Low admission values of the actin scavenger Gc-globulin are associated with
an adverse outcome in acetaminophen (paracetamol) overdose. This prospecti
ve longitudinal study including 84 patients with acetaminophen overdose cha
racterizes the temporal profile of Gc-globulin during the entire length of
hospitalization. Serum Gc-globulin (total, actin bound, and free) levels an
d actin-complex ratio were measured on admission and every 12 hours until d
ischarge. In 32 patients without hepatotoxicity (non-HEPTOX group; peak tra
nsaminase levels <1,000 U/L), total and free Gc-globulin levels and complex
ratio remained within normal range during hospitalization. Among 52 patien
ts with hepatotoxicity (HEPTOX group; peak transaminase levels >1,000 U/L),
15 patients had hepatic encephalopathy (HE), and 37 patients did not. In t
hese 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 na
dir 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 co
rrectly predicted HE in 75%, and a value greater than 120 mg/L correctly pr
edicted 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 a
gainst actin toxicity may be inadequate. A total Gc-globulin level less tha
n 120 mg/L on day 2 is a good predictor of later HE. Bound Gc-globulin is m
aintained at constant levels independent of total Gc-globulin levels, sugge
sting a balanced upregulation of the removal of bound Gc-globulin even unde
r conditions with increased actin release.