Clinical and histopathological features of chronic hepatitis B virus infected patients with high HBV-DNA viral load and normal alanine aminotransferase level: A multicentre-based study in China

PLoS One. 2018 Sep 4;13(9):e0203220. doi: 10.1371/journal.pone.0203220. eCollection 2018.

Abstract

Background: The aim of this study is to reveal the clinical and histopathological features of HBsAg-positive and HBeAg-positive chronic hepatitis B infected patients with high level of HBV DNA, from 17 hospitals and medical centres in China, with alanine aminotransferase levels within the lower region of normal range versus those with levels within the upper region of normal range and to investigate the clinical risk factors for the requirement of treatment through the examination of liver biopsy.

Methods: Liver biopsy was performed on high level of HBV DNA of 455 patients with HBsAg-positive and HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase level. Liver necroinflammation and fibrosis were graded per the Knodell histological activity index and Ishak's fibrosis score, respectively. Univariate analysis of the clinical parameters versus necroinflammation and fibrosis was carried out.

Results: Of the subjects in this multicentre-based study, 5.49% and 10.11% had significant necroinflammation with Knodell histological activity index ≥ 9 and hepatic fibrosis stages with Ishak scores ≥ 3, respectively. The subjects were stratified into three age groups (30-39, 40-49 and ≥ 50 years), and our data clearly suggested that age, particularly in the age group over 50, was an independent predictor of liver necroinflammation and fibrosis. Lower HBV-DNA viral levels were found in patients with Knodell histological activity index ≥ 9 or advanced fibrosis (Ishak scores ≥ 3).

Conclusion: Our results showed that histological changes in liver tissues were observed in a significant proportion of patients with persistently normal alanine aminotransferase level. According to the data evaluation results, liver biopsy is advisable for HBeAg-positive chronic hepatitis B infected patients aged older than 40 and high HBV-DNA viral load in China.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine Transaminase / blood*
  • Biopsy
  • China
  • DNA, Viral / blood*
  • DNA, Viral / genetics
  • Female
  • Hepatitis B e Antigens / blood
  • Hepatitis B virus / genetics
  • Hepatitis B, Chronic / enzymology*
  • Hepatitis B, Chronic / pathology
  • Hepatitis B, Chronic / virology*
  • Humans
  • Liver / pathology
  • Liver Cirrhosis / pathology
  • Male
  • Middle Aged
  • Viral Load

Substances

  • DNA, Viral
  • Hepatitis B e Antigens
  • Alanine Transaminase

Grants and funding

This study was supported by the National Science and Technology Major Project (2008ZX10005008; 2012ZX10005006 to GDT) and Guangdong Province Science and Technology Project (2017A020213016 to YFX) and Shenzhen Basic Research Program (JCYJ20160229173844278 to COC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.