Serum paraoxonase activity: a new additional test for the improved evaluation of chronic liver damage.
BACKGROUND
Paraoxonase 1 (PON1) is an ester hydrolase present in serum and in the liver. The aims of the present study were to investigate the following: (a) the relationship between serum PON1 activity alterations and the degree of liver damage in patients with chronic liver disease; (b) the influence of genetic variability on serum PON1 activity; and (c) the efficacy of serum PON1 activity measurement, alone and in combination with standard liver function tests, in the assessment of liver damage.


METHODS
We studied 68 patients with liver cirrhosis, 107 patients with chronic hepatitis, and 368 apparently healthy volunteers. Baseline and salt-stimulated PON1 activities were measured by the hydrolysis of paraoxon. PON1 genotyping at positions 55 and 192 was analyzed by PCR and restriction isotyping.


RESULTS
Baseline and stimulated PON1 activities were decreased (P <0.001) in chronic hepatitis and in liver cirrhosis. PON1 activity was significantly correlated with serum total proteins, albumin, and bilirubin in patients but not in controls. There were no significant differences with respect to allele and genotype frequencies between patients and controls. The combination of baseline serum PON1 with five standard biochemical tests had a higher classification accuracy (94% of patients; 96% of controls) than the five standard tests alone (75% of patients; 96% of controls). ROC plots demonstrated a high diagnostic accuracy for baseline serum PON1 [area under the curve, 0.89 (95% confidence interval, 0.86-0.93) in chronic hepatitis and 0.96 (95% confidence interval, 0.94-0.99) in cirrhosis]. Baseline PON1 provided the highest ROC area for cirrhosis vs controls.


CONCLUSIONS
The significant decrease of PON1 activity in chronic liver diseases is related to the degree of hepatic dysfunction and not to allelic or genotypic differences. Addition of serum PON1 activity measurement to the current battery of tests may improve the evaluation of chronic liver diseases.
Ferré
Natàlia
N
Centre de Recerca Biomèdica and. Servei de Medicina Interna, Institut de Recerca en Ciències de la Salut (IRCIS), Hospital Universitari de Sant Joan, C/. Sant Joan s/n, 43201-Reus, Catalunya, Spain.
Camps
Jordi
J
Prats
Eduard
E
Vilella
Elisabet
E
Paul
Antoni
A
Figuera
Lídia
L
Joven
Jorge
J
D000328:Adult; D043303:Aryldialkylphosphatase; D004950:Esterases / Q000097:blood* / Q000235:genetics; D005260:Female; D005838:Genotype; D006521:Hepatitis, Chronic / Q000097:blood* / Q000503:physiopathology; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012372:ROC Curve
D004950:Esterases; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human