Higher free serum cortisol is associated with worse survival in acute variceal bleeding because of cirrhosis: a prospective study.

BACKGROUND AND AIMS: Critical illness-related corticosteroid insufficiency has been reported in acute variceal bleeding (AVB). In cirrhosis, free serum cortisol (FC) is considered optimal to assess adrenal function. Salivary cortisol (SC) is considered a surrogate for FC. We evaluated FC and its prognostic role in AVB.

METHODS: Total serum cortisol, SC, cortisol-binding globulin, and FC (Coolens' formula) were evaluated in AVB (n=38) and in stable cirrhosis (CC) (n=31). A Cox proportional hazards model was evaluated for 6-week survival.

RESULTS: In AVB, the median FC and SC levels were higher with worse liver dysfunction [Child-Pugh (CP) A/B/C: 1.59/2.62/3.26 μg/dl, P=0.019; CPA/B/C: 0.48/0.897/1.81 μg/ml, P<0.001, respectively]. In AVB compared with CC, median total serum cortisol: 24.3 versus 11.6 μg/dl (P<0.001), SC: 0.86 versus 0.407 μg/ml (P<0.001); FC 2.4 versus 0.57 μg/dl (P<0.001). In AVB, 5-day rebleeding was 10.5%, and 6-week and total mortality were 21.1 and 23.7%, respectively. Independent associations with 6-week mortality in AVB were FC at least 3.2 μg/dl (P<0.001), hepatocellular carcinoma (P<0.001), CPC (P<0.001), and early rebleeding (P<0.001). Among patients with normal cortisol-binding globulin (n=14) and albumin (n=31), the factors were hepatocellular carcinoma (P=0.003), CP (P=0.003), and FC (P=0.036). SC was also found to be an independent predictor of 6-week mortality (P<0.001). Area under the curve of FC for predicting 6-week mortality was 0.79.

CONCLUSION: Higher FC is present in cirrhosis with AVB compared with CC and is associated independently with bleeding-related mortality. However, whether high FC solely indicates the severity of illness or whether there is significant adrenal insufficiency cannot be discerned.