Including Relative Adrenal Insufficiency in Definition and Classification of Acute on Chronic Liver Failure.

Relative adrenal insufficiency (RAI) is defined by insufficient production of cortisol relative to organ demand. RAI is frequently observed in hospitalized patients with cirrhosis, but there is disagreement over the clinical effects of RAI in these patients. We evaluated the prevalence and the clinical effects of RAI in hospitalized patients with cirrhosis.We performed a prospective study of 160 patients admitted to a hospital in Italy for acute decompensation of cirrhosis from May 2011 through September 2016. Patients were followed up until death, liver transplantation, or a maximum of 90 days. Serum and salivary levels of cortisol were meausred before and after a 1-hr short synacthen test. A diagnosis of RAI made for patients with an increase in serum cortisol of less than 9 μg/dl, after synacthen administration, in patients with baseline serum levels of cortisol below 35 μg/dl. We collected blood samples before the synacthen test and analyzed them for blood cell counts, liver and renal function, levels of C-reactive protein, and lipid profiles (total cholesterol, high-density lipoprotein cholesterol, apolipoprotein-A1).A diagnosis of RAI was made for 78 patients (49%). Age (odds ratio [OR], 0.95; P=.030), number of leukocytes (OR, 3.10; P=.006), and levels of high-density lipoprotein cholesterol (OR, 0.30; P=.039) were independently associated with RAI. Patients with RAI had a significantly higher risk of developing bacterial infections (hazard ratio [HR], 1.60; P=.038), sepsis (HR, 2.95; P=.001), septic shock (HR, 4.94; p=0.038), new organ failures (HR, 2.45; P=.014), and acute on chronic liver failure (HR=2.27; P=.037) than patients without RAI. RAI was independently associated with death within 90 days of diagnosis (subdistribution HR=4.83; P=.001). Patients with RAI and mild renal dysfunction or hepatic encephalopathy had no significant difference in cumulative incidence of 28-day mortality vs patients with acute on chronic liver failure grade 1 (25% vs 22%).We found RAI to occur in almost half of patients admitted to a hospital for acute decompensation of cirrhosis. RAI was associated with a deficit of substrates for steroidogenesis and an increase in markers of inflammation. Patients with RAI have a high risk of developing sepsis, septic shock, organ failure, and death within 90 days. RAI has similar prognostic value to non-renal organ failures.