Lars Bossen1, Pere Ginès2,3,4, Hendrik Vilstrup1, Hugh Watson5, Peter Jepsen1,6. 1. Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark. 2. Liver Unit, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain. 3. Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain. 4. Centro de Investigaciones en Red Hepatologia y Digestivas (CIBEReHD), Barcelona, Spain. 5. Evotec ID, Lyon, France. 6. Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
Abstract
BACKGROUND AND AIM: Hyponatremia is associated with development of hepatic encephalopathy (HE), but the nature of the relationship between serum sodium and HE incidence is unknown. We examined the association between serum sodium, changes in serum sodium, and HE incidence using data from three randomized trials of satavaptan in cirrhosis patients with ascites. METHODS: During follow-up, patients were examined for HE, and serum sodium was measured regularly. We used fractional polynomials to estimate the nature of the association between current serum sodium and hazard rate of HE (e.g. with a linear, logarithmic, or exponential slope) and Cox regression to adjust for confounders. Moreover, we examined the association between serum sodium at inclusion and 30-day and 1-year cumulative risk of HE. Finally, we examined the effect of "change in serum sodium since inclusion" on the hazard rate of HE. RESULTS: We included 1116 patients of whom 302 developed HE. Median serum sodium at inclusion was 137 (interquartile range, 134-139). The lower the current serum sodium, the higher the rate of HE. Specifically, the confounder-adjusted HE hazard rate increased linearly by 8% (adjusted hazard ratio = 1.08, 95% confidence interval: 1.06-1.10) for every mmol/L decrease in serum sodium over the range of measured values. Current serum sodium had a stronger effect on the HE rate than the changes in serum sodium since inclusion. CONCLUSION: The hazard rate of HE development increased by 8% for every mmol/L decrease in serum sodium. Further, current serum sodium had a stronger effect on the HE rate than changes in serum sodium.
BACKGROUND AND AIM: Hyponatremia is associated with development of hepatic encephalopathy (HE), but the nature of the relationship between serum sodium and HE incidence is unknown. We examined the association between serum sodium, changes in serum sodium, and HE incidence using data from three randomized trials of satavaptan in cirrhosispatients with ascites. METHODS: During follow-up, patients were examined for HE, and serum sodium was measured regularly. We used fractional polynomials to estimate the nature of the association between current serum sodium and hazard rate of HE (e.g. with a linear, logarithmic, or exponential slope) and Cox regression to adjust for confounders. Moreover, we examined the association between serum sodium at inclusion and 30-day and 1-year cumulative risk of HE. Finally, we examined the effect of "change in serum sodium since inclusion" on the hazard rate of HE. RESULTS: We included 1116 patients of whom 302 developed HE. Median serum sodium at inclusion was 137 (interquartile range, 134-139). The lower the current serum sodium, the higher the rate of HE. Specifically, the confounder-adjusted HE hazard rate increased linearly by 8% (adjusted hazard ratio = 1.08, 95% confidence interval: 1.06-1.10) for every mmol/L decrease in serum sodium over the range of measured values. Current serum sodium had a stronger effect on the HE rate than the changes in serum sodium since inclusion. CONCLUSION: The hazard rate of HE development increased by 8% for every mmol/L decrease in serum sodium. Further, current serum sodium had a stronger effect on the HE rate than changes in serum sodium.
Authors: Charlotte W Wernberg; Ove B Schaffalitzky de Muckadell; Hendrik Vilstrup; Mette M Lauridsen Journal: PLoS One Date: 2019-12-12 Impact factor: 3.240