Increased turnover of Gc-globulin in patients with hepatic encephalopathy

Background: A low serum level (< 100 mg/L) of the actin-scavenger Gc-globul in 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 wit h cirrhosis (chronic liver disease. CLD) without HE served as controls. Tot al, free, and actin-bound Gc-globulin were measured in samples from an arte ry, a central vein, and a hepatic vein. In 12 patients (9 FHF, 3 AOCLD), co ncentrations were measured before and after high volume plasmapheresis (HVP ). Results: Total Gc-globulin was reduced to 21%, 40%, and 43% of the norma l level in the FHF, AOCLD, and CLD groups, respectively, whereas bound Gc-g lobulin 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, f ree, and bound serum Gc-globulin levels did not differ among arterial, syst emic venous, or hepatic venous blood. Total Ge-globulin rose to >100 mg/L i n 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 indi viduals. The estimated half-life of total Gc-globulin was shorter in the pa tients compared to healthy individuals (127 +/- 56 min and 870 min, respect ively). Conclusions: Gc-globulin levels were reduced in patients with FHF a nd 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 r egulatory role of this parameter in the clearance of actin.