Serum ammonia improves early risk stratification beyond West Haven criteria in acute liver failure

BACKGROUND & AIMS: The prognosis of patients with acute liver failure (ALF) presenting with low grade hepatic encephalopathy (HE) defined by the West Haven criteria (WHC) is difficult to establish. We studied the association between HE severity, assessed by WHC and serum ammonia, with outcomes across different age groups. METHODS: Retrospective analysis of the prospective multicentre United States ALF Study Group registry (2000-2016). Exposures were WHC and serum ammonia on day 1 post inclusion. Endpoints were transplant-free survival (TFS) and mortality due to cerebral events on day 21. Findings were validated in a different and more recent (2010-2023) European cohort. RESULTS: Among 1092 patients, median age was 39 years and 526 (48.2%) had acetaminophen toxicity. On day 1, 968 (88.6%) patients were in the intensive care unit and 669 (61.3%) were receiving any specific organ support (ventilation vasopressors, or renal replacement therapy). TFS and cerebral mortality on day 21 were 45.2% and 6.3%, respectively. Patients with hyperammonemia (≥50 µmol/L) on day 1 had lower TFS on day 21 than others, both for WHC grades 1-2 (53.0% vs. 65.2%) and 3-4 (31.8% vs. 60.9%). Higher ammonia on day 1 was independently associated with lower TFS on day 21, irrespective of WHC grade (odds ratio of 0.958 per each 10 µmol/L increment). Ammonia on day 1 of ≥100 µmol/L showed a significant threshold effect for TFS or cerebral mortality on day 21. Patients with <40 years had the highest probability of cerebral mortality on day 21. CONCLUSIONS: In ALF, serum ammonia may help to define HE and assess prognosis earlier, irrespective of WHC grade. Patients with early serum ammonia of ≥100 µmol/L require optimized monitoring and treatment.