Association of apolipoprotein E with the progression of hepatitis B virus-related liver disease

Int J Clin Exp Pathol. 2015 Nov 1;8(11):14749-56. eCollection 2015.


Hepatitis B virus (HBV) infection increases the risk of liver decompensation, cirrhosis and hepatocellular carcinoma (HCC). Apolipoprotein E (ApoE), one of the major cholesterol carriers, plays important role in the metabolism of lipoprotein and the regulation of immune response. The present study was aimed to explore whether the genetic variation in ApoE gene affected disease progression in HBV infected individuals. We collected sera samples from healthy volunteers (n=40), inactive HBV carriers (n=30), and patients with acute hepatitis (n=60), severe hepatitis (n=12), HBV-related liver cirrhosis (n=58) or primary HCC (n=39). We found that ApoE and interlukin-6 (IL-6) was progressively increased, while IL-2 was gradually decreased with the increasing grade of disease severity. Furthermore, high ApoE levels in HBV infected individuals were correlated with increased IL-6 and decreased IL-2 levels, indicating immune abnormalities in these patients. The frequency of E3/3 genotype was progressively increased from carriers group, hepatitis group to progressive group (cirrhosis and HCC). The serum levels of low-density lipoprotein cholesterol (LDL-C) differed among ApoE phenotypes, with E3/4, E4/4> E3/3>E2/3. Our study suggested that ApoE may have a role in the pathogenesis and progression of HBV-related liver disease and indicated the possible underlying mechanisms.

Keywords: Hepatitis B virus; apolipoprotein E; polymorphisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Apolipoproteins E / genetics*
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Hepatitis B / complications*
  • Hepatitis B / genetics
  • Humans
  • Liver Diseases / genetics*
  • Liver Diseases / virology*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Reverse Transcriptase Polymerase Chain Reaction


  • Apolipoproteins E