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High-risk population of progressive hepatic fibrosis in chronic hepatitis B patients on antiviral therapy

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

Progressive hepatic fibrosis leads to hepatocellular carcinoma (HCC) and decompensated cirrhosis. The aim of this study was to identify the high-risk population for progressive hepatic fibrosis and the incidence of HCC and decompensated cirrhosis in chronic hepatitis B (CHB) patients with antiviral therapy.

Methods

The data came from a multicenter, center-randomized, double-blind clinical trial that analyzed only patients in the ETV-treated arm. There was 156 hepatitis B e antigen (HBeAg)-positive and 135 HBeAg-negative patients in 14 institutions. The primary endpoint was fibrosis reversal on 72-week Entecavir (ETV) treatment. The 7-year cumulative incidence of HCC and decompensated cirrhosis were analyzed. Multivariate logistic and LASSO regression analyses were used to screen variables associated with fibrosis reversal.

Results

86/156 (55%) HBeAg-positive and 58/135 (43%) HBeAg-negative patients achieved fibrosis reversal on 72-week ETV treatment. Average age was 43 years, 203 (69.8%) was male, and 144 (49.5%) patients had cirrhosis. Age ≥ 40 years (OR: 0.46, 95% CI 0.23–0.93) and HBcrAg ≥ 8.23 log U/ml (OR: 2.72, 95% CI 1.33–5.54) in HBeAg-positive patients and HBV genotype C (OR: 0.44, 95% CI 0.21–0.97) in HBeAg-negative patients were independent factors of fibrosis reversal. It was confirmed in patients with cirrhosis. After 7-year ETV treatment, seven (4.5%) HBeAg-positive patients occurred HCC or decompensated cirrhosis, including four patients with age ≥ 40 years and six with HBcrAg 8.23log U/ml, while twelve (8.9%) HBeAg-negative patients occurred, including eleven with HBV genotype C.

Conclusions

HBeAg-positive patients with a low HBcrAg level or old age, and HBeAg-negative patients with HBV genotype C tended to develop progressive hepatic fibrosis and had a high incidence of HCC and decompensated cirrhosis, even on ETV treatment.

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Acknowledgements

We appreciate the Major Science and Technology Special Project of China (2018ZX10725-506) and Beijing Natural Science Foundation (7212101) for funding support. We are very grateful to professor Jingfeng Bi, a statistician, for the statistical guidance.

Author information

Author notes

  1. Xiujuan Chang, Yinying Li, Chao Sun, and Xiaodong Li contributed equally to this work.

Authors and Affiliations

  1. Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China

    Xiujuan Chang, Yinying Li & Yongping Yang

  2. Chinese PLA Medical School, Beijing, 100853, China

    Chao Sun & Yongping Yang

  3. Department of Research for Clinical Medicine, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China

    Xiaodong Li

  4. Discipline and Degree Division, the Graduate School of the PLA General Hospital, Beijing, 100853, China

    Wenjuan Du

  5. Center of Therapeutic Liver Disease, the 88th Hospital of Chinese PLA, Taian, 271000, Shandong Province, China

    Qinghua Shang

  6. Traditional Chinese Medicine Hospital of Taihe, Taihe, 400038, Anhui Province, China

    Laicheng Song

  7. Department of Infection and Liver Disease, Yichun People’s Hospital, Yichun, Jiangxi Province, China

    Qinghua Long

  8. Fuzhou Infectious Diseases Hospital, Fuzhou, 350025, Fujian Province, China

    Qin Li

  9. Traditional Chinese Medicine Hospital of Chongqing, Chongqing, 400038, China

    Huabao Liu

  10. Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 610072, Sichuan Province, China

    Jing Wang

  11. Department of Infectious Disease, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China

    Zujiang Yu

  12. Department of Infectious Diseases, Southwest Hospital, Army Military Medical University, Chongqing, 400038, China

    Jiang Li

  13. Guangzhou 8th People’s Hospital, Guangzhou, 510060, Guangdong Province, China

    Guangming Xiao

  14. Department of Traditional Chinese Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China

    Li Li

  15. Department of Hepatic Diseases, Shanghai Public Health Clinical Center, Shanghai, 201508, China

    Liang Chen

  16. Department of Liver Disease, Fuyang 2nd People’s Hospital, Fuyang, 236015, Anhui Province, China

    Lin Tan

  17. Department of Infectious and Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China

    Yongping Chen

Authors
  1. Xiujuan Chang
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  2. Yinying Li
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Contributions

All authors approved the final version of the manuscript. YY and XC had full access to all data in the study and assume responsibility for the integrity of the data and accuracy of the data analysis. YY conceptualized and designed the study. XL and CS helped with the acquisition, analysis, and interpretation of data. XC, XL, and WD drafted the manuscript. All authors critically revised the manuscript for important intellectual content. XC helped with statistical analysis. YY obtained funding. YL, QS, LS, QL, QL, HL, JW, ZY, JL, GX, LL, LC, LT, and YC provided administrative, technical, and material support. YY supervised the study.

Corresponding authors

Correspondence to Yongping Chen or Yongping Yang.

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Chang, X., Li, Y., Sun, C. et al. High-risk population of progressive hepatic fibrosis in chronic hepatitis B patients on antiviral therapy. J Gastroenterol 58, 481–493 (2023). https://doi.org/10.1007/s00535-023-01970-3

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  • DOI: https://doi.org/10.1007/s00535-023-01970-3

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