title: Soluble serum CD81 is elevated in patients with chronic hepatitis C and correlates with alanine aminotransferase serum activity.
abstract: OBJECTIVE
  Cellular CD81 is a well characterized hepatitis C virus (HCV) entry factor, while the relevance of soluble exosomal CD81 in HCV pathogenesis is poorly defined. We performed a case-control study to investigate whether soluble CD81 in the exosomal serum fraction is associated with HCV replication and inflammatory activity.
  
  
  METHODS
  Four cohorts were investigated, patients with chronic hepatitis C (n = 37), patients with chronic HCV infection and persistently normal ALT levels (n = 24), patients with long term sustained virologic response (SVR, n = 7), and healthy volunteers (n = 23). Concentration of soluble CD81 was assessed semi-quantitatively after differential centrifugation ranging from 200 g to 100,000 g in the fifth centrifugation fraction by immunoblotting and densitometry.
  
  
  RESULTS
  Soluble CD81 was increased in patients with chronic hepatitis C compared to healthy subjects (p = 0.03) and cured patients (p = 0.017). Patients with chronic HCV infection and persistently normal ALT levels and patients with long term SVR had similar soluble CD81 levels as healthy controls (p>0.2). Overall, soluble CD81 levels were associated with ALT levels (r = 0.334, p = 0.016) and severe liver fibrosis (p = 0.027).
  
  
  CONCLUSIONS
  CD81 is increased in the exosomal serum fraction in patients with chronic hepatitis C and appears to be associated with inflammatory activity and severity of fibrosis.
authors.affiliation: Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, Frankfurt am Main, Germany.
authors.forename: Martin-Walter
authors.initials: MW
authors.lastname: Welker
authors.forename: David
authors.initials: D
authors.lastname: Reichert
authors.forename: Simone
authors.initials: S
authors.lastname: Susser
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Martinez
authors.forename: Eva
authors.initials: E
authors.lastname: Herrmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Albrecht
authors.initials: A
authors.lastname: Piiper
authors.forename: Bernd
authors.initials: B
authors.lastname: Kronenberger
mesh_terms: D000410:Alanine Transaminase / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D055354:Exosomes / Q000235:genetics / Q000378:metabolism*; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000235:genetics / Q000821:virology; D006801:Humans; D015151:Immunoblotting; D012367:RNA, Viral / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D060225:Tetraspanin 28 / Q000097:blood*
chemical_list: D015415:Biomarkers; D012367:RNA, Viral; D060225:Tetraspanin 28; D000410:Alanine Transaminase