title: Circulating microparticles as disease-specific biomarkers of severity of inflammation in patients with hepatitis C or nonalcoholic steatohepatitis.
abstract: OBJECTIVE
  Microparticles released into the bloodstream upon activation or apoptosis of CD4(+) and CD8(+) T cells correlate with inflammation as determined by histologic analysis in patients with chronic hepatitis C (CHC). Patients with nonalcoholic fatty liver (NAFL) or nonalcoholic steatohepatitis (NASH) can be differentiated from those with CHC based on activation of distinct sets of immune cells in the liver.
  
  
  METHODS
  We compared profiles of circulating microparticles from patients with NAFL and NASH (n = 67) to those of CHC (n = 42), with healthy individuals (controls) using flow cytometry; the profiles were correlated with inflammation grade and fibrosis stage based on histologic analyses. We assessed the ability of the profiles to determine the severity of inflammation and fibrosis based on serologic and histologic analyses.
  
  
  RESULTS
  Patients with CHC had increased levels of microparticles from CD4(+) and CD8(+) T cells; the levels correlated with disease severity based on histologic analysis and levels of alanine aminotransferase. Patients with NAFL or NASH had significant increases in numbers of microparticles from invariant natural killer T cells and macrophages/monocytes (CD14(+)), which mediate pathogenesis of NASH. Microparticles from CD14(+) and invariant natural killer T cells correlated with levels of alanine aminotransferase and severity of NASH (based on histology). Levels of microparticles could differentiate between patients with NAFL or NASH and those with CHC, or either group of patients and controls (area under the receiver operating characteristic curves ranging from 0.56 to 0.99).
  
  
  CONCLUSIONS
  Quantification of immune cell microparticles from serum samples can be used to assess the extent and characteristics of hepatic inflammation in patients with chronic liver disease.
authors.affiliation: Harvard Medical School, Boston, MA, USA.
authors.forename: Miroslaw
authors.initials: M
authors.lastname: Kornek
authors.forename: Michael
authors.initials: M
authors.lastname: Lynch
authors.forename: Shruti H
authors.initials: SH
authors.lastname: Mehta
authors.forename: Michelle
authors.initials: M
authors.lastname: Lai
authors.forename: Mark
authors.initials: M
authors.lastname: Exley
authors.forename: Nezam H
authors.initials: NH
authors.lastname: Afdhal
authors.forename: Detlef
authors.initials: D
authors.lastname: Schuppan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001707:Biopsy, Needle; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D003937:Diagnosis, Differential; D005234:Fatty Liver / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D005260:Female; D005434:Flow Cytometry; D019698:Hepatitis C, Chronic / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology*; D016014:Linear Models; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D012372:ROC Curve; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D000410:Alanine Transaminase