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Transplant-free Survival in Chronic Liver Disease Presenting as Acute Liver Failure in Childhood

Di Giorgio, Angelo1; Nicastro, Emanuele1; Dalla Rosa, Davide1; Nebbia, Gabriella2; Sonzogni, Aurelio3; D’Antiga, Lorenzo1

doi: 10.1097/TP.0000000000002367
Original Clinical Science—Liver

Background. In adults, the absence of a preexisting chronic liver disease (CLD) is required to diagnose acute liver failure (ALF). The pediatric classification does not consider this aspect, thus previous studies pooled together children with ALF and children with unknown CLD presenting with acute hepatic decompensation (ALF-CLD). We aimed to compare prevalence, features, and outcome of children with ALF-CLD to those with a proper ALF.

Methods. Patients admitted between 1996 and 2017 because of ALF defined by Pediatric Acute Liver Failure criteria (raised transaminases, International Normal Ratio ≥2.0, no history of liver disease) were classified as ALF-CLD if diagnosed with autoimmune hepatitis, Wilson disease, Budd-Chiari syndrome, hepatitis B virus reactivation, inborn errors of metabolism. The others were classified as ALF.

Results. Seventy-four children (median age, 4 years; 1.0–8.8; male/female, 36/38] with ALF were found; 18 of <1 year of age were excluded. Fifty-six (median age, 6.6 years; 2.7–11.7; male/female, 23/33], 22 with ALF-CLD (autoimmune hepatitis, n = 14; Wilson disease, n = 6; inborn errors of metabolism, n = 2) and 34 with ALF (paracetamol overdose, n = 6; viral infections, n = 3; mushroom poisoning, n = 5; indeterminate, n = 20) were compared. In ALF-CLD, the median age at onset was higher, alanine aminotransferase, albumin, and International Normal Ratio levels were lower, splenomegaly, ascites, and cirrhosis were more common (all P < 0.01). On multivariate analysis, the diagnosis of ALF-CLD was an independent predictor of transplant-free survival (P = 0.006).

Conclusions. In children, ALF-CLD is common, has peculiar features, and is associated with a favorable outcome. This study suggests the need to distinguish this entity from other forms of ALF in children.

1Paediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII Bergamo, Italy.

2Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy.

3Liver and Transplant Pathology, Hospital Papa Giovanni XXIII Bergamo, Italy.

Received 4 February 2018. Revision received 14 June 2018.

Accepted 2 July 2018.

The authors declare no funding or conflict of interest.

A.D.G. participated in acquisition, analysis and interpretation of data, study concept and design, drafting of the article. E.N. participated in analysis and interpretation of data, critical revision for important intellectual content. D.D.R. participated in acquisition and analysis of data. G.N. participated in critical revision for important intellectual content. A.S. participated in critical revision for important intellectual content. L.D’A. participated in study concept and design, critical revision for important intellectual content, study supervision.

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Correspondence: Lorenzo D’Antiga, Paediatric Hepatology, Gastroenterology and Transplantation, ASST Ospedale Papa Giovanni XXIII di Bergamo, Piazza OMS1, 24127 Bergamo, Italy. (

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