Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Current Pediatrics Reports
Published in: Current Pediatrics Reports 4/2023

01-12-2023

Acute Liver Failure in Neonates and Early Infancy: an Approach to Diagnosis and Management

Authors: Sanu Raja Yadav, Praveen Kumar Conjeevaram Selvakumar, Kadakkal Radhakrishnan

Published in: Current Pediatrics Reports | Issue 4/2023

Login to get access

Abstract

Purpose of Review

Acute liver failure in neonates and early infancy is an uncommon condition with varied etiology and high mortality rates. We attempt to review the recent updates on the various causes, diagnostic approach, and specific management of acute liver failure in this unique population.

Recent Findings

Better diagnostic tools including genetic/molecular techniques have expanded our understanding of etiopathogenesis of neonatal/early infantile liver failure. Multidisciplinary team-led care and rapid arrival to diagnosis can lead to better outcomes.

Summary

Neonatal/early infantile acute liver failure is a devastating condition with rapid progressive hepatocellular injury and poor prognosis compared to older children. Most common etiology includes neonatal hemochromatosis, viral hepatitis, and metabolic/genetic and ischemic causes. Structured approach to diagnostic evaluation with multidisciplinary team is needed for early diagnosis and the use of specific therapies. Liver transplantation remains a vital treatment, and prompt referral to a transplant center is crucial.
Literature
1.••
Squires RH, Shneider BL, Bucuvalas J, et al. Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group. J Pediatr. 2006;148:652-658.e2. Seminal study that set the foundation for ALF studies in children.PubMedPubMedCentralCrossRef
2.•
3.
Ng VL, Li R, Loomes KM, Leonis MA, Rudnick DA, Belle SH, Squires RH; Pediatric Acute Liver Failure Study Group (PALFSG). Outcomes of children with and without hepatic encephalopathy from the pediatric acute liver failure study group. J Pediatr Gastroenterol Nutr. 2016;63(3):357–64. https://​doi.​org/​10.​1097/​MPG.​0000000000001178​.
4.
Pal S, Curley A, Stanworth SJ. Interpretation of clotting tests in the neonate. Arch Dis Child Fetal Neonatal Ed. 2015;100:F270–4.PubMedCrossRef
5.
Durand P, Debray D, Mandel R, Baujard C, Branchereau S, Gauthier F, Jacquemin E, Devictor D. Acute liver failure in infancy: a 14-year experience of a pediatric liver transplantation center. J Pediatr. 2001;139:871–6.PubMedCrossRef
6.
Bitar R, Thwaites R, Davison S, Rajwal S, McClean P. Liver failure in early infancy: aetiology, presentation, and outcome. J Pediatr Gastroenterol Nutr. 2017;64:70–5.PubMedCrossRef
7.••
Borovsky K, Banc-Husu AM, Saul SA, Neighbors K, Kelly S, Alonso EM, Taylor SA. Applying an age-specific definition to better characterize etiologies and outcomes in neonatal acute liver failure. J Pediatr Gastroenterol Nutr. 2021;73:80–5. Most recent descriptive study focused on neonatal liver failure.PubMedCrossRef
8.
Sundaram SS, Alonso EM, Narkewicz MR, Zhang S, Squires RH. Characterization and outcomes of young infants with acute liver failure. J Pediatr. 2011;159:813-818.e1.PubMedPubMedCentralCrossRef
9.•
Feldman AG, Whitington PF. Neonatal hemochromatosis J Clin Exp Hepatol. 2013;3:313–20. Elegant review on neonatal hemochromatosis.PubMedCrossRef
10.••
Pan X, Kelly S, Melin-Aldana H, Malladi P, Whitington PF. Novel mechanism of fetal hepatocyte injury in congenital alloimmune hepatitis involves the terminal complement cascade. Hepatology. 2010;51:2061–8. Seminal paper that changed the paradigm on neonatal hemochromatosis.PubMedCrossRef
11.
Debray FG, De Halleux V, Guidi O, Detrembleur N, Gaillez S, Rausin L, Goyens P, Pan X, Whitington PF. Neonatal liver cirrhosis without iron overload caused by gestational alloimmune liver disease. Pediatrics. 2012;129:e1076–9.PubMedCrossRef
12.
Jimenez-Rivera C, Gupta A, Feberova J, de Nanassy JA, Boland MP. Successful treatment of neonatal hemochromatosis as gestational alloimmune liver disease with intravenous immunoglobulin. J Neonatal Perinatal Med. 2014;7:301–4.PubMedCrossRef
13.
Sheflin-Findling S, Annunziato RA, Chu J, Arvelakis A, Mahon D, Arnon R. Liver transplantation for neonatal hemochromatosis: analysis of the UNOS database. Pediatr Transplant. 2015;19:164–9.PubMedCrossRef
14.
Whitington PF, Kelly S. Outcome of pregnancies at risk for neonatal hemochromatosis is improved by treatment with high-dose intravenous immunoglobulin. Pediatrics. 2008;121:e1615–21.PubMedCrossRef
15.
Sundaram SS, Alonso EM, Anand R. Outcomes after liver transplantation in young infants. J Pediatr Gastroenterol Nutr. 2008;47:486–92.PubMedCrossRef
16.•
Jain AK, Anand R, Lerret S, Yanni G, Chen JY, Mohammad S, Doyle M, Telega G, Horslen S. Outcomes following liver transplantation in young infants: data from the SPLIT registry. Am J Transplant. 2021;21:1113–27. Comprehensive data review on outcomes in this unique population.PubMedCrossRef
17.
Zhang M, Wang H, Tang J, He Y, Xiong T, Li W, Qu Y, Mu D. Clinical characteristics of severe neonatal enterovirus infection: a systematic review. BMC Pediatr. 2021;21:1–12.CrossRef
18.
Sandoni M, Ciardo L, Tamburini C, Boncompagni A, Rossi C, Guidotti I, Garetti E, Lugli L, Iughetti L, Berardi A. Enteroviral infections in the first three months of life. Pathogens. 2022;11:1–14.CrossRef
19.
Ronchi A, Doern C, Brock E, Pugni L, Sánchez PJ. Neonatal adenoviral infection: a seventeen year experience and review of the literature. J Pediatr. 2014;164(529–35):e1-4.
20.
Gutierrez Sanchez LH, Shiau H, Baker JM, et al. A case series of children with acute hepatitis and human adenovirus infection. N Engl J Med. 2022;387:620–30.PubMedCrossRef
21.
Ho A, Orton R, Tayler R, et al. Adeno-associated virus 2 infection in children with non-A–E hepatitis. Nature. 2023;617:555–63.PubMedCrossRef
22.
Molleston JP, Sokol RJ, Karnsakul W, Miethke A, Horslen S, Magee JC, Romero R, Squires RH, Van Hove JLK. Evaluation of the child with suspected mitochondrial liver disease. J Pediatr Gastroenterol Nutr. 2013;57:269–76.PubMedPubMedCentralCrossRef
23.
24.
Fellman V, Kotarsky H. Mitochondrial hepatopathies in the newborn period. Semin Fetal Neonatal Med. 2011;16:222–8.PubMedCrossRef
25.•
Ayers M, Horslen SP, Gómez AM, Squires JE. Mitochondrial hepatopathy. Clin Liver Dis. 2023;26:421–38. Excellent review with recent advances and expert guidance on evaluation.CrossRef
26.
García-Cazorla A, De Lonlay P, Nassogne MC, Rustin P, Touati G, Saudubray JM. Long-term follow-up of neonatal mitochondrial cytopathies: a study of 57 patients. Pediatrics. 2005;116:1170–7.PubMedCrossRef
27.
28.
Dubern B, Broue P, Dubuisson C, Cormier-Daire V, Habes D, Chardot C, Devictor D, Munnich A, Bernard O. Orthotopic liver transplantation for mitochondrial respiratory chain disorders: a study of 5 children. Transplantation. 2001;71:633–7.PubMedCrossRef
29.
Hostetter MK, Levy HL, Winter HS, Knight GJ, Haddow JE. Evidence for liver disease preceding amino acid abnormalities in hereditary tyrosinemia. N Engl J Med. 1983;308:1265–7.PubMedCrossRef
30.
Bartlett DC, Lloyd C, McKiernan PJ, Newsome PN. Early nitisinone treatment reduces the need for liver transplantation in children with tyrosinaemia type 1 and improves post-transplant renal function. J Inherit Metab Dis. 2014;37:745–52.PubMedCrossRef
31.
Van GWG, Rodenburg IL, Harding CO, Hollak CEM, Heiner MR, Van SFJ. Long - term outcomes and practical considerations in the pharmacological management of tyrosinemia type 1. Pediatr Drugs. 2019;21:413–26.CrossRef
32.
33.
Hegarty R, Hadzic N, Gissen P, Dhawan A. Inherited metabolic disorders presenting as acute liver failure in newborns and young children: King’s College Hospital experience. Eur J Pediatr. 2015;174:1387–92.PubMedCrossRef
34.
Porta F, Pagliardini S, Pagliardini V, Ponzone A, Spada M. Newborn screening for galactosemia: a 30-year single center experience. World J Pediatr. 2015;11:160–4.PubMedCrossRef
35.
Walter JH, Collins JE, Leonard JV. Recommendations for the management of galactosaemia. UK Galactosaemia Steering Group. Arch Dis Child. 1999;80:93–6.PubMedPubMedCentralCrossRef
36.
Verhoeven NM, Wallot M, Huck JHJ, Dirsch O, Ballauf A, Neudorf U, Salomons GS, van der Knaap MS, Voit T, Jakobs C. A newborn with severe liver failure, cardiomyopathy and transaldolase deficiency. J Inherit Metab Dis. 2005;28:169–79.PubMedCrossRef
37.
Balasubramaniam S, Wamelink MM, Ngu LH, Talib A, Salomons GS, Jakobs C, Keng WT. Novel heterozygous mutations in TALDO1 gene causing transaldolase deficiency and early infantile liver failure. J Pediatr Gastroenterol Nutr. 2011;52:113–6.PubMedCrossRef
38.
Shneider BL, Setchell KD, Whitington PF, Neilson KA, Suchy FJ. Delta 4-3-oxosteroid 5 beta-reductase deficiency causing neonatal liver failure and hemochromatosis. J Pediatr. 1994;124:234–8.PubMedCrossRef
39.••
Taylor SA, Whitington PF. Neonatal acute liver failure. Liver Transplant. 2016;22:677–85. Excellent review on the etiopathogenesis.CrossRef
40.
41.•
Hadžić N, Molnar E, Height S, Kovács G, Dhawan A, Andrikovics H, Worth A, Gilmour KC. High prevalence of hemophagocytic lymphohistiocytosis in acute liver failure of infancy. J Pediatr. 2022;250:67-74.e1. Study highlights new data on etiology.PubMedCrossRef
42.
Amir AZ, Ling SC, Naqvi A, et al. Liver transplantation for children with acute liver failure associated with secondary hemophagocytic lymphohistiocytosis. Liver Transplant. 2016;22:1245–53.CrossRef
43.
Matthes-Martin S, Peters C, Königsrainer A, et al. Successful stem cell transplantation following orthotopic liver transplantation from the same haploidentical family donor in a girl with hemophagocytic lymphohistiocytosis. Blood. 2000;96:3997–9.PubMedCrossRef
44.
45.
Choudhary M, Sharma D, Dabi D, Lamba M, Pandita A, Shastri S. Hepatic dysfunction in asphyxiated neonates: prospective case-controlled study. Clin Med Insights Pediatr. 2015;9:CMPed.S21426.CrossRef
46.
Zozaya Nieto C, FernándezCaamaño B, Muñoz Bartolo G, Menéndez Suso JJ, FraucaRemacha E, ValverdeNúñez E. Presenting features and prognosis of ischemic and nonischemic neonatal liver failure. J Pediatr Gastroenterol Nutr. 2017;64:754–9.PubMedCrossRef
47.
Iacobas I, Phung TL, Adams DM, Trenor CC, Blei F, Fishman DS, Hammill A, Masand PM, Fishman SJ. Guidance document for hepatic hemangioma (infantile and congenital) evaluation and monitoring. J Pediatr. 2018;203:294-300.e2.PubMedCrossRef
48.•
Aziz H, Brown ZJ, Baghdadi A, Kamel IR, Pawlik TM. A comprehensive review of hepatic hemangioma management. J Gastrointest Surg Off J Soc Surg Aliment Tract. 2022;26:1998–2007. Excellent review on the topic.CrossRef
49.
Cheung M, Bansal S, Aw MM, Buchanan CR, Mieli-Vergani G, Dhawan A. Liver failure in a neonate with congenital adrenal hyporesponsiveness. Eur J Pediatr. 2003;162:558.PubMedCrossRef
50.
Spray CH, Mckiernan P, Waldron KE, Shaw N, Kirk J, Kelly DA. Investigation and outcome of neonatal hepatitis in infants with hypopituitarism. Acta Paediatr. 2000;89:951–4.PubMedCrossRef
51.
Haack TB, Staufner C, Köpke MG, et al. Biallelic mutations in NBAS cause recurrent acute liver failure with onset in infancy. Am J Hum Genet. 2015;97:163–9.PubMedPubMedCentralCrossRef
52.
Cousin MA, Conboy E, Wang J-S, et al. RINT1 Bi-allelic variations cause infantile-onset recurrent acute liver failure and skeletal abnormalities. Am J Hum Genet. 2019;105:108–21.PubMedPubMedCentralCrossRef
53.
Casey JP, Slattery S, Cotter M, et al. Clinical and genetic characterisation of infantile liver failure syndrome type 1, due to recessive mutations in LARS. J Inherit Metab Dis. 2015;38:1085–92.PubMedCrossRef
54.•
55.•
Thompson WS, Greenmyer JR, Lanpher BC, Brumbaugh JE, Bendel-Stenzel EM, Dimmock DP, Hobbs CA, Ibrahim SH, Hildreth AN. Ultra-rapid whole genome sequencing: a paradigm shift in the pre-transplant evaluation of neonatal acute liver failure. Liver Transplant. 2023;29:118–21. Case series highlighting recent advances with potentially significant impact on outcomes.CrossRef
56.
Leber B, Spindelboeck W, Stadlbauer V. Infectious complications of acute and chronic liver disease. Semin Respir Crit Care Med. 2012;33:80–95.PubMedCrossRef
57.
Seki S, Habu Y, Kawamura T, Takeda K, Dobashi H, Ohkawa T, Hiraide H. The liver as a crucial organ in the first line of host defense: the roles of Kupffer cells, natural killer (NK) cells and NK1.1 Ag+ T cells in T helper 1 immune responses. Immunol Rev. 2000;174:35–46.PubMedCrossRef
58.
Godbole G, Shanmugam N, Dhawan A, Verma A. Infectious complications in pediatric acute liver failure. J Pediatr Gastroenterol Nutr. 2011;53:320–5.PubMedCrossRef
59.
60.
Sundaram SS, Alonso EM, Whitington PF. Liver transplantation in neonates. Liver Transplant. 2003;9:783–8.CrossRef
61.
Sundaram SS, Alonso EM, Anand R, Study of pediatric liver transplantation research group. outcomes after liver transplantation in young infants. J Pediatr Gastroenterol Nutr. 2008;47:486–92.PubMedCrossRef
62.
Gelas T, McKiernan PJ, Kelly DA, Mayer DA, Mirza DF, Sharif K. ABO-incompatible pediatric liver transplantation in very small recipients: Birmingham’s experience. Pediatr Transplant. 2011;15:706–11.PubMedCrossRef
Metadata
Title
Acute Liver Failure in Neonates and Early Infancy: an Approach to Diagnosis and Management
Authors
Sanu Raja Yadav
Praveen Kumar Conjeevaram Selvakumar
Kadakkal Radhakrishnan
Publication date
01-12-2023
Publisher
Springer US
Published in
Current Pediatrics Reports / Issue 4/2023
Electronic ISSN: 2167-4841
DOI
https://doi.org/10.1007/s40124-023-00301-7

Other articles of this Issue 4/2023

Current Pediatrics Reports 4/2023 Go to the issue

Invited Commentary

COVID and Children: Where Do We Go from Here?

ReviewPaper

Pitfalls and Future Directions of Contemporary Pediatric Valve Surgery: the Case for Living Valve Substitutes

ReviewPaper

Risk Factors and Post-operative Management for the Bidirectional Glenn: a Literature Review

ReviewPaper

The Aetiology and Global Impact of Paediatric Sepsis

ReviewPaper

The Role of Pediatricians in Recognizing Postpartum Depression and/or Psychosis

ReviewPaper

Understanding Pediatric Dysphagia: a Multidisciplinary Approach