Arterial Ammonia Independently Predicts Outcome in Acute on Chronic Liver Failure

Abstract

Background and Aim: Elevated ammonia correlates with outcome and complications in acute liver failure. However, role of arterial ammonia in predicting outcome of acute on chronic liver failure (ACLF) is unclear. We evaluated the association of arterial ammonia with complications and outcome in ACLF. Methods: Consecutive ACLF patients admitted between January 2012 and December 2015 were prospectively evaluated. Baseline arterial ammonia was estimated in all; and, in a subset of 86 patients, serial ammonia estimation was done daily for 5 consecutive days. Cox-proportional hazard analysis was used to assess predictors of outcome. Results: 291 ACLF patients were included, 223 (76.6%) males; median age (IQR) 43 (33–51) years. Commonest precipitating insult was alcohol 108 (37.1%). In-hospital mortality was 59.1% (173/291). Ammonia level ≥88.5 μmol/L at admission predicted mortality-sensitivity (63.6%), specificity (61.0%), negative predictive value (53.3%), positive predictive value (70.5%), and diagnostic accuracy (62.5%). Median ammonia level among survivors was significantly lower than in non-survivors (79 μmol/L versus 97 μmol/L; P < 0.001). Those with arterial ammonia ≥88.5 μmol/L had significantly higher mortality (110/156–70.5% versus 64/135–46.7%, P < 0.001) and encephalopathy (early encephalopathy 76–48.7% versus 40–29.6% and advanced encephalopathy 38–24.4% versus 22–16.3%, P < 0.001). Kidney and respiratory failures at admission and complications during follow-up were more frequent in patients with elevated ammonia. On multivariate Cox-proportional hazard analysis, ammonia independently predicted outcome(HR 1.010; 95%CI, 1.006–1.015, P < 0.001). Serial ammonia estimation revealed that persistently high ammonia value ≥88.5 μmol/L was associated with worsening of encephalopathy and mortality. Conclusion: Baseline arterial ammonia levels independently predict outcome in ACLF. Progressive decline of ammonia is associated with better outcome.