title: Hyaluronic acid levels predict risk of hepatic encephalopathy and liver-related death in HIV/viral hepatitis coinfected patients.
abstract: BACKGROUND
  Whereas it is well established that various soluble biomarkers can predict level of liver fibrosis, their ability to predict liver-related clinical outcomes is less clearly established, in particular among HIV/viral hepatitis co-infected persons. We investigated plasma hyaluronic acid's (HA) ability to predict risk of liver-related events (LRE; hepatic coma or liver-related death) in the EuroSIDA study.
  
  
  METHODS
  Patients included were positive for anti-HCV and/or HBsAg with at least one available plasma sample. The earliest collected plasma sample was tested for HA (normal range 0-75 ng/mL) and levels were associated with risk of LRE. Change in HA per year of follow-up was estimated after measuring HA levels in latest sample before the LRE for those experiencing this outcome (cases) and in a random selection of one sixth of the remaining patients (controls).
  
  
  RESULTS
  During a median of 8.2 years of follow-up, 84/1252 (6.7%) patients developed a LRE. Baseline median (IQR) HA in those without and with a LRE was 31.8 (17.2-62.6) and 221.6 ng/mL (74.9-611.3), respectively (p<0.0001). After adjustment, HA levels predicted risk of contracting a LRE; incidence rate ratios for HA levels 75-250 or ≥250 vs. <75 ng/mL were 5.22 (95% CI 2.86-9.26, p<0.0007) and 28.22 (95% CI 14.95-46.00, p<0.0001), respectively. Median HA levels increased substantially prior to developing a LRE (107.6 ng/mL, IQR 0.8 to 251.1), but remained stable for controls (1.0 ng/mL, IQR -5.1 to 8.2), (p<0.0001 comparing cases and controls), and greater increases predicted risk of a LRE in adjusted models (p<0.001).
  
  
  CONCLUSIONS
  An elevated level of plasma HA, particularly if the level further increases over time, substantially increases the risk of contracting LRE over the next five years. HA is an inexpensive, standardized and non-invasive supplement to other methods aimed at identifying HIV/viral hepatitis co-infected patients at risk of hepatic complications.
authors.affiliation: Copenhagen HIV Programme, University of Copenhagen, Copenhagen, Denmark. lpe@cphiv.dk
authors.forename: Lars
authors.initials: L
authors.lastname: Peters
authors.forename: Amanda
authors.initials: A
authors.lastname: Mocroft
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
authors.forename: Jürgen
authors.initials: J
authors.lastname: Rockstroh
authors.forename: Andri
authors.initials: A
authors.lastname: Rauch
authors.forename: Anders
authors.initials: A
authors.lastname: Karlsson
authors.forename: Brygida
authors.initials: B
authors.lastname: Knysz
authors.forename: Christian
authors.initials: C
authors.lastname: Pradier
authors.forename: Kai
authors.initials: K
authors.lastname: Zilmer
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D060085:Coinfection / Q000097:blood* / Q000150:complications*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000097:blood*; D006501:Hepatic Encephalopathy / Q000097:blood* / Q000150:complications* / Q000401:mortality; D006525:Hepatitis, Viral, Human / Q000097:blood*; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D018570:Risk Assessment; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006820:Hyaluronic Acid