Disturbances in sodium and chloride homeostasis predict outcome in stable and critically ill patients with cirrhosis

Background: Hyponatremia has prognostic implications in patients with cirrhosis, and thus, has been incorporated in the 2016 MELD-UNOS update. Changes in serum chloride (Cl) are commonly perceived as 'just' parallel to changes in serum sodium, however, are less well-studied in the context of cirrhosis. Aims: To investigate whether serum chloride independently predicts outcomes in patients with advanced chronic liver disease (ACLD) and stable clinical course or with critical illness. Methods: In total, 891 patients with ACLD (defined by hepatic venous pressure gradient [HVPG] >= 6 mm Hg) were followed after HVPG measurement between 2003 and 2020 (ACLD-cohort). In total, 181 critically ill patients with cirrhosis admitted to the ICU between 2004 and 2007 were recruited for the ICU-cohort. Hypo-/hypernatremia (normal: 136-145 mmol/L) and hypo-/hyperchloremia (normal: 98-107 mmol/L) at baseline were assessed. Results: ACLD-cohort: 68% of male patients with a median MELD (adjusted for Na) of 11 (9-17) were included (Child-Pugh-stages-A/B/C: 46%/38%/16%) and followed for a median of 60 months. Lower serum chloride (adjusted average HR per mmol/L: 0.965 [95% confidence interval (95% CI): 0.945- -0.986], p = 0.001) showed a significant association with hepatic decompensation/liver-related mortality on multivariable Cox regression analysis adjusted for age, HVPG, albumin and MELD. In line, hypochloremia was significantly associated with hepatic decompensation/liver-related mortality (adjusted average HR: 1.656 [95% CI:1.267-2.163], p < 0.001). ICU-cohort: 70% of patients were male, median MELD was 31(22-39) at ICU admission (92% with Child-Pugh-stage-C). After adjusting for hypo-/hypernatremia,MELD, and blood pH, hypochloremia remained independently associated with ICU-mortality (aOR Cl: 3.200 [95%CI: 1.209-8.829], p = 0.021). Conclusion: Hypochloremia is associated with increased mortality in clinically stable and critically ill patients with cirrhosis independently of MELD including serum sodium. ICU-cohort: 70% of patients were male, median MELD was 31(22-39) at ICU admission (92% with Child-Pugh-stage-C). After adjusting for hypo-/hypernatremia,