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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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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.


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.


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.


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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Chronic hepatitis B


Tenofovir disoproxil fumarate


Second harmonic generation


Two-photon excitation fluorescence


Human immunodeficiency virus


Hematoxylin and eosin


Histology Activity Index

P-I-R :

Predominantly progressive, indeterminate, and predominately regressive


Collagen proportionate area


International normalized ratio




Liver stiffness measurement


Body mass index


Interquartile range


Standard deviation


Alanine aminotransferase


Aspartate aminotransferase






Total bilirubin


Fibrosis-4 score


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


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

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Authors and Affiliations



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.

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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).

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