1.5 years) then 3.2 (5 years). Fibrosis regression rates were 0.27 stage/year between baseline to year 1.5 and 0.14 stage/year between year 1.5 and year 5. Furthermore, for patients who attained fibrosis regression after 5-year antiviral therapy, the two-phase regression rates were 0.39 stage/year (0 year–1.5 years) and 0.20 stage/year (1.5 years–5 years). This two-phase feature of regression rate was further confirmed by fully-quantification assessment of liver fibrosis based on SHG/TPEF.

Conclusion

During the 5 years of long-term antiviral treatment, liver fibrosis rapidly regresses in the first 1.5 years before slowing down in the following 3.5 years.

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Data availability

No additional data are available.

Abbreviations

CHB:

Chronic hepatitis B

TDF:

Tenofovir disoproxil fumarate

SHG:

Second harmonic generation

TPEF:

Two-photon excitation fluorescence

HIV:

Human immunodeficiency virus

H&E:

Hematoxylin and eosin

HAI:

Histology Activity Index

P-I-R :

Predominantly progressive, indeterminate, and predominately regressive

CPA:

Collagen proportionate area

INR:

International normalized ratio

AFP:

Alpha-fetoprotein

LSM:

Liver stiffness measurement

BMI:

Body mass index

IQR:

Interquartile range

SD:

Standard deviation

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

PLT:

Platelet

ALB:

Albumin

TB:

Total bilirubin

Fib-4:

Fibrosis-4 score

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Acknowledgements

The authors acknowledge the patients and study investigators for their contributions in this study.

Funding

This study was funded by National Science and Technology Major Project (2018ZX10302204, 2017ZX10203202-003) and Beijing Municipal Science & Technology Commission (Z221100007422115).

Author information

Author notes

  1. Yameng Sun and Hong You share co-corresponding authorship.

Authors and Affiliations

  1. Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, Beijing, China

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

  2. Department of Pathology, Beijing Youan Hospital, Capital Medical University, Beijing, China

    Hui Liu

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

    Tailing Wang

  4. Clinical Epidemiology and EBM Unit, Beijing Friendship Hospital, Capital Medical University, Beijing Clinical Research Institute, Beijing, China

    Xinyu Zhao & Yuanyuan Kong

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  1. Shuyan Chen
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Contributions

HY and JDJ designed the study. TLW, HL, YMS and XYZ assessed the liver biopsy. JLZ, YMS, SYC, XNW, TTM, BQW and XJO collected the data. SYC, YYK and XYZ analyzed the data. SYC writed the manuscript. YMS and HY revised the manuscript.

Corresponding authors

Correspondence to Yameng Sun or Hong You.

Ethics declarations

Conflict of interest

Shuyan Chen, Jialing Zhou, Xiaoning Wu, Tongtong Meng, Bingqiong Wang, Hui Liu, Tailing Wang, Xinyan Zhao, Xinyu Zhao, Yuanyuan Kong, Xiaojuan Ou, Jidong Jia, Yameng Sun, Hong You have no relevant financial or non-financial interests to disclose.

Ethical approval

Our study was conducted according to the principles enshrined in the Declaration of Helsinki and the Good Clinical Practices. The Ethics Committee of all participating centers approved the study protocol (2018-P2-106-04, 2016-P2-021-04). All patients provided written informed consent before 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. Liver fibrosis showed a two-phase regression rate during long-term anti-HBV therapy by three-time biopsies assessments. Hepatol Int 18, 904–916 (2024). https://doi.org/10.1007/s12072-024-10643-z

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  • DOI: https://doi.org/10.1007/s12072-024-10643-z

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