Increased turnover of Gc-globulin in patients with hepatic encephalopathy.
BACKGROUND
A low serum level (< 100 mg/L) of the actin-scavenger Gc-globulin is a prognostic marker of non-survival in fulminant hepatic failure (FHF). It is unknown whether decreased production or increased consumption (or both) is responsible for the low Gc-globulin levels.


METHODS
Ten patients with FHF and four patients with acute or chronic liver disease (AOCLD) with hepatic encephalopathy (HE) grades II-IV were included. Eight patients with cirrhosis (chronic liver disease, CLD) without HE served as controls. Total, free, and actin-bound Gc-globulin were measured in samples from an artery, a central vein, and a hepatic vein. In 12 patients (9 FHF, 3 AOCLD), concentrations were measured before and after high volume plasmapheresis (HVP).


RESULTS
Total Gc-globulin was reduced to 21%, 40%, and 43% of the normal level in the FHF, AOCLD, and CLD groups, respectively, whereas bound Gc-globulin was within normal range in all patients. The Gc:actin complex ratio was increased 3.8, 2.5, and 1.9-fold compared with normal levels. Total, free, and bound serum Gc-globulin levels did not differ among arterial, systemic venous, or hepatic venous blood. Total Gc-globulin rose to >100 mg/L in all patients after HVP, whereas bound Gc-globulin remained unchanged. The Gc-globulin production rate in FHF and AOCLD patients was increased to 4.1 +/- 1.3 mg/min compared to literature values of 0.6 mg/min in healthy individuals. The estimated half-life of total Gc-globulin was shorter in the patients compared to healthy individuals (127 +/- 56 min and 870 min, respectively).


CONCLUSIONS
Gc-globulin levels were reduced in patients with FHF and AOCLD because a 7-fold increase of Gc-globulin production rate could not compensate for the accelerated clearance. Bound Gc-globulin was maintained within normal levels in all circumstances studied, indicating a possible regulatory role of this parameter in the clearance of actin.
Schiødt
F V
FV
Medical Dept., Rigshospitalet, Copenhagen, Denmark. schiodt@get2net.dk
Clemmesen
J O
JO
Bondesen
S
S
Dahl
B
B
Ott
P
P
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006207:Half-Life; D006501:Hepatic Encephalopathy / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000378:metabolism*; D017093:Liver Failure / Q000097:blood / Q000378:metabolism*; D008297:Male; D014809:Vitamin D-Binding Protein / Q000097:blood / Q000378:metabolism*
D014809:Vitamin D-Binding Protein