Persistent or incident hyperammonemia is associated with poor outcomes in acute decompensation and acute-on-chronic liver failure.

Background And Aim: The effect of elevated ammonia on organ failures (OF), apart from hepatic encephalopathy, in patients with acute decompensation (AD) of cirrhosis and acute-on-chronic liver failure (ACLF) is unclear. We aimed to assess the effect of persistent or incident hyperammonemia on OF and outcomes in patients with AD and ACLF.

Methods: A total of 229 patients with ACLF and 83 with AD were included. Arterial ammonia was measured on day 1 and day 3 of admission. Persistent or incident hyperammonemia was defined as a level of ≥79.5 μmol/L on day 3. The changes in ammonia levels during the first 3 days were analyzed with respect to the complications and outcomes.

Results: At admission, the median level of arterial ammonia was higher in ACLF compared to AD patients (103 86 μmol/L,  < 0.001). Persistent or incident hyperammonemia was noted in 206 (66.0%) patients and was more frequent in ACLF compared to AD patients (70.7 53.0%, = 0.013). Patients with persistent or incident hyperammonemia, compared to those without it, developed a higher proportion of new-onset OF during hospitalization involving liver ( = 0.018), kidney ( = 0.001), brain ( = 0.005), coagulation ( = 0.036), circulation ( = 0.002), and respiratory ( = 0.003) issues and had higher 28-day mortality (log-rank test,  < 0.001). After adjustment for chronic liver failure consortium ACLF score, persistent or incident hyperammonemia (hazard ratio, 3.174) was independently associated with 28-day mortality. The presence of infection was an independent predictor of persistent or incident hyperammonemia.

Conclusion: Persistent or incident hyperammonemia during first 3 days of hospitalization in patients with AD or ACLF is associated with increased risk of OF and death.