Relationship between level of hepatitis B virus DNA and liver disease: a population-based study of hepatitis B e antigen-negative persons with hepatitis B

Clin Gastroenterol Hepatol. 2014 Apr;12(4):701-6.e1-3. doi: 10.1016/j.cgh.2013.09.005. Epub 2013 Sep 11.

Abstract

Background & aims: There is little information on the proportion of persons with chronic hepatitis B virus (HBV) infection with active hepatitis. We aimed to determine the proportion of persons with hepatitis B e antigen-negative chronic HBV infection who develop immune-active HBV infection over time and the relationship between demographic and viral factors on severity of disease on liver biopsy.

Methods: We performed a longitudinal population-based cohort study of 754 Alaska Native patients with chronic HBV infection. Levels of alanine aminotransferase (ALT) were measured every 6 months, and levels of HBV DNA were measured at study entry and whenever ALT levels exceeded the upper limit of normal (ULN). Immune-active chronic HBV infection was defined as levels of ALT ≥ 30 U/L in men and >20 U/L in women and levels of HBV DNA >2000 IU/mL at 1 or more time points from 2001-2008. Liver biopsies were scored by using the modified histology activity index score of Knodell and the Ishak fibrosis score.

Results: Of the study participants, 186 (25%) met the criteria for immune-active HBV, 56% of these initially and 44% later during follow up. Of the 38 patients with liver biopsy results, only 1 of 16 with ALT levels consistently below twice the ULN and 1 of 19 with HBV DNA between 2000 and 20,000 IU/mL, vs 12 of 22 (55%) with ALT > twice ULN (P = .002) and 11 of 18 (61%) with 1 or more measurements of HBV DNA >20,000 IU/mL (P < .001), had moderate or severe hepatitis or fibrosis.

Conclusions: In a cohort of Alaska Natives with chronic HBV infection, 25% met criteria for immune-active HBV. There is a low probability of advanced fibrosis if levels of HBV DNA never exceed 20,000 IU/mL.

Keywords: HBV Genotype; HBsAg; Liver Biopsy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine Transaminase / blood
  • Alaska
  • Biopsy
  • Cohort Studies
  • DNA, Viral / blood
  • Female
  • Hepatitis B Antigens / blood*
  • Hepatitis B virus / isolation & purification*
  • Hepatitis B, Chronic / pathology*
  • Hepatitis B, Chronic / virology*
  • Histocytochemistry
  • Humans
  • Liver Cirrhosis / pathology*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Viral Load*

Substances

  • DNA, Viral
  • Hepatitis B Antigens
  • Alanine Transaminase