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Chronic acetaminophen exposure worsened outcomes for pediatric acute liver failure

Patients with pediatric acute liver failure had worse outcomes when exposed to chronic acetaminophen compared with those with single-dose exposure in a recent study.

In a multicenter, international observational cohort study, researchers evaluated 666 patients aged younger than 18 years with pediatric acute liver failure (PALF). Participants were grouped according to acetaminophen (APAP) exposure: 83 patients had chronic exposure (CE; multiple APAP doses over 2 days or longer), 85 had single-dose exposure (SE) and 498 had no exposure (NE).

All participants in the SE group had a history of APAP toxicity, the majority of which (65 cases) were related to attempted suicide. Ninety-seven percent of SE patients were diagnosed with APAP toxicity, compared with 22% of CE patients (P<.0001). Patients with CE had a lower median APAP dose than SE patients (30.8 mg/kg/day vs. 258.1 mg/kg/day; P<.0001), but the number of patients with serum APAP levels of 10 mg/L or higher was similar (66%, SE group vs. 68%, CE group; P=.87).

Patients in the CE group had lower bilirubin levels than those with NE (median 3.2 mg/dL vs. 13.1 mg/dL; P<.001), but higher levels than those with SE (2 mg/dL; P=.002). Median alanine aminotransferase levels were higher among the CE group than the NE group (2,384 IU/L vs. 855 IU/L), while SE patients had the greatest levels (5,140 IU/L) (P<.0001 for both comparisons). Twenty-one days after enrollment, the transplant-free survival rate was higher in the CE group than the NE group (68% vs. 49%; P=.008), but lower than that of the SE group (92%; P=.0004).

“PALF patients with CE do not appear to have the same favorable outcomes as the majority of children with SE,” the researchers wrote. “Rather, the results of our study suggest that a child with a history of CE is more likely to die or require liver transplantation, similar to PALF patients with other etiologies. APAP protein adduct testing in a large cohort of children with ALF is warranted to further define the importance of CE in this population.”