CIRCADIAN-RHYTHMS OF FIBRINOGEN, ANTITHROMBIN-III AND PLASMINOGEN IN CHRONIC LIVER-DISEASES OF INCREASING SEVERITY

Acquired deficiencies of fibrinogen, antithrombin III and plasminogen are reported in liver disease, and it is known that their plasma level s fluctuate during the day. The aim of this study was to investigate t he circadian rhythms of these three factors in chronic liver disease, Five groups of subjects were considered: (A) 15 healthy controls; (B) 15 patients with hepatic alcoholic steatosis; (C) 15 patients with chr onic active hepatitis; (D) 15 patients with compensated cirrhosis of t he liver, and (E) 15 patients with decompensated cirrhosis with ascite s. The levels of fibrinogen, antithrombin III and plasminogen were det ermined in blood samples drawn in each subject during the span of a da y every 3 h starting from midnight. The time-related values were analy zed using the 'population-mean cosinor' method. Groups A and B present ed a significant (p < 0.05) circadian rhythm for each variable, group C a significant (p < 0.05) circadian rhythm for fibrinogen and antithr ombin III and groups D and E no significant (p > 0.05) circadian rhyth ms. Statistically significant differences (p < 0.05) were demonstrated among the groups in the mean daily levels of the three variables by A NOVA, the concentrations decreasing with disease severity. These data confirm the existence of a significant diurnal periodicity in the circ ulating levels of fibrinogen, antithrombin III and plasminogen in cont rols and suggest that liver disease is associated with progressive cir cadian modifications in the temporal structure of fibrinogen, antithro mbin III and plasminogen, related to the stage of the liver disease. T he rhythm derangements may be considered markers of evolution in liver disease.