title: Temporal profile of total, bound, and free Gc-globulin after acetaminophen overdose.
abstract: Low admission values of the actin scavenger Gc-globulin are associated with an adverse outcome in acetaminophen (paracetamol) overdose. This prospective longitudinal study including 84 patients with acetaminophen overdose characterizes the temporal profile of Gc-globulin during the entire length of hospitalization. Serum Gc-globulin (total, actin bound, and free) levels and actin-complex ratio were measured on admission and every 12 hours until discharge. In 32 patients without hepatotoxicity (non-HEPTOX group; peak transaminase levels < 1,000 U/L), total and free Gc-globulin levels and complex ratio remained within normal range during hospitalization. Among 52 patients with hepatotoxicity (HEPTOX group; peak transaminase levels > 1,000 U/L), 15 patients had hepatic encephalopathy (HE), and 37 patients did not. In these 2 groups, total and free Gc-globulin levels decreased to 97 and 50 mg/L and 148 and 86 mg/L, respectively (normal mean, 340 and 299 mg/L), the nadir occurring at 72 hours postoverdose. Complex ratio peaked at 60 hours at levels more than 3-fold greater than normal. Conversely, bound Gc-globulin remained within normal levels for all patients throughout the observation period. At day 2, a total Gc-globulin cutoff value of less than 120 mg/L correctly predicted HE in 75%, and a value greater than 120 mg/L correctly predicted the absence of HE in 91% of patients. In conclusion, Gc-globulin is severely stressed in patients with hepatotoxicity. Extreme values occurred at 60 to 72 hours postoverdose, a period in which Gc-globulin protection against actin toxicity may be inadequate. A total Gc-globulin level less than 120 mg/L on day 2 is a good predictor of later HE. Bound Gc-globulin is maintained at constant levels independent of total Gc-globulin levels, suggesting a balanced upregulation of the removal of bound Gc-globulin even under conditions with increased actin release.
authors.affiliation: Medical Department A, Division of Hepatology A-2121, Rigshospitalet, Copenhagen, Denmark. schiodt@get2net.dk
authors.forename: F V
authors.initials: FV
authors.lastname: Schiødt
authors.forename: P
authors.initials: P
authors.lastname: Ott
authors.forename: N
authors.initials: N
authors.lastname: Tygstrup
authors.forename: B
authors.initials: B
authors.lastname: Dahl
authors.forename: S
authors.initials: S
authors.lastname: Bondesen
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects*; D000199:Actins / Q000378:metabolism; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury; D062787:Drug Overdose; D005260:Female; D006501:Hepatic Encephalopathy / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis; D006801:Humans; D008107:Liver Diseases / Q000097:blood / Q000175:diagnosis; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012016:Reference Values; D013997:Time Factors; D014809:Vitamin D-Binding Protein / Q000097:blood* / Q000378:metabolism
chemical_list: D000199:Actins; D018712:Analgesics, Non-Narcotic; D014809:Vitamin D-Binding Protein; D000082:Acetaminophen