Skip to main content
SpringerLink
Log in

Children with Chronic Liver Disease

  • Chapter
  • First Online:
Frailty in Children

  • 301 Accesses

Abstract

The principal causes of frailty in children with chronic liver diseases are cholestatic liver disorders, chronic inflammatory liver diseases, metabolic liver disorders, and nutritional metabolic liver damage.

The early recognition of cholestasis in an infant is crucial since neonatal cholestasis may be the presenting sign of severe hepatobiliary or metabolic dysfunction. Next-generation gene-sequencing technologies allowed to expand the spectrum of genetic causes of neonatal cholestasis and reduce the need for invasive procedures. Despite the recent advance in diagnosis and treatment, chronic cholestatic disorders account for almost 60% of all pediatric liver transplants. Autoimmune liver diseases represent, in the actual scenario in industrialized countries, one of the main causes of chronic liver diseases in the pediatric setting. The diagnosis is based on the combination of biochemical and histological parameters and the exclusion of other liver diseases. It is a relatively rare but devastating disease, which progresses rapidly unless immunosuppressive treatment is started promptly. Standard therapy consists of a combination of corticosteroids and azathioprine, which is efficacious in 80% of patients. Alternative therapies are increasingly being explored in patients who do not respond to the standard treatment and/or experience intolerable side effects. Metabolic liver disorders represent about 10–15% of acute liver failure in infants and children and approximately 10% of pediatric liver transplants. The precocity of the diagnosis influences the prognosis of these children.

Nonalcoholic fatty liver disease (NAFLD) represents the most common cause of chronic liver disease in children and adolescents. Simple hepatic steatosis is usually a benign condition, but in some cases, it progresses to more advanced forms of liver injury, characterized by the presence of inflammation [nonalcoholic steatohepatitis (NASH)] and various degrees of fibrosis up to cirrhosis, predisposing to liver failure and/or hepatocellular carcinoma. Several studies identified insulin resistance, with or without obesity, as the underlying mechanism associated with NAFLD and identified NAFLD as the hepatic expression of metabolic syndrome.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Grimaldi C, Spada M, Maggiore G. Liver transplantation in children: an overview on organ allocation and surgical management. Curr Pediatr Rev. 2021;17(4):245–52. https://doi.org/10.2174/1573396317666210604111538.

    Article  PubMed  Google Scholar 

  2. Lane E, Murray KF. Neonatal cholestasis. Pediatr Clin N Am. 2017;64:621–39.

    Article  Google Scholar 

  3. Fawaz R, Baumann U, Ekong U, et al. Guideline for the evaluation of cholestatic jaundice in infants: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2017;64:154–68.

    Article  CAS  PubMed  Google Scholar 

  4. Ranucci G, Della Corte C, Alberti D, et al. Diagnostic approach to neonatal and infantile cholestasis: a position paper by the SIGENP liver disease working group. Dig Liv Dis. 2021;54(1):40–53.

    Article  Google Scholar 

  5. Feldman AG, Sokol RJ. Recent developments in diagnostics and treatment of neonatal cholestasis. Semin Pediatr Surg. 2020;29:150945.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Chardot C. Biliary atresia. Orphanet J Rare Dis. 2006;26:1–28.

    Google Scholar 

  7. Shneider BL, Brown MB, Haber B, Biliary Atresia Research Consortium, et al. A multicenter study of the outcome of biliary atresia in the United States 1997 to 2000. J Pediatr. 2006;148:467–74.

    Article  PubMed  Google Scholar 

  8. Hartley JL, Davenport M, Kelly DA. Biliary atresia. Lancet. 2009;374:1704–13.

    Article  PubMed  Google Scholar 

  9. Petersen C, Davenport M. Aetiology of biliary atresia what is actually known? Orphanet J Rare Dis. 2013;8:128.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Asai A, Miethke A, Bezerra JA. Pathogenesis of biliary atresia: defining biology to understand clinical phenotypes. Nat Rev Gastroenterol Hepatol. 2015;12:342–52.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Serinet MO, Wildhaber BE, Broué P, et al. Impact of age at Kasai operation on its results in late childhood and adolescence: a rational basis for biliary atresia screening. Pediatrics. 2009;123:1280–6.

    Article  PubMed  Google Scholar 

  12. Hsiao CH, Chang MH, Chen HL, et al. Universal screening for biliary atresia using an infant stool color card in Taiwan. Hepatology. 2008;47:1233–40.

    Article  PubMed  Google Scholar 

  13. Meyers R, Book LS, O’Gorman MA, et al. High-dose steroids, ursodeoxycholic acid, and chronic intravenous antibiotics improve bile flow after Kasai procedure in infants with biliary atresia. J Pediatr Surg. 2003;38:406–11.

    Article  PubMed  Google Scholar 

  14. Decharun K, Leys CM, West KW, et al. Prophylactic antibiotics for prevention of cholangitis in patients with biliary atresia status post-Kasai portoenterostomy: a systematic review. Clin Pediatr (Phila). 2016;55:66–72.

    Article  PubMed  Google Scholar 

  15. Davenport M, Stringer MD, Tizzard SA, et al. Randomized, double-blind, placebo-controlled trial of corticosteroids after Kasai portoenterostomy for biliary atresia. Hepatology. 2007;46:1821–7.

    Article  CAS  PubMed  Google Scholar 

  16. Bezerra JA, Spino C, Magee JC, Childhood Liver Disease Research and Education Network (ChiLDREN), et al. Use of corticosteroids after hepatoportoenterostomy for bile drainage in infants with biliary atresia: the START randomized clinical trial. JAMA. 2014;311:1750–9.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Bull LN, Thompson RJ. Progressive familial intrahepatic cholestasis. Clin Liver Dis. 2018;22:657–69.

    Article  PubMed  Google Scholar 

  18. Jacquemin E. Progressive familial intrahepatic cholestasis. Clin Res Hepatol Gastroenterol. 2012;36(Suppl 1):S26–35.

    Article  CAS  PubMed  Google Scholar 

  19. Vitale G, Gitto S, Raimondi F, Mattiaccio A, et al. Cryptogenic cholestasis in young and adults: ATP8B1, ABCB11, ABCB4, and TJP2 gene variants analysis by high-throughput sequencing. J Gastroenterol. 2018;53:945–58.

    Article  CAS  PubMed  Google Scholar 

  20. Gonzales E, Taylor SA, Davit-Spraul A, et al. MYO5B mutations cause cholestasis with normal serum gamma-glutamyl transferase activity in children without microvillous inclusion disease. Hepatology. 2017;65:164–73.

    Article  CAS  PubMed  Google Scholar 

  21. Gomez-Ospina N, Potter CJ, Xiao R, et al. Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis. Nat Commun. 2016;7:10713.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Warthen DM, Moore ED, Kamath BM, et al. Jagged1 (JAG1) mutations in Alagille syndrome: increasing the mutation detection rate. Hum Mutat. 2006;27:436–43.

    Article  CAS  PubMed  Google Scholar 

  23. Kamath BM, Baker A, Houwen R, et al. Systematic review: the epidemiology, natural history, and burden of Alagille syndrome. J Pediatr Gastroenterol Nutr. 2018;67:148–56.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Fujishiro J, Suzuki K, Watanabe M, et al. Outcomes of Alagille syndrome following the Kasai operation: a systematic review and meta-analysis. Pediatr Surg Int. 2018;34:1073–7.

    Article  PubMed  Google Scholar 

  25. Shneider BL, et al. Placebo-controlled randomized trial of an intestinal bile salt transport inhibitor for pruritus in Alagille syndrome. Hepatol Commun. 2018;2:1184–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Liberal R, Vergani D, Mieli-Vergani D. Pediatric autoimmune liver disease. Dig Dis. 2015;33S2:36–46.

    Article  Google Scholar 

  27. Maggiore G, Socie G, Sciveres M, et al. Seronegative autoimmune hepatitis in children: spectrum of disorders. Dig Liver Dis. 2016;48:785–91.

    Article  PubMed  Google Scholar 

  28. Longhi MS, Ma Y, Mieli-Vergani G, Vergani D. Aetiopathogenesis of autoimmune hepatitis. J Autoimmun. 2010;34:7–14.

    Article  CAS  PubMed  Google Scholar 

  29. Mieli-Vergani G, Vergani D, Baumann U, et al. Diagnosis and management of pediatric autoimmune liver disease: ESPGHAN hepatology committee position statement. J Pediatr Gastroenterol Nutr. 2018;66:345–60.

    Article  PubMed  Google Scholar 

  30. Mileti E, Rosenthal P, Peters MG. Validation and modification of simplified diagnostic criteria for autoimmune hepatitis in children. Clin Gastroenterol Hepatol. 2012;10:417–421.e1.

    Article  PubMed  Google Scholar 

  31. Sciveres M, Nastasio S, Maggiore G. Novel diagnostic and therapeutic strategies in juvenile autoimmune hepatitis. Front Pediatr. 2019;7:382.

    Google Scholar 

  32. Di Giorgio A, Vergani D, Mieli-Vergani G. Cutting edge issues in juvenile sclerosing cholangitis. Dig Liver Dis. 2021;54:417–27. https://doi.org/10.1016/j.dld.2021.06.028.

    Article  CAS  PubMed  Google Scholar 

  33. Nastasio S, Matarazzo L, Sciveres M, Maggiore G. Giant cell hepatitis associated with autoimmune hemolytic anemia: an update. Transl Gastroenterol Hepatol. 2021;6:25.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Darwish AA, McKiernan P, et al. Paediatric liver transplantation for metabolic disorder. Part 1: liver-based metabolic disorders without liver lesions. Clin Res Hepatol Gastroenterol. 2011;35:194–203.

    Article  PubMed  Google Scholar 

  35. Darwish AA, McKiernan P, et al. Paediatric liver transplantation for metabolic disorder. Part 2: metabolic disorders with liver lesions. Clin Res Hepatol Gastroenterol. 2011;35:271–80.

    Article  PubMed  Google Scholar 

  36. Sze YK, Dhawan A, Taylor RM, Bansal S, Mieli-Vergani G, Rela M, Heaton N. Pediatric liver transplantation for metabolic liver disease: experience at King’s College Hospital. Transplantation. 2009;15(87):87–93.

    Article  Google Scholar 

  37. Häberle J, Boddaert N, Burlina A, et al. Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphanet J Rare Dis. 2012;29:7–32.

    Google Scholar 

  38. Yu L, Rayhill SC, Hsu EK, Landis CS. Liver transplantation for urea cycle disorders: analysis of the united network for organ sharing database. Transplant Proc. 2015;47:2413–8.

    Article  CAS  PubMed  Google Scholar 

  39. Morrow G, Tanguay RM. Biochemical and clinical aspects of hereditary tyrosinemia type 1. Adv Exp Med Biol. 2017;959:9–21.

    Article  CAS  PubMed  Google Scholar 

  40. McKiernan P. Liver transplantation for hereditary tyrosinemia type 1 in the United Kingdom. Adv Exp Med Biol. 2017;959:85–91.

    Article  CAS  PubMed  Google Scholar 

  41. Mazariegos GV, Morton DH, Sindhi R, et al. Liver transplantation for classical maple syrup urine disease: long-term follow-up in 37 patients and comparative united network for organ sharing experience. J Pediatr. 2012;160:116–21.

    Article  PubMed  Google Scholar 

  42. Badell IR, Hanish SI, Hughes CB, Hewitt WR, Chung RT, Spivey JR, Knechtle SJ. Domino liver transplantation in maple syrup urine disease: a case report and review of the literature. Transplant Proc. 2013;45:806–9.

    Article  CAS  PubMed  Google Scholar 

  43. Fraser JL, Venditti CP. Methylmalonic and propionic acidemias: clinical management update. Curr Opin Pediatr. 2016;28:682–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Barshes NR, Vanatta JM, Patel AJ, et al. Evaluation and management of patients with propionic acidemia undergoing liver transplantation: a comprehensive review. Pediatr Transplant. 2006;10:773–81.

    Article  PubMed  Google Scholar 

  45. Bouteldja N, Timson DJ. The biochemical basis of hereditary fructose intolerance. J Inherit Metab Dis. 2010;33:105–12.

    Article  CAS  PubMed  Google Scholar 

  46. Wong D. Hereditary fructose intolerance. Mol Genet Metab. 2005;85:165–7.

    CAS  PubMed  Google Scholar 

  47. Elsas LJ, Langley S, Steele E, et al. Galactosemia: a strategy to identify new biochemical phenotypes and molecular genotypes. Am J Hum Genet. 1995;56:630–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Tada H, Takamura M, Kawashiri MA. Familial hypercholesterolemia: a narrative review on diagnosis and management strategies for children and adolescents. Vasc Health Risk Manag. 2021;17:59–67.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Ishigaki Y, Kawagishi N, Hasegawa Y, et al. Liver transplantation for homozygous familial hypercholesterolemia. J Atheroscler Thromb. 2019;26:121–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Pastores GM, Hughes DA. Lysosomal acid lipase deficiency: therapeutic options. Drug Des Dev Ther. 2020;14:591–601.

    Article  CAS  Google Scholar 

  51. Socha P, Janczyk W, Dhawan A, et al. Wilson’s disease in children: a position paper by the Hepatology Committee of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2018;66:334–44.

    Article  PubMed  Google Scholar 

  52. Dhawan A, Taylor RM, Cheeseman P, De Silva P, Katsiyiannakis L, Mieli-Vergani G. Wilson’s disease in children: 37-year experience and revised King’s score for liver transplantation. Liver Transpl. 2005;11:441–8.

    Article  PubMed  Google Scholar 

  53. Hadžić N, Baumann U, McKiernan P, McLin V, Nobili V. Long-term challenges and perspectives of pre-adolescent liver disease. Lancet Gastroenterol Hepatol. 2017;2:435–45.

    Article  PubMed  Google Scholar 

  54. Vajro P, Lenta S, Socha P, et al. Diagnosis of nonalcoholic fatty liver disease in children and adolescents: position paper of the ESPGHAN Hepatology Committee. J Pediatr Gastroenterol Nutr. 2012;54:700–13.

    Article  PubMed  Google Scholar 

  55. Furthner D, Weghuber D, Dalus C, Lukas A, Stundner-Ladenhauf HN, Mangge H, Pixner T. Non-alcoholic fatty liver disease (NAFLD) in children with obesity: narrative review and research gaps. Horm Res Paediatr. 2021;95:167–76. https://doi.org/10.1159/000518595.

    Article  CAS  PubMed  Google Scholar 

  56. Mann JP, Raponi M, Nobili V. Clinical implications of understanding the association between oxidative stress and pediatric NAFLD. Expert Rev Gastroenterol Hepatol. 2017;11:371–82.

    Article  CAS  PubMed  Google Scholar 

  57. Nobili V, Alisi A, Mosca A, et al. Hepatic farnesoid X receptor protein level and circulating fibroblast growth factor 19 concentration in children with NAFLD. Liver Int. 2018;38:342–9.

    Article  CAS  PubMed  Google Scholar 

  58. Carpino G, Pastori D, Baratta F, et al. PNPLA3 variant and portal/periportal histological pattern in patients with biopsy-proven non-alcoholic fatty liver disease: a possible role for oxidative stress. Sci Rep. 2017;7:15756.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Mangge H, Baumgartner BG, Zelzer S, et al. Patatin-like phospholipase 3 (rs738409) gene polymorphism is associated with increased liver enzymes in obese adolescents and metabolic syndrome in all ages. Aliment Pharmacol Ther. 2015;42:99–105.

    Article  CAS  PubMed  Google Scholar 

  60. Di Martino M, Koryukova K, Bezzi M. Imaging features of non-alcoholic fatty liver disease in children and adolescents. Children (Basel). 2017;4:73.

    PubMed  Google Scholar 

  61. Garcovich M, Veraldi S, Di Stasio E, et al. Liver stiffness in pediatric patients with fatty liver disease: diagnostic accuracy and reproducibility of shear-wave elastography. Radiology. 2017;283:820–7.

    Article  PubMed  Google Scholar 

  62. Dezsőfi A, Baumann U, Dhawan A, et al. Liver biopsy in children: position paper of the ESPGHAN Hepatology Committee. J Pediatr Gastroenterol Nutr. 2015;60:408–20.

    Article  PubMed  Google Scholar 

  63. Alkhouri N, De Vito R, Alisi A, et al. Development and validation of a new histological score for pediatric non-alcoholic fatty liver disease. J Hepatol. 2012;57:1312–8.

    Article  PubMed  Google Scholar 

  64. Vos MB, Abrams SH, Barlow SE, et al. NASPGHAN clinical practice guideline for the diagnosis and treatment of nonalcoholic fatty liver disease in children: recommendations from the Expert Committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). J Pediatr Gastroenterol Nutr. 2017;64:319–34.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Nobili V, Bedogni G, Alisi A, Pietrobattista A, Risé P, Galli C, Agostoni C. Docosahexaenoic acid supplementation decreases liver fat content in children with non-alcoholic fatty liver disease: double-blind randomised controlled clinical trial. Arch Dis Child. 2011;96:350–3.

    Article  PubMed  Google Scholar 

  66. Della Corte C, Carpino G, De Vito R, et al. Docosahexanoic acid plus vitamin D treatment improves features of NAFLD in children with serum vitamin D deficiency: results from a single centre trial. PLoS One. 2016;11:e0168216.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Alisi A, Bedogni G, Baviera G, et al. Randomised clinical trial: the beneficial effects of VSL#3 in obese children with non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2014;39:1276–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hepatogastroenterology, Nutrition, Digestive Endoscopy and Liver Transplant Unit, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy

    Giuseppe Maggiore, Claudia Della Corte, Daniela Liccardo, Antonella Mosca & Andrea Pietrobattista

Authors
  1. Giuseppe Maggiore
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Claudia Della Corte
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniela Liccardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Antonella Mosca
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andrea Pietrobattista
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giuseppe Maggiore .

Editor information

Editors and Affiliations

  1. Pediatric Surgery Unit, Sant’Orsola Hospital IRCCS, University of Bologna, Bologna, Italy

    Mario Lima

  2. Pediatric Intensive Care Unit, Sant’Orsola Hospital IRCCS, University of Bologna, Bologna, Italy

    Maria Cristina Mondardini

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Maggiore, G., Corte, C.D., Liccardo, D., Mosca, A., Pietrobattista, A. (2023). Children with Chronic Liver Disease. In: Lima, M., Mondardini, M.C. (eds) Frailty in Children. Springer, Cham. https://doi.org/10.1007/978-3-031-24307-3_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-24307-3_6

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-24306-6

  • Online ISBN: 978-3-031-24307-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation