Role of ammonia in predicting the outcome of patients with acute-on-chronic liver failure

BACKGROUND: High venous ammonia (VA) values have been proven to be a part of the mechanism of hepatic encephalopathy in patients with liver cirrhosis (LC) as well as acute hepatitis. Moreover, VA has been associated with poor prognosis and high mortality in these clinical settings. However, the role of ammonia in acute-on-chronic liver failure (ACLF) has not yet been clearly established. AIM: To assess the role of VA in predicting the outcome of cirrhotic patients with ACLF in a tertiary care center. METHODS: We performed a retrospective observational study including consecutive patients with LC hospitalized for acute non-elective indications such as ascites, hepatic encephalopathy (HE), upper gastrointestinal bleeding, or bacterial infections that fulfilled the Asian Pacific Association for the Study of the Liver (APASL) criteria for ACLF. The study was conducted in “St. Spiridon” University Hospital, Iasi, Romania, a tertiary care center, between January 2017 and January 2019. The APASL ACLF Research Consortium (AARC) score was calculated and ACLF grade was established accordingly. West-haven classification was used for HE. Statistical analysis was performed using IBM SPSS version 22.0. RESULTS: Four hundred and forty-six patients were included, aged 59 (50-65) years, 57.4% men. Child-Pugh, model for end-stage liver disease (MELD) and AARC scores were 11 (10-12), 19.13 ± 6.79, and 7 (6-8), respectively. 66.4% had ACLF grade I, 31.2% ACLF grade II, and 2.5% ACLF grade III. HE was diagnosed in 83.9%, 34% grade I, 37.2% grade II, 23.5% grade III, and 5.3% grade IV. Overall mortality was 7.8%. VA was 103 (78-148) μmol/L. Receiver operating characteristic analysis showed good accuracy for the prediction of in-hospital mortality for the AARC score [Area under the curve (AUC) = 0.886], MELD score (AUC = 0.816), VA (AUC = 0.812) and a fair accuracy for the Child-Pugh score (AUC = 0.799). Subsequently, a cut-off value for the prediction of mortality was identified for VA (152.5 μmol/L, sensitivity = 0.706, 1-specificity = 0.190). Univariate analysis found acute kidney injury, severe HE (grade III or IV), VA ≥ 152.5 μmol/L, MELD score ≥ 22.5, Child-Pugh score ≥ 12.5, and AARC score ≥ 8.5 to be associated with in-hospital mortality. Multivariate analysis identified AARC score ≥ 8.5 and venous ammonia ≥ 152 μmol/L to be independent predictors of in-hospital mortality. CONCLUSION: VA could be used as an inexpensive predictor of in-hospital mortality in patients with ACLF. Patients with both ACLF and VA > 152.5 μmol/L have a high risk for a poor outcome.