title: Worsening of hepatic dysfunction as a consequence of repeated hydroxyethylstarch infusions.
abstract: OBJECTIVE
  Due to its apparent safety and low cost, hydroxyethylstarch (HES) is increasingly used as a volume expander. The aim of this retrospective study was to highlight the risk of hepatic dysfunction after iterative HES infusions.
  
  
  METHODS
  Between April 1996 and April 1998, nine patients were referred for worsening of their clinical condition after repeated HES infusions. Six patients had previous chronic liver disease, cirrhosis in four cases. All patients underwent a liver biopsy.
  
  
  RESULTS
  All post-HES liver biopsies showed diffuse microvacuolization of Kupffer cells, which was associated with focal hepatocyte vacuolization in seven cases. The vacuoles contained periodic acid Schiff positive material at their margins and were lysosomal by electron microscopy. The clinical symptoms of hepatic disease, although difficult to interpret in cirrhotic patients, worsened after HES infusions. Portal hypertension was noted in three non-cirrhotic patients. Serum alkaline phosphatase and gammaglutamyl transferase activities were increased when compared with previous values. Eight patients died, six of them within 1-4 weeks of hepatic failure or septic shock. In the only living patient, symptoms improved after HES withdrawal.
  
  
  CONCLUSIONS
  Repeated administration of HES could favour severe portal hypertension, liver failure and sepsis, particularly in the setting of chronic liver disease. The basis of these adverse effects is the lysosomal storage of HES in Kupffer cells and hepatocytes.
authors.affiliation: Department of Hepatogastroenterology, Jean Verdier Hospital, Bondy, France.
authors.forename: C
authors.initials: C
authors.lastname: Christidis
authors.forename: F
authors.initials: F
authors.lastname: Mal
authors.forename: J
authors.initials: J
authors.lastname: Ramos
authors.forename: A
authors.initials: A
authors.lastname: Senejoux
authors.forename: P
authors.initials: P
authors.lastname: Callard
authors.forename: R
authors.initials: R
authors.lastname: Navarro
authors.forename: J C
authors.initials: JC
authors.lastname: Trinchet
authors.forename: D
authors.initials: D
authors.lastname: Larrey
authors.forename: M
authors.initials: M
authors.lastname: Beaugrand
authors.forename: C
authors.initials: C
authors.lastname: Guettier
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D001706:Biopsy; D005260:Female; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000008:administration & dosage / Q000009:adverse effects*; D006975:Hypertension, Portal / Q000139:chemically induced; D008099:Liver / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D008107:Liver Diseases / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010952:Plasma Substitutes / Q000009:adverse effects*; D019233:Retreatment / Q000009:adverse effects; D012189:Retrospective Studies; D012720:Severity of Illness Index; D014617:Vacuoles / Q000648:ultrastructure; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes; D005723:gamma-Glutamyltransferase; D000469:Alkaline Phosphatase