Liver biopsies in pediatric patients—a histopathologicalreview of common entities
Main Article Content
Keywords
Biopsy; Indications; Liver; Management; Pediatric
Abstract
With the advent of sophisticated non-invasive assays and advanced radiologic techniques, there has been a significant evolution in the role of liver biopsy in the evaluation and management of hepatic diseases. Liver biopsy has a vital role in establishing the diagnosis, staging and prognostic evaluation of various pediatric liver diseases. It is an essential tool in deciding therapeutic management and treatment response. Liver biopsy when used in combination with clinical findings and other diagnostic modalities is useful in guiding treatment and predicting prognosis in the pediatric population. Here we discuss the indications of liver biopsy in various common pediatric liver diseases.
References
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[2] Dezsőfi A, Baumann U, Dhawan A, Durmaz O, Fischler B, Hadzic N, et al. Liver biopsy in children. Journal of Pediatric Gastroenterology and Nutrition. 2015; 60: 408–420.
[3] García-Compean D, Cortés C. Transjugular liver biopsy. An update. Annals of Hepatology. 2004; 3: 100–103.
[4] Srivastava A, Prasad D, Panda I, Yadav R, Jain M, Sarma MS, et al. Transjugular versus percutaneous liver biopsy in children: indication, success, yield, and complications. Journal of Pediatric Gastroenterology and Nutrition. 2020; 70: 417–422.
[5] Rockey DC, Caldwell SH, Goodman ZD, Nelson RC, Smith AD; American Association for the Study of Liver Diseases. Liver biopsy. Hepatology. 2009; 49: 1017–1044.
[6] Ranucci G, Della Corte C, Alberti D, Bondioni MP, Boroni G, Calvo PL, et al. Diagnostic approach to neonatal and infantile cholestasis: a position paper by the SIGENP liver disease working group. Digestive and Liver Disease. 2022; 54: 40–53.
[7] Feldman AG, Sokol RJ. Recent developments in diagnostics and treatment of neonatal cholestasis. Seminars in Pediatric Surgery. 2020; 29: 150945.
[8] Antala S, Taylor SA. Biliary atresia in children: update on disease mechanism, therapies, and patient outcomes. Clinics in Liver Disease. 2022; 26: 341–354.
[9] Nayak NC, Vasdev N. Neonatal cholestasis syndrome: identifying the disease from liver biopsy. Indian Pediatrics. 2002; 39: 421–425.
[10] Russo P, Magee JC, Boitnott J, Bove KE, Raghunathan T, Finegold M, et al.; Biliary Atresia Research Consortium. Design and validation of the biliary atresia research consortium histologic assessment system for cholestasis in infancy. Clinical Gastroenterology and Hepatology. 2011; 9: 357–362.e2.
[11] Patel KR. Biliary atresia and its mimics. Diagnostic Histopathology. 2023; 29: 52–66.
[12] Azar G, Beneck D, Lane B, Markowitz J, Daum F, Kahn E. Atypical morphologic presentation of biliary atresia and value of serial liver biopsies. Journal of Pediatric Gastroenterology and Nutrition. 2002; 34: 212–215.
[13] Ahmed ABM, Fagih MA, Bashir MS, Al-Hussaini AA. Role of percutaneous liver biopsy in infantile cholestasis: cohort from Arabs. BMC Gastroenterology. 2021; 21: 118.
[14] Lefkowitch JH. Childhood liver disease and metabolic disorders. Scheuer’s Liver Biopsy Interpretation. 2021; 19: 288–322.
[15] Giriyan S, Marathe A. Idiopathic neonatal hepatitis—a case report. Global Journal for Research Analysis. 2015; 4: 13–14.
[16] Buonpane CL, Ares GJ, Englert EG, Helenowski I, Cohran VC, Hunter CJ. Utility of liver biopsy in the evaluation of pediatric total parenteral nutrition cholestasis. The American Journal of Surgery. 2018; 216: 672–677.
[17] Feldman AG, Sokol RJ. Neonatal cholestasis: updates on diagnostics, therapeutics, and prevention. NeoReviews. 2021; 22: e819–e836.
[18] Naini BV, Lassman CR. Total parenteral nutrition therapy and liver injury: a histopathologic study with clinical correlation. Human Pathology. 2012; 43: 826–833.
[19] Gunaydin M, Bozkurter Cil AT. Progressive familial intrahepatic cholestasis: diagnosis, management, and treatment. Hepatic Medicine. 2018; 10: 95–104.
[20] Clayton RJ, Iber FL, Ruebner BH, Mckusick VA. Byler disease. Fatal familial intrahepatic cholestasis in an Amish kindred. American Journal of Diseases of Children. 1969; 117: 112–124.
[21] Srivastava A. Progressive familial intrahepatic cholestasis. Journal of Clinical and Experimental Hepatology. 2014; 4: 25–36.
[22] Evason K, Bove KE, Finegold MJ, Knisely AS, Rhee S, Rosenthal P, et al. Morphologic findings in progressive familial intrahepatic cholestasis 2 (PFIC2): correlation with genetic and immunohistochemical studies. The American Journal of Surgical Pathology. 2011; 35: 687–696.
[23] Ovchinsky N, Moreira RK, Lefkowitch JH, Lavine JE. Liver biopsy in modern clinical practice: a pediatric point-of-view. Advances in Anatomic Pathology. 2012; 19: 250–262.
[24] Alissa FT, Jaffe R, Shneider BL. Update on progressive familial intrahepatic cholestasis. Journal of Pediatric Gastroenterology and Nutrition. 2008; 46: 241–252.
[25] Emerick KM, Elias MS, Melin-Aldana H, Strautnieks S, Thompson RJ, Bull LN, et al. Bile composition in Alagille Syndrome and PFIC patients having partial external biliary diversion. BMC Gastroenterology. 2008; 8: 47.
[26] Melter M, Rodeck B, Kardorff R, Hoyer PF, Petersen C, Ballauff A, et al. Progressive familial intrahepatic cholestasis: partial biliary diversion normalizes serum lipids and improves growth in noncirrhotic patients. The American Journal of Gastroenterology. 2000; 95: 3522–3528.
[27] Kaliciński PJ, Ismail H, Jankowska I, Kamiński A, Pawłowska J, Drewniak T, et al. Surgical treatment of progressive familial intrahepatic cholestasis: comparison of partial external biliary diversion and ileal bypass. European Journal of Pediatric Surgery. 2003; 13: 307–311.
[28] Subramaniam P, Knisely A, Portmann B, Qureshi SA, Aclimandos WA, Karani JB, et al. Diagnosis of Alagille syndrome—25 years of experience at King’s College Hospital. Journal of Pediatric Gastroenterology and Nutrition. 2011; 52: 84–89.
[29] Francavilla R, Castellaneta SP, Hadzic N, Chambers SM, Portmann B, Tung J, et al. Prognosis of alpha-1-antitrypsin deficiency-related liver disease in the era of paediatric liver transplantation. Journal of Hepatology. 2000; 32: 986–992.
[30] Adar T, Ilan Y, Elstein D, Zimran A. Liver involvement in Gaucher disease—Review and clinical approach. Blood Cells, Molecules & Diseases. 2018; 68: 66–73.
[31] Thurberg BL, Wasserstein MP, Schiano T, O’Brien F, Richards S, Cox GF, et al. Liver and skin histopathology in adults with acid sphingomyelinase deficiency (Niemann-Pick disease type B). The American Journal of Surgical Pathology. 2012; 36: 1234–1246.
[32] Vélez Pinos PJ, Saavedra Palacios MS, Colina Arteaga PA, Arevalo Cordova TD. Niemann-pick disease: a case report and literature review. Cureus. 2023; 15: e33534.
[33] Cope-Yokoyama S, Finegold MJ, Sturniolo GC, Kim K, Mescoli C, Rugge M, et al. Wilson disease: histopathological correlations with treatment on follow-up liver biopsies. World Journal of Gastroenterology. 2010; 16: 1487–1494.
[34] Ferenci P, Caca K, Loudianos G, Mieli-Vergani G, Tanner S, Sternlieb I, et al. Diagnosis and phenotypic classification of Wilson disease. Liver International. 2003; 23: 139–142.
[35] 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 Transplantation. 2005; 11: 441–448.
[36] Boëlle PY, Debray D, Guillot L, Clement A, Corvol H; French CF Modifier Gene Study Investigators. Cystic fibrosis liver disease: outcomes and risk factors in a large cohort of French patients. Hepatology. 2019; 69: 1648–1656.
[37] Betapudi B, Aleem A, Kothadia JP. Cystic fibrosis and liver disease. StatPearls Publishing: Treasure Island (FL). 2025.
[38] Squires RH III, Shneider BL, Bucuvalas J, Alonso E, Sokol RJ, Narkewicz MR, et al. Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group. The Journal of Pediatrics. 2006; 148: 652–658.
[39] Lee WM, Squires RH III, Nyberg SL, Doo E, Hoofnagle JH. Acute liver failure: summary of a workshop. Hepatology. 2008; 47: 1401–1415.
[40] Di Giorgio A, Gamba S, Sansotta N, Nicastro E, Colledan M, D’Antiga L. Identifying the aetiology of acute liver failure is crucial to impact positively on outcome. Children. 2023; 10: 473.
[41] Miraglia R, Luca A, Gruttadauria S, Minervini MI, Vizzini G, Arcadipane A, et al. Contribution of transjugular liver biopsy in patients with the clinical presentation of acute liver failure. Cardiovascular and Interventional Radiology. 2006; 29: 1008–1010.
[42] Habdank K, Restrepo R, Ng V, Connolly BL, Temple MJ, Amaral J, et al. Combined sonographic and fluoroscopic guidance during transjugular hepatic biopsies performed in children: a retrospective study of 74 biopsies. American Journal of Roentgenology. 2003; 180: 1393–1398.
[43] Vajro P, Lenta S, Socha P, Dhawan A, McKiernan P, Baumann U, et al. Diagnosis of nonalcoholic fatty liver disease in children and adolescents: position paper of the ESPGHAN Hepatology Committee. Journal of Pediatric Gastroenterology and Nutrition. 2012; 54: 700–713.
[44] Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018; 67: 328–357.
[45] Hunter AK, Lin HC. Review of clinical guidelines in the diagnosis of pediatric nonalcoholic fatty liver disease. Clinical Liver Disease. 2021; 18: 40–44.
[46] Lubrecht JW, van Giesen GHJ, Jańczyk W, Zavhorodnia O, Zavhorodnia N, Socha P, et al.; ESPGHAN Fatty Liver Special Interest Group. Pediatricians’ practices and knowledge of metabolic dysfunction-associated steatotic liver disease: an international survey. Journal of Pediatric Gastroenterology and Nutrition. 2024; 78: 524–533.
[47] Vos MB, Abrams SH, Barlow SE, Caprio S, Daniels SR, Kohli R, 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). Journal of Pediatric Gastroenterology and Nutrition. 2017; 64: 319–334.
[48] Sakhuja P, Goyal S. Autoimmune hepatitis: from evolution to current status—a pathologist’s perspective. Diagnostics. 2024; 14: 210.
[49] Alvarez F, Berg PA, Bianchi FB, Bianchi L, Burroughs AK, Cancado EL, et al. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. Journal of Hepatology. 1999; 31: 929–938.
[50] Nastasio S, Mosca A, Alterio T, Sciveres M, Maggiore G. Juvenile autoimmune hepatitis: recent advances in diagnosis, management and long-term outcome. Diagnostics. 2023; 13: 2753.
[51] Lohse AW, Sebode M, Jørgensen MH, Ytting H, Karlsen TH, Kelly D, et al.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER); International Autoimmune Hepatitis Group (IAIHG). Second-line and third-line therapy for autoimmune hepatitis: a position statement from the European Reference Network on Hepatological Diseases and the International Autoimmune Hepatitis Group. Journal of Hepatology. 2020; 73: 1496–1506.
[52] Dave M, Elmunzer BJ, Dwamena BA, Higgins PD. Primary sclerosing cholangitis: meta-analysis of diagnostic performance of MR cholangiopancreatography. Radiology. 2010; 256: 387–396.
[53] Harrison RF, Hubscher SG. The spectrum of bile duct lesions in end-stage primary sclerosing cholangitis. Histopathology. 1991; 19: 321–327.
[54] Fuchs Y, Valentino PL. Natural history and prognosis of pediatric PSC with updates on management. Clinical Liver Disease. 2023; 21: 47–51.
[55] Rabiee A, Silveira MG. Primary sclerosing cholangitis. Translational Gastroenterology and Hepatology. 2021; 6: 29.
[56] Gregorio GV, Portmann B, Karani J, Harrison P, Donaldson PT, Vergani D, et al. Autoimmune hepatitis/sclerosing cholangitis overlap syndrome in childhood: a 16-year prospective study. Hepatology. 2001; 33: 544–553.
[57] Jonas MM, Mizerski J, Badia IB, Areias JA, Schwarz KB, Little NR, et al.; International Pediatric Lamivudine Investigator Group. Clinical trial of lamivudine in children with chronic hepatitis B. The New England Journal of Medicine. 2002; 346: 1706–1713.
[58] Jara P, Bortolotti F. Interferon-alpha treatment of chronic hepatitis B in childhood: a consensus advice based on experience in European children. Journal of Pediatric Gastroenterology and Nutrition. 1999; 29: 163–170.
[59] Guido M, Bortolotti F. Chronic viral hepatitis in children: any role for the pathologist? Gut. 2008; 57: 873–877.
[60] Chowdhury AB, Mehta KJ. Liver biopsy for assessment of chronic liver diseases: a synopsis. Clinical and Experimental Medicine. 2023; 23: 273–285.
[61] Paya CV, Holley KE, Wiesner RH, Balasubramaniam K, Smith TF, Espy MJ, et al. Early diagnosis of cytomegalovirus hepatitis in liver transplant recipients: role of immunostaining, DNA hybridization and culture of hepatic tissue. Hepatology. 1990; 12: 119–126.
[62] Koch DG, Christiansen L, Lazarchick J, Stuart R, Willner IR, Reuben A. Posttransplantation lymphoproliferative disorder--the great mimic in liver transplantation: appraisal of the clinicopathologic spectrum and the role of Epstein-Barr virus. Liver Transplantation. 2007; 13: 904–912.
[63] Barkholt L, Reinholt FP, Teramoto N, Enbom M, Dahl H, Linde A. Polymerase chain reaction and in situ hybridization of Epstein-Barr virus in liver biopsy specimens facilitate the diagnosis of EBV hepatitis after liver transplantation. Transplant International. 1998; 11: 336–344.
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Jun 20, 2025
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Liver biopsies in pediatric patients—a histopathologicalreview of common entities. (2025). Journal of Renal and Hepatic Disorders, 9(1), 1-11. https://doi.org/10.63268/jrenhp.v9i1.198
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Review Hepatology
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Author Biography
Maria Kamal, Heartland Pathology Laboratory, Wichita, KS 67226, USA
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