Clinical and Experimental Medicine

, Volume 19, Issue 3, pp 309–320 | Cite as

Changes in APRI and FIB-4 in HBeAg-negative treatment-naive chronic hepatitis B patients with significant liver histological lesions receiving 5-year entecavir therapy

  • Ruyu LiuEmail author
  • Jiang Guo
  • Yao Lu
  • Lu Zhang
  • Ge Shen
  • Shuling Wu
  • Mi Chang
  • Leiping Hu
  • Hongxiao Hao
  • Minghui Li
  • Yao Xie
Original Article


According to guidelines, antiviral therapy for adults with immune-active chronic hepatitis B (CHB) should be adopted to decrease the risk of liver-related complications. Fibrosis assessment during antiviral treatment is a key step in antiviral therapy evaluation. Liver biopsy is the gold standard for assessing the degree of liver necroinflammation and fibrosis. However, because of its cost and the risk of life-threatening complications, performing a liver biopsy more than once after long-term effective treatment is difficult. In this study, we aimed to evaluate changes in liver fibrosis during 5 years of entecavir (ETV) treatment using noninvasive fibrosis markers in hepatitis B e-antigen (HBeAg)-negative treatment-naive CHB patients who require antiviral therapy. A total of 303 HBeAg-negative treatment-naive patients were enrolled in this study. Liver biopsy was performed before initiation of antiviral therapy. The diagnosis of CHB was made according to Chinese guidelines for the management of CHB. Patients requiring antiviral therapy (liver fibrosis stage ≥ F2, METAVIR scoring system) were treated with ETV for at least 5 years. These patients were followed up at 6-month intervals. A clinical and virological evaluation was performed at baseline and again at 12, 24, 36, 48, and 60 months during ETV treatment. Aspartate Aminotransferase to Platelet Ratio Index (APRI) and Fibrosis-4 (FIB-4) index were used to assess dynamic changes in liver fibrosis in HBeAg-negative CHB patients after 1, 2, 3, 4, and 5 years of ETV treatment. All enrolled patients underwent liver biopsy at baseline. Using the METAVIR fibrosis stages, there were 107, 125, 54, and 17 patients in F1, F2, F3, and F4 stages, respectively. The APRI and FIB-4 indexes enabled the correct identification of patients with severe fibrosis (METAVIR F3–F4), with an area under the receiver operating characteristic curve of 0.77 (95% confidence interval [CI] 0.72–0.83) and 0.76 (95% CI 0.70–0.82), respectively. The APRI values decreased significantly in F2 and F3 patients after 1 year of ETV therapy (P < 0.01). However, for F4 patients, APRI values decreased significantly at year 3 (P < 0.05). The FIB-4 values of F2, F3, and F4 patients who received ETV treatment were significantly decreased after 1, 3, and 5 years of ETV therapy, respectively (P < 0.05). APRI and FIB-4 values decreased significantly during 5-year ETV treatment in HBeAg-negative CHB patients, indicating that these noninvasive fibrosis tests might be useful for monitoring improvement in liver fibrosis and assessing treatment efficacy during long-term ETV treatment.


Hepatitis B virus Chronic hepatitis B Liver fibrosis Entecavir APRI FIB-4 



This study was supported by Beijing Municipal Administration of Hospitals Incubating Program (PX2018060), Youth Programme from Beijing Municipal Administration of Hospitals (QML20181803), and Seedling Cultivation Programme of Beijing Ditan Hospital (DTYM201609).

Conflict of interest

The authors declare no competing financial interests.

Ethical approval and informed consent

All patients signed the informed consent before liver biopsy, and all clinical procedures were in accordance with the Declaration of Helsinki in 1983. The study protocol was permitted by the Institutional Review Board of Beijing Ditan Hospital.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Liver Diseases Center, Beijing Ditan HospitalCapital Medical UniversityBeijingPeople’s Republic of China
  2. 2.Tumor Interventional Department, Beijing Ditan HospitalCapital Medical UniversityChaoyang District, BeijingPeople’s Republic of China

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