Angiotensinogen in chronic liver disease.

The renin substrate angiotensinogen (AGT) belongs to a supergene family of proteins that also includes alpha 1-antitrypsin (AAT) and alpha 1-antichymotrypsin (ACT), acute-phase reactants with known serine proteinase inhibitory (serpin) function. AGT lacks a known inhibitory function but is an acute-phase reactant. In this study we have compared the plasma levels, as analysed by electroimmunoassay, of AGT with AAT in patients with different types of chronic liver disease. AAT levels are regularly elevated in liver disease patients in contrast to AGT, which remains normal until late in the disease course. The AGT levels (mean +/- SD) were: in alcoholic cirrhosis (n = 19) 100 +/- 27.3%, in chronic active hepatitis (n = 14) 100 +/- 23.2%, in primary biliary cirrhosis (n = 18) 106 +/- 26.1% and in non-alcoholic cirrhosis (n = 15) 92 +/- 38.4%. Only occasionally were levels less than 50% of normal seen. In general, AGT levels were unrelated to sex and type of underlying liver disease and did not correlate with degree of hepatocellular impairment. Crossed immunoelectrophoresis showed no abnormal charge heterogeneity of AGT in patients with low levels. Our data are consistent with a dissociate expression of the homologous serpin genes in chronic liver disease. We speculate that the magnitude of the dissociated response is influenced by hormonal factors.