Pediatric acute liver failure: variations in referral timing are associated with disease subtypes

In pediatric acute liver failure (PALF), rapid referral to a transplant center (TC) is advocated. Clinical variability of PALF may influence referral timing. We aimed to analyze early or late timing of referral in relation to clinical characteristics and outcome in PALF. We conducted a retrospective, single-center, comparative analysis of clinical and liver function parameters in two PALF cohorts (n = 23 per cohort): cohort 1 (early referral, duration of in-patient care before referral (DCR) <7 days) vs. cohort 2 (late referral, DCR ≥ 7 days). Compared to late referrals, patients referred early were more frequently non-icteric and encephalopathic at initial presentation (n = 14 vs. 5 and n = 13 vs. 4, each p < 0.05). Early referred PALF patients had lower hepatic encephalopathy (HE) grades and bilirubin (grade 1 vs. 2, p < 0.02; 215 vs. 439 μmol/l, p < 0.001, respectively) but higher alanine aminotransferase (ALAT) levels (4,340 vs. 963 U/l, p < 0.001). Cumulative poor prognostic indicators were lower in early referrals (2 vs. 4, p < 0.001). In multivariate analysis, subacute liver failure (SLF >7 days between disease onset and development of encephalopathy) was independently associated with late referral (relative risk 9.48; 95 % CI 1.37–64.85, p < 0.02). Differences in survival to discharge were not significant. Conclusion: In PALF, referral timing variability is associated with distinct clinical and liver function patterns. Early recognition of prognostic indicators and of SLF may help to improve referral timing and thus PALF management.