Hypochloremia as a novel adverse prognostic factor in acute liver failure

Abstract

Background and Aims Emerging evidence has identified hypochloremia as an independent predictor for mortality in multiple conditions including cirrhosis. Acute liver failure (ALF) is frequently complicated by electrolyte abnormalities. We investigated the prognostic value of hypochloremia in a large cohort of ALF patients from North America. Methods The Acute Liver Failure Study Group (ALFSG) registry is a longitudinal cohort study involving 2588 ALF patients enrolled prospectively from 32 North American academic centres. The primary outcome was a composite of 21‐day all‐cause mortality or requirement for liver transplantation (death/LT). Results Patients with hypochloremia (<98 mEq/L) had a significantly higher 21‐day mortality rate (42.1%) compared with those with normal (27.5%) or high (>107 mEq/L) chloride (28.0%) (p < .001). There was lower transplant‐free cumulative survival in the hypochloremic group than in the normo‐ or hyper‐chloremic groups (log‐rank, χ2 24.2, p < .001). Serum chloride was inversely associated with the hazard of 21‐day death/LT with multivariable adjustment for known prognostic factors (adjusted hazard ratio [aHR]: 0.977; 95% CI: 0.969–0.985; p < .001). Adding chloride to the ALFSG Prognostic Index more accurately predicted risk of death/LT in 19% of patients (net reclassification improvement [NRI] = 0.19, 95% CI: 0.13–0.25) but underestimated the probability of transplant‐free survival in 34% of patients (NRI = −0.34, 95% CI: −0.39 to −0.28). Conclusions Hypochloremia is a novel independent adverse prognostic factor in ALF. A new ALFSG‐Cl Prognostic Index may improve the sensitivity to identify patients at risk for death without LT.

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

“…Most interestingly, a higher mortality was still evident after stratifying patients according to the presence/absence of hyponatremia. Similar findings were also obtained in two other studies evaluating patients with cirrhosis at the ICU 10 or with acute liver failure 11 . Thus, we aimed to study changes in chloride in outpatients with ACLD as well as critically ill patients with cirrhosis to explore potential implications on prognosis.…”

“…Indeed, the prognostic importance of chloride changes was also confirmed in a large cohort of patients with acute liver failure, a setting that is often characterized by pronounced alterations of the acid-base homeostasis. 4,11 Therefore, hypochloremia must not be considered a bystander phenomenon in patients with liver disease, but patients with hypochloremia should be regarded as a high-risk population and need appropriate management.…”

“…Similar findings were also obtained in two other studies evaluating patients with cirrhosis at the ICU 10 or with acute liver failure. 11 Thus, we aimed to study changes in chloride in outpatients with ACLD as well as critically ill patients with cirrhosis to explore potential implications on prognosis. 6 Diagnosis of cirrhosis was based on past medical history, clinical findings, liver sonography, or liver histology, as previously described.…”

“…Results: ACLD cohort: 68% of male patients with a median MELD (adjusted for Na) of 11 (9)(10)(11)(12)(13)(14)(15)(16)(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.…”

Community-based serum chloride abnormalities predict mortality risk

“…233 [ 19 ]. Of note, some previous reports adopted this normal range [ 20 ], while other studies selected 96 mmol/l [ 6 ] or 95 [ 21 , 22 ] as the lowest normal level. Of special note is the following methodology we employed to evaluate the significance of hypochloremia in the community.…”