Acute encephalopathy without hyperammonemia has a different presentation than overt hepatic encephalopathy and displays similarly severe prognosis

Background and Aims: In cirrhosis, some patients display acute encephalopathy without hyperammonemia (NonHep E) which is not considered as overt hepatic encephalopathy (OHE). We aimed to assess the prevalence and characteristics of NonHep E and OHE in cirrhotic patients displaying acute encephalopathy, assess their respective prognosis and compare it to other causes of acute decompensation (AD) with/without hyperammonemia. Approach and Results: We conducted a retrolective analysis from a prospective cohort of patients hospitalized for AD. Hyperammonemia was defined by NH3 >50 µmol/L. Patients were divided into 4 groups: OHE (encephalopathy and NH3 >50 µmol/L: group 1), NonHep E (encephalopathy and NH3≤50 µmol/L, group 2), and 2 control groups with AD/without encephalopathy (NH3≤50 µmol/L (group 3) or NH3>50 µmol/L (group 4)). 530 patients were included (168 group 1, 76 group 2, 125 group 3, 161 group 4). Overall, 168/244 (69%) of patients with acute encephalopathy displayed OHE and 76/244 (31%) NonHep E. NonHep E patients were significantly more exposed to medications than OHE patients. One-year transplant-free survival was of 60.4%. In multivariable analysis, compared to patients with normal ammonemia and without encephalopathy, OHE was independently associated with a lower one year transplant-free survival (1.58 (95%CI 1.14–2.18, P =0.006)). OHE patients did not display a higher risk of death or transplantation than NonHep E patients (HR 1.27, 95%CI 0.91–1.77, P =0.161). Conclusion: NonHep E accounts for one third of admissions for acute encephalopathy, and displays as severe prognosis as OHE. OHE is independently associated with lower transplant-free survival at one year.