title: Increased elastase-alpha 1-antitrypsin complex in fulminant hepatic failure: relationship to bacterial infection and activation of coagulation.
abstract: To study the effect of infection, a frequent complication of fulminant hepatic failure (FHF), on the release of elastase from polymorphonuclear leucocytes and its inhibition in circulation we have measured the concentrations of alpha 1-antitrypsin, which binds and inhibits elastase in the circulation, and of elastase-alpha 1-antitrypsin complex, in 30 patients with FHF. Elastase-alpha 1-antitrypsin complex was significantly increased in FHF as compared to controls (303 +/- 51 micrograms/l compared to 37 +/- 5 micrograms/l; n = 10; P less than 0.001) demonstrating activation of leucocytes in FHF. Infection caused greater release of leucocyte elastase, complex levels were significantly greater in patients who were infected when compared to those who were not (463 +/- 84 micrograms/l; n = 13 compared to 180 +/- 46 micrograms/l; n = 17; P less than 0.01). Also patients who survived had significantly lower complex levels than those who did not (212 +/- 49 micrograms/l; n = 18 compared to 440 +/- 94 micrograms/l; n = 12; P less than 0.02). alpha 1-Antitrypsin activity was not significantly different from control subjects (0.99 +/- 0.06 U/ml compared to 0.97 +/- 0.05 U/ml). However alpha 1-antitrypsin activity was significantly higher in patients who survived (1.17 +/- 0.05 U/ml; n = 18) compared to those who did not (0.71 +/- 0.03 U/ml; n = 12; P less than 0.001) and patients who died had significantly lower levels than control subjects (P less than 0.01) indicating the importance of maintenance of normal inhibitor levels in patients with FHF. The leucocyte activation and release of elastase in FHF was linked to activation of the coagulation system; elastase--alpha 1-antitrypsin complex levels correlated significantly with thrombin-antithrombin III complex levels (r = 0.68; P less than 0.001) and inversely with fibrinogen (r = -0.71; P less than 0.001).
authors.affiliation: Institute of Liver Studies, King's College Hospital and King's College School of Medicine and Dentistry, London, UK.
authors.forename: P G
authors.initials: PG
authors.lastname: Langley
authors.forename: R D
authors.initials: RD
authors.lastname: Hughes
authors.forename: N
authors.initials: N
authors.lastname: Rolando
authors.forename: R
authors.initials: R
authors.lastname: Williams
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology; D001219:Aspartate Aminotransferases / Q000097:blood; D001424:Bacterial Infections / Q000175:diagnosis* / Q000209:etiology; D001663:Bilirubin / Q000032:analysis; D001777:Blood Coagulation; D003404:Creatinine / Q000097:blood; D062787:Drug Overdose; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006525:Hepatitis, Viral, Human; D006801:Humans; D008107:Liver Diseases / Q000097:blood* / Q000150:complications; D008297:Male; D009504:Neutrophils / Q000502:physiology; D010196:Pancreatic Elastase / Q000097:blood*; D011517:Prothrombin Time; D006435:Renal Dialysis; D016896:Treatment Outcome; D000515:alpha 1-Antitrypsin / Q000032:analysis*
chemical_list: D000515:alpha 1-Antitrypsin; D000082:Acetaminophen; D003404:Creatinine; D001219:Aspartate Aminotransferases; D010196:Pancreatic Elastase; D001663:Bilirubin