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Glycine Conjugation of Para-Aminobenzoic Acid (PABA): A Pilot Study of A Novel Prognostic Test in Acute Liver Failure in Children

BackgroundFulminant hepatic failure (FHF) is associated with high mortality; few patients survive without liver transplantation. It is important to have a sensitive, specific early predictor of outcome to distinguish potential survivors (S) from nonsurvivors (NS). ObjectiveBecause we had previously shown that glycine conjugation of para-aminobenzoic acid (PABA) quantitatively reflects liver function in children with chronic liver disease, in this pilot study we wanted to determine whether the measurement of the glycine conjugates of PABA could distinguish S from NS in FHF in comparison with standard prognostic indices. MethodsTwenty-four patients were studied: acute severe hepatitis (n = 7), subfulminant hepatic failure (n = 7), and FHF (n = 10). Assessment of King's College criteria, measurement of factor V and VII levels, PABA testing, and transjugular liver biopsies were performed in almost all patients within 48 hours of admission. Serum PABA and its glycine conjugates (para-aminohippurate (PAHA) and para-acetamidohippurate (PAAHA)) were measured thirty minutes after oral administration by high-pressure liquid chromatography. Poor prognostic categories as previously established in the literature were defined as factor V < 0.20U/ml, factor VII < 0.08 U/ml, % necrosis >70%, hippurate ratio = 0%, and PAHA = 0M. ResultsThe measurement of PAHA was the best predictor of a poor outcome in patients with acute liver failure with a sensitivity of 92%, and negative predictive value (NPV) of 92% compared with a sensitivity of 54% and a NPV of 63% with King's College criteria. ConclusionMeasurement of serum PAHA is the best early prognostic marker of death in children who suffer from FHF.