Differential Diagnosis of Conjugated Hyperbilirubinemia in Infancy (Literature Review)

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Abstract

INTRODUCTION: Conjugated hyperbilirubinemia in newborns may evidence prognostically dangerous diseases. However, the variety of causes and rarity of some of them makes differential diagnosis challenging.

AIM: To determine the order of diagnostic actions to exclude, first of all, the most probable causes of conjugated hyperbilirubinemia.

The review presents relevant information on diseases of newborns and children, running with elevation of the serum level of conjugated bilirubin. The search was carried out in PubMed, MEDLINE, eLibrary.ru databases for 2016–2023. The issues of terminology, etiology and risk factors are briefly covered. The presented pathologies include biliary atresia and Alagille syndrome, infectious and iatrogenic hepatopathies, various forms (including the new ones) of progressive familial intrahepatic cholestasis, disorders in synthesis of the primary bile acids, α1-antitrypsin deficiency, galactosemia, tyrosinemia type 1, cystic malformations, mitochondrial diseases and some other rare diseases accompanied by conjugated hyperbilirubinemia. Brief diagnostic characteristics of the presented diseases are given.

CONCLUSION: The differential diagnosis of conjugated hyperbilirubinemia in newborns and children is a complex problem requiring immediate solution by successive exclusion of the most probable diseases, first of all, biliary atresia, Alagille syndrome, infectious and iatrogenic causes.

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About the authors

Roman A. Gudkov

Ryazan State Medical University

Author for correspondence.
Email: Comancherro@mail.ru
ORCID iD: 0000-0002-4060-9692
SPIN-code: 3065-4800

MD, Cand. Sci. (Med.)

Russian Federation, Ryazan

Andrey V. Dmitriyev

Ryazan State Medical University

Email: aakavd@yandex.ru
ORCID iD: 0000-0002-8202-3876
SPIN-code: 9059-2164

MD, Dr. Sci. (Med.), Professor

Russian Federation, Ryazan

Natal'ya V. Fedina

Ryazan State Medical University

Email: k2ataka@mail.ru
ORCID iD: 0000-0001-6307-7249
SPIN-code: 2128-5240

MD, Cand. Sci. (Med.), Associate Professor

Russian Federation, Ryazan

Valeriya I. Petrova

Ryazan State Medical University

Email: gtpf17@gmail.com
ORCID iD: 0000-0001-5205-0956
SPIN-code: 2747-5836

MD, Cand. Sci. (Med.), Associate Professor

Russian Federation, Ryazan

Tat'yana A. Teryokhina

Ryazan State Medical University

Email: t080280@mail.ru
ORCID iD: 0000-0003-2667-0494
SPIN-code: 2304-4425

MD, Cand. Sci. (Med.)

Russian Federation, Ryazan

Alina E. Sologub

Ryazan State Medical University

Email: perryytkanos@mail.ru
ORCID iD: 0009-0000-6933-5165
Russian Federation, Ryazan

References

  1. Moyer V, Freese DK, Whitington PF, et al. North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Guideline for the evaluation of cholestatic jaundice in infants: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2004;39(2):115–28. doi: 10.1097/00005176-200408000-00001
  2. Gottesman LE, Del Vecchio MT, Aronoff SC. Etiologies of conjugated hyperbilirubinemia in infancy: a systematic review of 1692 subjects. BMC Pediatr. 2015;15:192. doi: 10.1186/s12887-015-0506-5
  3. Goryaynova AN, Belenovich EV, Khudyakova AA, et al. Bile thickening syndrome in newborns and young children: risk factors, therapy, prognosis. A clinical case study. Medical Council. 2020;(18):134–41. (In Russ). doi: 10.21518/2079-701X-2020-18-134-141
  4. Hertel PM, Hawthorne K, Kim S, et al. Childhood Liver Disease Research Network (ChiLDReN). Presentation and Outcomes of Infants With Idiopathic Cholestasis: A Multicenter Prospective Study. J Pediatr Gastroenterol Nutr. 2021;73(4):478–84. doi: 10.1097/mpg.0000000000003248
  5. Harpavat S, Garcia–Prats JA, Anaya C, et al. Diagnostic Yield of Newborn Screening for Biliary Atresia Using Direct or Conjugated Bilirubin Measurements. JAMA. 2020;323(12):1141–50. doi: 10.1001/jama.2020.0837
  6. Fabris L, Fiorotto R, Spirli C, et al. Pathobiology of inherited biliary diseases: a roadmap to understand acquired liver diseases. Nat Rev Gastroenterol Hepatol. 2019;16(8):497–511. doi: 10.1038/s41575-019-0156-4
  7. Averbukh LD, Wu GY. Evidence for Viral Induction of Biliary Atresia: A Review. J Clin Transl Hepatol. 2018;6(4):410–9. doi: 10.14218/jcth.2018.00046
  8. Guarino M, Perna B, Pastorelli A, et al. A case of ceftriaxone- induced liver injury and literature review. Infez Med. 2022;30(2):293–7. doi: 10.53854/liim-3002-16
  9. Ling Y, Chengxian G, Zeying F, et al. Drug-Induced Hepatic Injury in Newborns and Children in Intensive Care Unit: A Retrospective Study of China. [Preprint]. doi: 10.21203/rs.3.rs-854865/v1
  10. Volynets GV, Khavkin AI, Nikitin AV. Modern view of biliary atresia in children. Experimental and Clinical Gastroenterology. 2020;173(1): 40–55. (In Russ). doi: 10.31146/1682-8658-ecg-173-1-40-55
  11. Kohut TJ, Gilbert MA, Loomes KM. Alagille Syndrome: A Focused Review on Clinical Features, Genetics, and Treatment. Semin Liver Dis. 2021;41(4):525–37. doi: 10.1055/s-0041-1730951
  12. Gilbert MA, Loomes KM. Alagille syndrome and non-syndromic paucity of the intrahepatic bile ducts. Transl Gastroenterol Hepatol. 2021;6:22. doi: 10.21037/tgh-2020-03
  13. Gunaydin M, Bozkurter Cil AT. Progressive familial intrahepatic cholestasis: diagnosis, management, and treatment. Hepat Med. 2018;10:95–104. doi: 10.2147/hmer.s137209
  14. Henkel SA, Squires JH, Ayers M, et al. Expanding etiology of progressive familial intrahepatic cholestasis. World J Hepatol. 2019; 11(5):450–63. doi: 10.4254/wjh.v11.i5.450
  15. Mitra S, Das A, Thapa B, et al. Phenotype-Genotype Correlation of North Indian Progressive Familial Intrahepatic Cholestasis type 2 Children Shows p.Val444Ala and p.Asn591Ser Variants and Retained BSEP Expression. Fetal Pediatr Pathol. 2020;39(2):107–23. doi: 10.1080/15513815.2019.1641860
  16. Sticova E, Jirsa M, Pawłowska J. New Insights in Genetic Cholestasis: From Molecular Mechanisms to Clinical Implications. Can J Gastroenterol Hepatol. 2018;2018:2313675. doi: 10.1155/ 2018/2313675
  17. Cholestasis, Benign Recurrent Intrahepatic, 1 (BRIC1) [Internet]. Available at: https://www.malacards.org/card/cholestasis_benign_recurrent_intrahepatic_1. Accessed: 2023 February 04.
  18. Chen R, Yang F–X, Tan Y–F, et al. Clinical and genetic characte-rization of pediatric patients with progressive familial intrahepatic cholestasis type 3 (PFIC3): identification of 14 novel ABCB4 variants and review of the literatures. Orphanet J Rare Dis. 2022;17:445. doi: 10.1186/s13023-022-02597-y
  19. Lipiński P, Jankowska I. Progressive familial intrahepatic cholestasis type 3. Dev Period Med. 2018;22(4):385–9. (In Polish). doi: 10.34763/devperiodmed.20182204.385389
  20. Alam S, Lal BB. Recent updates on progressive familial intra- hepatic cholestasis types 1, 2 and 3: Outcome and therapeutic strategies. World J Hepatol. 2022;14(1):98–118. doi: 10.4254/wjh.v14.i1.98
  21. Kelly DA, editor. Diseases of the Liver and Biliary System in Children. 4th ed. Wiley Blackwell; Oxford, UK. 2017. P. 99–126.
  22. Chen H–L, Wu S–H, Hsu S–H, et al. Jaundice revisited: recent advances in the diagnosis and treatment of inherited cholestatic liver diseases. J Biomed Sci. 2018;25(1):75. doi: 10.1186/s12929-018-0475-8
  23. Henkel SA, Squires JH, Ayers M, et al. Expanding etiology of progressive familial intrahepatic cholestasis. World J Hepatol. 2019; 11(5):450–63. doi: 10.4254/wjh.v11.i5.450
  24. Wei C–S, Becher N, Friis JB, et al. New tight junction protein 2 variant causing progressive familial intrahepatic cholestasis type 4 in adults: A case report. World J Gastroenterol. 2020;26(5):550–61. doi: 10.3748/wjg.v26.i5.550
  25. Czubkowski P, Thompson RJ, Jankowska I, et al. Progressive familial intrahepatic cholestasis — farnesoid X receptor deficiency due to NR1H4 mutation: A case report. World J Clin Cases. 2021; 9(15):3631–6. doi: 10.12998/wjcc.v9.i15.3631
  26. Matarazzo L, Bianco AM, Athanasakis E, et al. MYO5B Gene Mutations: A Not Negligible Cause of Intrahepatic Cholestasis of Infancy With Normal Gamma-Glutamyl Transferase Phenotype. J Pediatr Gastroenterol Nutr. 2022;74(5):e115–21. doi: 10.1097/mpg. 0000000000003399
  27. Maslennikov DN. Narusheniye sinteza pervichnykh zhelchnykh kislot [Internet]. Genokarta. Geneticheskaya ekspertiza. Available at: https://www.genokarta.ru/disease/Narushenie_sinteza_pervichnyh_zhelchnyh_kislot. Accessed: 2023 February 04. (In Russ).
  28. Al-Hussaini AA, Setchell KDR, AlSaleem B, et al. Bile Acid Synthesis Disorders in Arabs: A 10-year Screening Study. J Pediatr Gastroenterol Nutr. 2017;65(6):613–20. doi: 10.1097/mpg.0000000000001734
  29. Castro PT, Matos APP, Werner H, et al. Prenatal Diagnosis of Caroli Disease Associated With Autosomal Recessive Polycystic Kidney Disease by 3-D Ultrasound and Magnetic Resonance Imaging. J Obstet Gynaecol Can. 2017;39(12):1176–9. doi: 10.1016/j.jogc.2017.04.041
  30. Fabris L, Fiorotto R, Spirli C, et al. Pathobiology of inherited biliary diseases: a roadmap to understand acquired liver diseases. Nat Rev Gastroenterol Hepatol. 2019;16(8):497–511. doi: 10.1038/s41575- 019-0156-4
  31. Yang XY, Zhu LP, Liu XQ, et al. Genetic diagnosis of Caroli syndrome with autosomal recessive polycystic kidney disease: a case report and literature review. Beijing Da Xue Xue Bao Yi Xue Ban. 2018;50(2):335–9. (In Chin).
  32. Gudkov RA, Dmitriev AV, Slobodyanyuk OA. Caroli syndrome in children: a brief review and clinical observation. Experimental and Clinical Gastroenterology. 2022;(10):169–74. (In Russ). doi: 10.31146/1682-8658-ecg-206-10-169-174
  33. Lasagni A, Cadamuro M, Morana G, et al. Fibrocystic liver disease: novel concepts and translational perspectives. Transl Gastroenterol Hepatol. 2021;6:26. doi: 10.21037/tgh-2020-04
  34. Özkan Gezer H. Pediatric Choledochal Cysts: Unknowns are Decreasing. In: Shehata S, editor. Pediatric Surgery, Flowcharts and Clinical Algorithms. 2019. doi: 10.5772/intechopen.84301
  35. Khan Z, Venkat VL, Soltys KA, et al. A Challenging Case of Severe Infantile Cholestasis in Alpha-1 Antitrypsin Deficiency. Pediatr Dev Pathol. 2017;20(2):176–81. doi: 10.1177/1093526616686259
  36. López de Frutos L, Cebolla JJ, de Castro–Orós I, et al. Neonatal cholestasis and Niemann-pick type C disease: A literature review. Clin Res Hepatol Gastroenterol. 2021;45(6):101757. doi: 10.1016/j.clinre.2021.101757
  37. Dana J, Girard M, Debray D. Hepatic manifestations of cystic fibrosis. Curr Opin Gastroenterol. 2020;36(3):192–8. doi: 10.1097/mog.0000000000000624
  38. Wasuwanich P, Karnsakul W. Cystic fibrosis-associated liver disease in children. Minerva Pediatr. 2020;72(5):440–7. doi: 10.23736/s0026-4946.20.05895-8
  39. Debray D, Corvol H, Housset C. Modifier genes in cystic fibrosis-related liver disease. Curr Opin Gastroenterol. 2019;35(2):88–92. doi: 10.1097/mog.0000000000000508
  40. Volynets GV, Nikitin AV, Skvortsova TA. Hereditary tyrosinemia type 1 in children. Russian Bulletin of Perinatology and Pediatrics. 2019; 64(5):69–83. (In Russ). doi: 10.21508/1027-4065-2019-64-5-69-83
  41. Bagaeva ME, Strokova TV, Mikhaylova SV, et al. Lysosomal acid lipase deficiency (cholesteryl ester storage disease): analysis of clinical cases in the Russian population. Pediatric Nutrition. 2021;19(5):35–44. (In Russ). doi: 10.20953/1727-5784-2021-5-35-44
  42. Ipatova MG, Itkis YS, Bychkov IO, et al. Mitochondrial DNA depletion syndrome in a newborn child. Pediatria. 2018;97(1):71–7. (In Russ). doi: 10.24110/0031-403X-2018-97-1-71-77
  43. Alharbi H, Priestley JRC, Wilkins BJ, et al. Mitochondrial Hepatopathies. Clin Liver Dis. 2021;18(5):243–50. doi: 10.1002/cld.1133
  44. Shen Y, Yan K, Dong M, et al. Analysis of GFM1 gene mutations in a family with combined oxidative phosphorylation deficiency 1. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2020;49(5):574–80. (In Chin). doi: 10.3785/j.issn.1008-9292.2020.10.04
  45. Guo W, Shao Y, Lang Y, et al. Identification of two novel variants of BCS1L gene in a patient with classical GRACILE syndrome. Nephrology (Carlton). 2022;27(10):810–4. doi: 10.1111/nep.14086
  46. Lee C–W, Lee J–J, Lee Y–F, et al. Clinical and molecular genetic features of cerebrotendinous xanthomatosis in Taiwan: Report of a novel CYP27A1 mutation and literature review. J Clin Lipidol. 2019; 13(6):954–9. doi: 10.1016/j.jacl.2019.10.001
  47. Golosnaya GS, Belousova TN, Novikov MYu., et al. Citrullinemia in a newborn: a case report. Russian Journal of Child Neurology. 2022;17(3):72–8. (In Russ). doi: 10.17650/2073-8803-2022-17-3-72-78
  48. Chan KL, Varughese N, Jones PM, et al. A Case of Dubin-Johnson Syndrome Presenting as Neonatal Cholestasis With Paucity of Interlobular Bile Ducts. Pediatr Dev Pathol. 2021;24(2):154–8. doi: 10.1177/1093526620980577
  49. Liu T, Zhao J, Feng J–Y, et al. Neonatal Dubin-Johnson Syndrome and its Differentiation from Biliary Atresia. J Clin Transl Hepatol. 2023;11(1):163–73. doi: 10.14218/jcth.2021.00460
  50. Pacheco ACI, Carretero LM, Torres CP, et al. NISCH syndrome: An extremely rare cause of neonatal cholestasis. J Hepatol. 2020; 73(5):1257–8. doi: 10.1016/j.jhep.2020.07.006
  51. Taylor SA, Kelly S, Alonso EM, et al. The Effects of Gestational Alloimmune Liver Disease on Fetal and Infant Morbidity and Mortality. J Pediatr. 2018;196:123–8.e1. doi: 10.1016/j.jpeds. 2017.12.054
  52. Elumalai V, Pasrija D. Zellweger Syndrome. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024. Available at: https://www.ncbi.nlm.nih.gov/books/NBK560676/. Accessed: 2023 February 04.
  53. Mutlu M, Aslan Y, Aktürk–Acar F, et al. ARC syndrome. Turk J Pediatr. 2017;59(4):487–90. doi: 10.24953/turkjped.2017.04.019
  54. Williams M, Valayannopoulos V, Altassan R, et al. Clinical, biochemical, and molecular overview of transaldolase deficiency and evaluation of the endocrine function: Update of 34 patients. J Inherit Metab Dis. 2019;42(1):147–58. doi: 10.1002/jimd.12036
  55. Revnova MO, Gaiduk IM, Mishkina TV, et al. Cholestasis in infants. Clinical Practice in Pediatrics. 2021;16(5):116–24. (In Russ). doi: 10.20953/1817-7646-2021-5-116-124
  56. Natalskiy AA, Tarasenko SV, Zaytsev OV, et al. The modern concepts problems of liver failure in surgery. I. P. Pavlov Russian Medical Biological Herald. 2014;(4):138–47. (In Russ).
  57. Romanova OA, Pechenikova VA. Polyploidies as most common chromosomal abnormalities of chorion in missed abortion. Nauka Molodykh (Eruditio Juvenium). 2021;9(2):244–57. (In Russ). doi: 10.23888/HMJ202192244-257

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