Hyperammonemia has been associated with intracranial hypertension and mortality in patients with acute liver failure (ALF). We evaluated the effect of renal replacement therapy (RRT) on serum ammonia level and outcomes in ALF. This was a multicenter cohort study of consecutive ALF patients from the United States ALF Study Group registry between January 1998 and December 2016. First, we studied the association of ammonia with hepatic encephalopathy (HE) and 21-day transplant-free survival (TFS; n = 1,186). Second, we studied the effect of RRT on ammonia for the first 3 days post study admission (n = 340) and on 21-day TFS (n = 1,186). Higher admission (n = 1,186) median ammonia level was associated with grade 3-4 HE (116 vs. 83 μmol/L) and mortality at day 21 attributed to neurological (181 vs. 90 μmol/L) and all causes (114 vs. 83 μmol/L; P < 0.001 for all). Among 340 patients with serial ammonia levels, 61 (18%) were on continuous RRT (CRRT), 59 (17%) were on intermittent RRT (IRRT), and 220 (65%) received no RRT for the first 2 days. From days 1 to 3, median ammonia decreased by 38%, 23%, and 19% with CRRT, IRRT, and no RRT, respectively. Comparing to no RRT use, whereas ammonia reduction with CRRT was significant (P = 0.007), with IRRT it was not (P = 0.75). After adjusting for year of enrollment, age, etiology, and disease severity, whereas CRRT (odds ratio [OR], 0.47 [95% confidence interval (CI), 0.26-0.82]) was associated with reduction in 21-day transplant-free all-cause mortality, IRRT (OR, 1.68 [95% CI, 1.04-2.72]) was associated with an increase. Conclusion: In a large cohort of ALF patients, hyperammonemia was associated with high-grade HE and worse 21-day TFS. CRRT was associated with a reduction in serum ammonia level and improvement of 21-day TFS.
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