Ammonia Is A Predictor of HE and Mortality In Cirrhosis and Acute On Chronic Liver Failure (ACLF)

Abstract

Background & Aim: Acute-on-chronic liver failure (ACLF) is characterized by acute deterioration of cirrhosis, systemic inflammation and multi-organ failure. While the role of ammonia in the development of HE in acute liver failure (ALF) is well established, less is known about its relationship with ACLF and the progression of HE in this context. HE in cirrhosis and ACLF results in increased mortality, however the utility of serum ammonia in predicting severity of HE or mortality remains unclear. This study aims to define: (i) the relationship between ammonia as potential predictor of survival and (ii) its role in the severity of HE in cirrhotic and ACLF patients. Methods: 248 patients with cirrhosis with and without ACLF were studied – grade 0, without ACLF (n = 106), grade 1 (n = 39), grade 2 (n = 56) and grade 3 (n = 47). Plasma ammonia levels, percentage of survival, defined as a composite of in-patient or 28 day mortality, and severity of HE (West Haven Criteria; grade 0/1 as minimum, grade 2 as moderate and grade 3/4 as severe) were measured. Results: Our patients showed higher ammonia levels correlating with higher grade of ACLF (grade 2 (85.8 ± 6.3) and 3 (94.6 ± 6.0) versus 0 (60.2 ± 2.2); P < 0.05). Moreover, higher ammonia levels correlated with more severe HE, in fact, significant differences were found between severe (grade 3/4; 92.7 ± 6.7) and the others (moderate and minimal) (P < 0.05), and between moderate (grade 2; 77.9 ± 3.9) and minimal (grade 0/1; 66.1 ± 3.0) HE (P < 0.05). Furthermore, ammonia correlated with differences between survivors (58.1 ± 1.4) and non-survivors (115.5 ± 41.9) in grade 0 ACLF (P = 0.007); no differences were found between grade 1 (65.9 ± 5.9 vs. 74.1 ± 5.2), grade 2 (84.5 ± 7.6 vs. 87.9 ± 12.0) and grade 3 (99.0 ± 12.9 vs. 93.5 ± 6.5). Finally, our data showed that the high ammonia levels in cirrhotic patients with or without ACLF predicted mortality (AUROC: 0.69, P < 0.0001). Conclusion: Our data support the important role of hyperammonemia in the pathogenesis of HE in no ACLF and ACLF patients. This study shows for the first time the ability of ammonia to predict the survival of patients with ACLF. The authors have none to declare.