Salvatore Piano1, Elisa Favaretto1, Marta Tonon1, Giorgia Antonelli2, Alessandra Brocca1, Antonietta Sticca1, Sara Mareso1, Enrico Gringeri3, Carla Scaroni4, Mario Plebani2, Francesco Paolo Russo5, Patrizia Burra5, Umberto Cillo3, Paolo Angeli6. 1. Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy. 2. Unit of Laboratory Medicine, Department of Medicine, University of Padova, Padova, Italy. 3. Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy. 4. Unit of Endocrinology, Department of Medicine, University of Padova, Padova, Italy. 5. Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy. 6. Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy. Electronic address: pangeli@unipd.it.
Abstract
BACKGROUND & AIMS: Relative adrenal insufficiency (RAI) is defined by insufficient production of cortisol relative to organ demand. RAI is observed frequently 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. METHODS: 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 measured before and after a 1-hour Short Synacthen Test. A diagnosis of RAI was given to patients with an increase in serum cortisol of less than 9 μg/dL, after Synacthen administration, in patients with baseline serum levels of cortisol less than 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). RESULTS: 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 associated independently 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 = .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 associated independently 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%). CONCLUSIONS: 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 nonrenal organ failures.
BACKGROUND & AIMS: Relative adrenal insufficiency (RAI) is defined by insufficient production of cortisol relative to organ demand. RAI is observed frequently 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. METHODS: 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 measured before and after a 1-hour Short Synacthen Test. A diagnosis of RAI was given to patients with an increase in serum cortisol of less than 9 μg/dL, after Synacthen administration, in patients with baseline serum levels of cortisol less than 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). RESULTS: 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 associated independently 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 = .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 associated independently 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%). CONCLUSIONS: 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 nonrenal organ failures.
Authors: Christina M Lovato; Thierry Thévenot; Sophie Borot; Vincent Di Martino; Clifford R Qualls; Frank K Urban; Richard I Dorin Journal: JHEP Rep Date: 2021-03-19