Plasma Esterase Activity in Patients With Liver Disease and the Nephrotic Syndrome

Abstract

An increasing amount of evidence has been accumulated (1-3) which indicates that the albumin of the plasma is formed in the liver. The fact that the degree of albumin depression correlates well with the severity of liver involvement in patients with various types of liver disease (4) is strong evidence in favor of such a concept. In view of the significance of the metabolic and oncotic effects of the albumin level of the plasma in determining the course of patients with various types of hypoproteinemla, it would appear to be of special importance to obtain information regarding albumin synthesis in these patients in an attempt to discover possible remediable defects. Direct studies of albumin turnover have yielded some information, but the picture in cirrhosis and nephrosis is often obscured by continued loss of albumin in ascitic fluid or urine. The therapeutic use of concentrated solutions of human albumin has made it even more difficult to determine the rate of production of albumin and to evaluate the changes brought about by such therapy. The use of radioactive and isotope techniques has not as yet been feasible. Two other plasma proteins, fibrinogen and prothrombin, also have been shown to be formed by the liver (5, 6). To this list it is now possible to add a fourth protein appearing in the plasma and synthesized by the liver, namely plasma esterase.The possibility arose that, through a study in various hypoproteinemic states of the other proteins synthesized by the liver and their changes during therapy, information could be obtained regarding the general formation of proteins by the liver which might be applicable to the problem of albumin synthesis.Of the group of liver proteins the plasma esterase lends itself most readily to accurate estimation. In addition, the regeneration of this enzyme can be studied in various pathological states, following its destruction by a parenteral injection of diisopropyl fluorophosphate (DFP). This material is an extremely powerful and specific inhibitor of the esterase group of enzymes. Several observers (7,8) have demonstrated conclusively that these enzymes are irreversibly destroyed beth in ~o and in ~/vo by DFP. Comroe, Todd, and Koelle (8), in connection with their use of this material in patients with myasthenia gravis, studied the regeneration of plasma esterase following its destruction by DFP. Wescoe (9) and Grob (10) have independently applied this technique to the study of patients with liver disease. 325 on

Plasma Cholinesterase Activity in Liver Disease: Its Value as a Diagnostic Test of Liver Function Compared With Flocculation Tests and Plasma Protein Determinations 1

“…We have found that this is evident particularly in those cases with portal cirrhosis, three of which had negative flocculation tests during intermittent observations throughout a period of 12 months; in contrast, low values for plasma cholinesterase activity were observed in all patients. Kunkel and Ward (9) have already drawn attention to the close relation between the low plasma albumin and low plasma cholinesterase values in chronic liver disease, and we have confirmed this by serial estimations carried out on several of our patients over periods of 12 months or more. We have failed to observe any such marked relation, however, in acute liver disease, and we consider that the conclusions of Levine and Hoyt (25) do not merit the assumption that if the serum albumin' level is low, the serum cholinesterase level must also be low.…”

Serum cholinesterase is an excellent biomarker of liver cirrhosis

“…1 Serum cholinesterase (ChE) appears to originate in the liver and is closely associated with the synthesis of serum albumin. 2,3,4 It has been shown that even very low pre-liver transplant serum cholinesterase levels improve by second week after a successful liver transplantation, thus confirming the hepatic origin of this enzyme. 5 Several workers as early as 1950s, have studied the value of serum cholinesterase estimation as a test of liver function, particularly to assess progress of chronic liver disease.…”

The Use of Concentrated Human Serum Albumin in the Treatment of Cirrhosis of the Liver 1

“…Estimation of serum esterase activity was carried out in the Warburg manometric apparatus and the results expressed in terms of the amount of CO2 released from bicarbonate buffer following the hydrolysis of acetyl choline (13). The normal range is 40-80 mm.…”