Hyperbilirubinemia: pathologist's view
DOI:
https://doi.org/10.52784/27112330.157Keywords:
jaundice, neonatal jaundice, hyperbilirubinemia, viral hepatitis, primary biliary cholangitis, autoimmune hepatitis, biopsy, histopathology, colestasis.Abstract
Normal serum bilirubin levels in adults range from 0.3 mg/dL to 1.2 mg/dL, and its value is determined by the rate of hepatic uptake, conjugation, and excretion. Jaundice becomes apparent when serum bilirubin levels rise above 2.5 mg/dL to 3.5 mg/dL and is an indicator of underlying disease. Bile is produced by hepatocytes and flows from the canaliculi, Hering's canals, intrahepatic bile ducts, and right and left hepatic ducts to the duodenum. Pathologically, any condition that leads to intrahepatic accumulation of bile due to hepatocellular dysfunction or biliary obstruction, generates cholestasis, which is observed in liver biopsy as the accumulation of greenish-brown deposits of bile pigment in hepatocytes, with dilated canaliculi. The causes of intrahepatic cholestasis are diverse and include diseases such as primary biliary cholangitis and primary sclerosing cholangitis, autoimmune hepatitis, viral hepatitis, and drug toxicity. This review aims to analyze some types of hyperbilirubinemia, highlighting their histopathological characteristics.
Downloads
References
Pinto-Fuentes I. Capítulo 14. Ictericia. In: Alcalá-Minagorre PJ, Alonso-Salas MT, Álvarez-Calatayud G, et al, eds. Protocolos diagnóstico-terapéuticos de urgencias pediátricas SEUP-AEP. Madrid, Ergon: Sociedad Española de Urgencias de Pediatría, Asociación Española de Pediatría; 2010. p. 115-123.
Quesada LD, Zamora H, Martén A. El enfoque del paciente ictérico. Acta Med Costarric 2005;47:15-23.
Caballería L, Parés A. Un enfermo ictérico. Med Integral 2003;41:70-78.
Muchowski KE. Evaluation and treatment of neonatal hyperbilirubinemia. Am Fam Physician 2014;89:873-878.
Aggarwal R, Goel A. Hepatitis A: epidemiology in resource-poor countries. Curr Opin Infect Dis 2015;28:488-496. https://doi.org/10.1097/qco.0000000000000188.
Linder KA, Malani PN. Hepatitis A. JAMA 2017;318:2393. https://doi.org/10.1001/jama.2017.17244.
Jain D, Torres R, Celli R, Koelmel J, Charkoftaki G, Vasiliou V. Evolution of the liver biopsy and its future. Transl Gastroenterol Hepatol 2021;6:20. https://doi.org/10.21037/tgh.2020.04.01.
Winger J, Michelfelder A. Diagnostic approach to the patient with jaundice. Prim Care 2011;38:469-482. https://doi.org/10.1016/j.pop.2011.05.004.
Johnson KD, Laoveeravat P, Yee EU, Perisetti A, Thandassery RB, Tharian B. Endoscopic ultrasound guided liver biopsy: Recent evidence. World J Gastrointest Endosc 2020;12:83-97. https://doi.org/10.4253/wjge.v12.i3.83.
Khalifa A, Rockey DC. The utility of liver biopsy in 2020. Curr Opin Gastroenterol 2020;36:184-191. https://doi.org/10.1097/mog.0000000000000621.
Kathpalia P, Ahn J. Assessment of jaundice in the hospitalized patient. Clin Liver Dis 2015;19:155-170. https://doi.org/10.1016/j.cld.2014.09.009.
Roche SP, Kobos R. Jaundice in the adult patient. Am Fam Physician 2004;69:299-304.
García GC. Fisiopatología de la colestasis. Med Int Mex 2006;22:411-421.
Di Ciaula A, Garruti G, Lunardi-Baccetto R, Molina-Molina E, Bonfrate L, Wang DQ, et al. Bile acid physiology. Ann Hepatol 2017;16:S4-14. https://doi.org/10.5604/01.3001.0010.5493.
Mazzi-Gonzales de Prada E. Hiperbilirrubinemia neonatal. Rev Soc Bol Ped 2005;44:26-35.
Chiang JYL, Ferrell JM. Bile acid metabolism in liver pathobiology. Gene Expr 2018;18:71-87. https://doi.org/10.3727/105221618x15156018385515.
Joseph A, Samant H. Jaundice. StatPearls. Treasure Island (FL): StatPearls Publishing; 2022. Acceso 15 de enero de 2022. Disponible en https://www.ncbi.nlm.nih.gov/books/NBK544252/.
Fargo MV, Grogan SP, Saguil A. Evaluation of jaundice in adults. Am Fam Physician 2017;95:164-168.
Arab JP, Arrese M, Singal AK. Diagnosis of alcohol-associated hepatitis: When is liver biopsy required? Clin Liver Dis 2021;25:571-584. https://doi.org/10.1016/j.cld.2021.03.003.
Solís-Herruzo JA. Current indications of liver biopsy. Rev Esp Enferm Apar Dig 2006;98:122-139.
Feinstone SM, Kapikian AZ, Purceli RH. Hepatitis A: detection by immune electron microscopy of a viruslike antigen associated with acute illness. Science 1973;182:1026-1028. https://doi.org/10.1126/science.182.4116.1026.
Gust ID, Feinstone SM. Hepatitis A. 1st ed. Florida, USA: CRC Press; 2017. p. 249. Disponible en: https://www.taylorfrancis.com/books/mono/10.1201/9781351073172/hepatitis-ian-gust-stephen-feinstone.
Inoue K, Yoshiba M, Yotsuyanagi H, Otsuka T, Sekiyama K, Fujita R. Chronic hepatitis A with persistent viral replication. J Med Virol 1996;50:322-324. https://onlinelibrary.wiley.com/doi/10.1002/(SICI)1096-9071(199612)50:4%3C322::AID-JMV7%3E3.0.CO;2-A
Morillas RM, Bargalló AN. Hepatitis autoinmune. Semin Fund Esp Reumatol 2008;9:166-175. https://doi.org/10.1016/S1577-3566(08)74608-6.
European Association for the Study of the Liver (EASL). EASL Clinical practice guidelines: Autoimmune hepatitis. J Hepatol 2015;63:971-1004. https://doi.org/10.1016/j.jhep.2015.06.030.
Manns MP, Czaja AJ, Gorham JD, Krawitt EL, Mieli-Vergani G, Vergani D, et al. Diagnosis and management of autoimmune hepatitis. Hepatology 2010;51:2193-2213. https://doi.org/10.1002/hep.23584.
Covelli C, Sacchi D, Sarcognato S, Cazzagon N, Grillo F, Baciorri F, et al. Pathology of autoimmune hepatitis. Pathologica 2021;113:185-193. https://doi.org/10.32074/1591-951X-241.
Andrade RJ, Chalasani N, Björnsson ES, Suzuki A, Kullak-Ublick GA, Watkins PB, et al. Drug-induced liver injury. Nat Rev Dis Primers 2019;5:58. https://doi.org/10.1038/s41572-019-0105-0.
Björnsson ES. Epidemiology, predisposing factors, and outcomes of drug-induced liver injury. Clin Liver Dis 2020;24:1-10. https://doi.org/10.1016/j.cld.2019.08.002.
Cabrera-Rojas DL, Soto-Cardona J, Toro-Molina JL, Pérez-Cadavid JC, Marín-Zuluaga JI. Colestasis inducida por anabólicos: reporte de caso y revisión de la literatura. Rev Hepatol 2021;2:273-281. https://doi.org/10.52784/27112330.134.
Kleiner DE, Chalasani NP, Lee WM, Fontana RJ, Bonkovsky HL, Watkins PB, et al. Hepatic histological findings in suspected drug-induced liver injury: systematic evaluation and clinical associations. Hepatology 2014;59:661-670. https://doi.org/10.1002/hep.26709.
Di Tommaso L, Spadaccini M, Donadon M, Personeni N, Elamin A, Aghemo A, et al. Role of liver biopsy in hepatocellular carcinoma. World J Gastroenterol 2019;25:6041-6052. https://doi.org/10.3748/wjg.v25.i40.6041.
Procopet B, Berzigotti A. Diagnosis of cirrhosis and portal hypertension: imaging, non-invasive markers of fibrosis and liver biopsy. Gastroenterol Rep (Oxf) 2017;5:79-89. https://doi.org/10.1093/gastro/gox012.
Lo RC, Kim H. Histopathological evaluation of liver fibrosis and cirrhosis regression. Clin Mol Hepatol 2017;23:302-307. https://doi.org/10.3350/cmh.2017.0078.
Vyas M, Zhang X. Hepatocellular carcinoma: Role of pathology in the era of precision medicine. Clin Liver Dis 2020;24:591-610. https://doi.org/10.1016/j.cld.2020.07.010.
Strassburg CP. Hyperbilirubinemia syndromes (Gilbert-Meulengracht, Crigler-Najjar, Dubin-Johnson, and Rotor syndrome). Best Pract Res Clin Gastroenterol 2010;24:555-571. https://doi.org/10.1016/j.bpg.2010.07.007.
Squires JE, McKiernan P. Molecular mechanisms in pediatric cholestasis. Gastroenterol Clin North Am 2018;47:921-937. https://doi.org/10.1016/j.gtc.2018.07.014.
Romero FP. Will non-invasive testing replace liver biopsy in the diagnosis and follow-up of non-alcoholic steatohepatitis (NASH)? Rev Esp Enferm Dig 2009;101:521-527. https://doi.org/10.4321/s1130-01082009000800001.
Hernández-Osorio IC, Luján-Ramos MA. Aspectos relevantes de la enfermedad por hígado graso no alcohólico. Rev Hepatol 2021;2:310-324.
Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 1999;94:2467-2474. https://doi.org/10.1111/j.1572-0241.1999.01377.x.
Morantes-Rubiano JF, Pérez Cadavid JC, Restrepo-Gutiérrez JC, Muñoz-Maya O. Falla hepática subaguda secundaria a hepatotoxicidad severa por medicamentos: reporte de caso. Rev Hepatol 2020;1:165-175. https://doi.org/10.52784/27112330.124.
Srivastava A. Progressive familial intrahepatic cholestasis. J Clin Exp Hepatol 2014;4:25-36. https://doi.org/10.1016/j.jceh.2013.10.005.
Alburquerque-Miranda M, Vargas-Cárdenas G, Lozano-Miranda Z, Reyes-Mugruza T, Li-Torres W, Valdivia-Roldán M. Colestasis intrahepática benigna recurrente y su progresión a colestasis intrahepática familiar progresiva. Rev Gastroenterol Peru 2008;28:183-188.
Kumar P, Charaniya R, Ahuja A, Mittal S, Sahoo R. Benign recurrent intrahepatic cholestasis in a young adult. J Clin Diagn Res 2016;10:OD01-OD02. https://doi.org/10.7860/JCDR/2016/18917.7924.
Vij M, Rela M. Biliary atresia: pathology, etiology and pathogenesis. Future Sci OA 2020;6:Fso466. https://doi.org/10.2144/fsoa-2019-0153.
Morotti RA, Jain D. Pediatric cholestatic disorders: Approach to pathologic diagnosis. Surg Pathol Clin 2013;6:205-225. https://doi.org/10.1016/j.path.2013.03.001.
Tanaka A. Current understanding of primary biliary cholangitis. Clin Mol Hepatol 2021;27:1-21. https://doi.org/10.3350/cmh.2020.0028.
Prieto J, Banales JM, Medina JF. Primary biliary cholangitis: pathogenic mechanisms. Curr Opin Gastroenterol 2021;37:91-98. https://doi.org/10.1097/mog.0000000000000703.
Parés A. Primary biliary cholangitis. Med Clin 2018;151:242-249. https://doi.org/10.1016/j.medcli.2017.12.021.
Wiesner RH, LaRusso NF, Ludwig J, Dickson ER. Comparison of the clinicopathologic features of primary sclerosing cholangitis and primary biliary cirrhosis. Gastroenterology 1985;88:108-114. https://doi.org/10.1016/s0016-5085(85)80141-4.
Dyson JK, Beuers U, Jones DEJ, Lohse AW, Hudson M. Primary sclerosing cholangitis. Lancet 2018;391:2547-2559. https://doi.org/10.1016/s0140-6736(18)30300-3.
Downloads
Published
How to Cite
Issue
Section
License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Hepatología’s authorship policy is based on the criteria established by the International Committee of Medical Journal Editors (ICMJE) to credit a person for their work while assigning them responsibility for its publication.
| Article metrics | |
|---|---|
| Abstract views | |
| Galley vies | |
| PDF Views | |
| HTML views | |
| Other views | |















