Assessment of adrenal response in patients with stable cirrhosis and ascites using different short Synacthen tests and definitions.

BACKGROUND AND AIMS: The definition of relative adrenal insufficiency (RAI) in patients with cirrhosis remains controversial. We investigated the serum and salivary cortisol (SalC) response after low-dose and standard-dose Synacthen test in patients with stable cirrhosis and ascites. METHODS: Ninety-five cirrhotic patients with ascites were prospectively evaluated from January 2014 to January 2018. Low-dose [adrenocorticotrophic hormone (ACTH): 1 µg] and standard-dose (ACTH: 250 µg) Synacthen test were successively performed. Paired serum total and saliva cortisol were taken at baseline, 30 min (low-dose test) and 60 min (standard-dose test). Salivary and Δserum total cortisol criteria included post-ACTH SalC < 12.7 ng/ml and/or SalC increase <3 ng/ml and serum total cortisol increase <9 µg/dl, respectively. RESULTS: The prevalence of RAI varied according to the definition used. SalC-defined RAI was significantly more common after low-dose than standard-dose test (54.7% vs. 20%; P < 0.001). Δserum total cortisol-defined RAI was also significantly more frequent after low-dose than standard-dose test (66.3% vs. 24.2%; P < 0.001). Considering low-dose test/SalC criteria as reference diagnostic criteria, standard-dose/salivary and Δserum total cortisol criteria showed low specificity for RAI diagnosis (43.9% and 52.7%, respectively). Survival probability was significantly lower in patients with low-dose test/SalC-defined RAI compared to those without (53.8% vs. 79.1%; P = 0.01). SalC-defined RAI after low-dose test was significantly more common than that defined after standard-dose test (72.7% vs. 30.3%; P < 0.001) among patients who died. CONCLUSION: Low-dose test/SalC definition can identify RAI in about half of patients with stable cirrhosis and ascites and is associated with increased mortality.

Conversion of Propranolol to Carvedilol Improves Renal Perfusion and Outcome in Patients With Cirrhosis and Ascites.

BACKGROUND: In recent years, concerns have been raised on the potential adverse effects of nonselective beta-blockers, and particularly carvedilol, on renal perfusion and survival in decompensated cirrhosis with ascites. We investigated the long-term impact of converting propranolol to carvedilol on systemic hemodynamics and renal function, and on the outcome of patients with stable cirrhosis and grade II/III nonrefractory ascites. PATIENTS AND METHODS: Ninety-six patients treated with propranolol for esophageal varices' bleeding prophylaxis were prospectively evaluated. These patients were randomized in a 2:1 ratio to switch to carvedilol at 12.5 mg/d (CARVE group; n=64) or continue propranolol (PROPRA group; n=32). Systemic vascular resistance, vasoactive factors, glomerular filtration rate, and renal blood flow were evaluated at baseline before switching to carvedilol and after 6 and 12 months. Further decompensation and survival were evaluated at 2 years. RESULTS: During a 12-month follow-up, carvedilol induced an ongoing improvement of systemic vascular resistance (1372±34 vs. 1254±33 dynes/c/cm5; P=0.02) along with significant decreases in plasma renin activity (4.05±0.66 vs. 6.57±0.98 ng/mL/h; P=0.01) and serum noradrenaline (76.7±8.2 vs. 101.9±10.5 pg/mL; P=0.03) and significant improvement of glomerular filtration rate (87.3±2.7 vs. 78.7±2.3 mL/min; P=0.03) and renal blood flow (703±17 vs. 631±12 mL/min; P=0.03); no significant effects were noted in the PROPRA group. The 2-year occurrence of further decompensation was significantly lower in the CARVE group than in the PROPRA group (10.5% vs. 35.9%; P=0.003); survival at 2 years was significantly higher in the CARVE group (86% vs. 64.1%; P=0.01, respectively). CONCLUSION: Carvedilol at the dose of 12.5 mg/d should be the nonselective beta-blocker treatment of choice in patients with cirrhosis and nonrefractory ascites, as it improves renal perfusion and outcome.