Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Hepatic manifestations of sickle cell disease

Subhas Banerjee, MD
Michael R DeBaun, MD, MPH
Section Editors
Sanjiv Chopra, MD, MACP
Stanley L Schrier, MD
Deputy Editor
Kristen M Robson, MD, MBA, FACG


Sickle cell disease (SCD) encompasses a group of hemoglobinopathies characterized by a single amino acid substitution in the ß-globin chain. The most frequently occurring form of SCD is sickle cell anemia (HbSS), followed by HbSC and HbSß-thalassemia. In SCD the majority of the hemoglobin (greater than 50 percent) is hemoglobin S. In the United States, 6 to 10 percent of African-American newborns have sickle cell trait (HbSA), and approximately 0.2 percent have sickle cell anemia (HbSS) [1]. Sickle cell trait is not considered SCD. (See "Introduction to hemoglobin mutations".)

The liver can be affected by a number of complications due to the disease itself and its treatment [2-4]. In addition to the vascular complications from the sickling process, patients with SCD have often received multiple transfusions, placing them at risk for viral hepatitis, iron overload, and (combined with the effects of chronic hemolysis) the development of pigment gallstones, all of which may contribute to the development of liver disease. (See "Epidemiology and transmission of hepatitis C virus infection", section on 'Blood transfusion' and "Epidemiology, transmission, and prevention of hepatitis B virus infection", section on 'Transfusion' and "Red blood cell transfusion in sickle cell disease", section on 'Excessive iron stores'.)

The term "sickle cell hepatopathy" has sometimes been used to reflect the overlapping causes of liver dysfunction in these patients. Sickle cell hepatopathy occurs predominantly in patients with homozygous sickle cell anemia, and to a lesser extent in patients with HbSC disease or HbSß-thalassemia.

This topic will review the hepatic manifestation of SCD. Other issues related to SCD are discussed elsewhere. (See "Overview of the clinical manifestations of sickle cell disease" and "Overview of the management and prognosis of sickle cell disease".)


The overall incidence of liver disease in patients with sickle cell disease (SCD) has not been well established. The major risk factor for liver disease in patients with SCD is receiving multiple blood transfusions, which is associated with infection (hepatitis B and C) and excessive iron stores.

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Jan 26, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Castro O, Rana SR, Bang KM, Scott RB. Age and prevalence of sickle-cell trait in a large ambulatory population. Genet Epidemiol 1987; 4:307.
  2. Banerjee S, Owen C, Chopra S. Sickle cell hepatopathy. Hepatology 2001; 33:1021.
  3. Berry PA, Cross TJ, Thein SL, et al. Hepatic dysfunction in sickle cell disease: a new system of classification based on global assessment. Clin Gastroenterol Hepatol 2007; 5:1469.
  4. Ebert EC, Nagar M, Hagspiel KD. Gastrointestinal and hepatic complications of sickle cell disease. Clin Gastroenterol Hepatol 2010; 8:483.
  5. Johnson CS, Omata M, Tong MJ, et al. Liver involvement in sickle cell disease. Medicine (Baltimore) 1985; 64:349.
  6. Bauer TW, Moore GW, Hutchins GM. The liver in sickle cell disease. A clinicopathologic study of 70 patients. Am J Med 1980; 69:833.
  7. SONG YS. Hepatic lesions in sickle cell anemia. Am J Pathol 1957; 33:331.
  8. GREEN TW, CONLEY CL, BERTHRONG M. [The liver in sickle cell anemia]. Bull Johns Hopkins Hosp 1953; 92:99.
  9. Mills LR, Mwakyusa D, Milner PF. Histopathologic features of liver biopsy specimens in sickle cell disease. Arch Pathol Lab Med 1988; 112:290.
  10. Sheehy TW. Sickle cell hepatopathy. South Med J 1977; 70:533.
  11. Brody JI, Ryan WN, Haidar MA. Serum alkaline phosphatase isoenzymes in sickle cell anemia. JAMA 1975; 232:738.
  12. Mohamed AO, Jansson A, Ronquist G. Increased activity of 5' nucleotidase in serum of patients with sickle cell anaemia. Scand J Clin Lab Invest 1993; 53:701.
  13. DeVault KR, Friedman LS, Westerberg S, et al. Hepatitis C in sickle cell anemia. J Clin Gastroenterol 1994; 18:206.
  14. Karayalcin G, Lanzkowsky P. Plasma protein C levels in children with sickle cell disease. Am J Pediatr Hematol Oncol 1989; 11:320.
  15. Tam DA. Protein C and protein S activity in sickle cell disease and stroke. J Child Neurol 1997; 12:19.
  16. Wright JG, Malia R, Cooper P, et al. Protein C and protein S in homozygous sickle cell disease: does hepatic dysfunction contribute to low levels? Br J Haematol 1997; 98:627.
  17. Karayalcin G, Lanzkowsky P, Kazi AB. Zinc deficiency in children with sickle cell disease. Am J Pediatr Hematol Oncol 1979; 1:283.
  18. Yuzbasiyan-Gurkan VA, Brewer GJ, Vander AJ, et al. Net renal tubular reabsorption of zinc in healthy man and impaired handling in sickle cell anemia. Am J Hematol 1989; 31:87.
  19. Silliman CC, Peterson VM, Mellman DL, et al. Iron chelation by deferoxamine in sickle cell patients with severe transfusion-induced hemosiderosis: a randomized, double-blind study of the dose-response relationship. J Lab Clin Med 1993; 122:48.
  20. Leonard MB, Zemel BS, Kawchak DA, et al. Plasma zinc status, growth, and maturation in children with sickle cell disease. J Pediatr 1998; 132:467.
  21. Rabbani P, Prasad AS. Plasma ammonia and liver ornithine transcarbamoylase activity in zinc-deficient rats. Am J Physiol 1978; 235:E203.
  22. Brewer GJ, Hill GM, Dick RD, et al. Interactions of trace elements: clinical significance. J Am Coll Nutr 1985; 4:33.
  23. Prasad AS, Rabbani P, Warth JA. Effect of zinc on hyperammonemia in sickle cell anemia subjects. Am J Hematol 1979; 7:323.
  24. Prasad AS, Beck FW, Kaplan J, et al. Effect of zinc supplementation on incidence of infections and hospital admissions in sickle cell disease (SCD). Am J Hematol 1999; 61:194.
  25. Gupta VL, Chaubey BS. Efficacy of zinc therapy in prevention of crisis in sickle cell anemia: a double blind, randomized controlled clinical trial. J Assoc Physicians India 1995; 43:467.
  26. Brewer GJ, Hill GM, Prasad AS, Cossack ZT. Biological roles of ionic zinc. Prog Clin Biol Res 1983; 129:35.
  27. Zakaria N, Knisely A, Portmann B, et al. Acute sickle cell hepatopathy represents a potential contraindication for percutaneous liver biopsy. Blood 2003; 101:101.
  28. Villeneuve JP, Bilodeau M, Lepage R, et al. Variability in hepatic iron concentration measurement from needle-biopsy specimens. J Hepatol 1996; 25:172.
  29. Rosenblate HJ, Eisenstein R, Holmes AW. The liver in sickle cell anemia. A clinical-pathologic study. Arch Pathol 1970; 90:235.
  30. Diggs LW, Ching RE. Pathology of sickle cell anemia. South Med J 1934; 27:839.
  31. Omata M, Johnson CS, Tong M, Tatter D. Pathological spectrum of liver diseases in sickle cell disease. Dig Dis Sci 1986; 31:247.
  32. Shao SH, Orringer EP. Sickle cell intrahepatic cholestasis: approach to a difficult problem. Am J Gastroenterol 1995; 90:2048.
  33. Charlotte F, Bachir D, Nénert M, et al. Vascular lesions of the liver in sickle cell disease. A clinicopathological study in 26 living patients. Arch Pathol Lab Med 1995; 119:46.
  34. Aken'ova YA, Olasode BJ, Ogunbiyi JO, Thomas JO. Hepatobiliary changes in Nigerians with sickle cell anaemia. Ann Trop Med Parasitol 1993; 87:603.
  35. Barrett-Connor E. Sickle cell disease and viral hepatitis. Ann Intern Med 1968; 69:517.
  36. Wolfe JL, Anders RA, Reddoch S, et al. Longitudinal changes in liver fibrosis in children with sickle cell disease undergoing chronic transfusion therapy. Acta Gastroenterol Belg 2012; 75:419.
  37. Hankins JS, Smeltzer MP, McCarville MB, et al. Patterns of liver iron accumulation in patients with sickle cell disease and thalassemia with iron overload. Eur J Haematol 2010; 85:51.
  38. Ghugre NR, Wood JC. Relaxivity-iron calibration in hepatic iron overload: probing underlying biophysical mechanisms using a Monte Carlo model. Magn Reson Med 2011; 65:837.
  39. Flyer MA, Haller JO, Sundaram R. Transfusional hemosiderosis in sickle cell anemia: another cause of an echogenic pancreas. Pediatr Radiol 1993; 23:140.
  40. Siegelman ES, Outwater E, Hanau CA, et al. Abdominal iron distribution in sickle cell disease: MR findings in transfusion and nontransfusion dependent patients. J Comput Assist Tomogr 1994; 18:63.
  41. Adler DD, Glazer GM, Aisen AM. MRI of the spleen: normal appearance and findings in sickle-cell anemia. AJR Am J Roentgenol 1986; 147:843.
  42. Diggs LW. Sickle cell crises. Am J Clin Pathol 1965; 44:1.
  43. Schubert TT. Hepatobiliary system in sickle cell disease. Gastroenterology 1986; 90:2013.
  44. Saltzman JR, Johnston DE. Sickle cell crisis and cocaine hepatotoxicity. Am J Gastroenterol 1992; 87:1661.
  45. Hatton CS, Bunch C, Weatherall DJ. Hepatic sequestration in sickle cell anaemia. Br Med J (Clin Res Ed) 1985; 290:744.
  46. Hernández P, Dorticós E, Espinosa E, et al. Clinical features of hepatic sequestration in sickle cell anaemia. Haematologia (Budap) 1989; 22:169.
  47. Yawn BP, Buchanan GR, Afenyi-Annan AN, et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA 2014; 312:1033.
  48. http://www.nhlbi.nih.gov/health-pro/guidelines/current/management-sickle-cell-disease.htm (Accessed on September 30, 2014).
  49. Lee ES, Chu PC. Reverse sequestration in a case of sickle crisis. Postgrad Med J 1996; 72:487.
  50. Stéphan JL, Merpit-Gonon E, Richard O, et al. Fulminant liver failure in a 12-year-old girl with sickle cell anaemia: favourable outcome after exchange transfusions. Eur J Pediatr 1995; 154:469.
  52. Sheehy TW, Law DE, Wade BH. Exchange transfusion for sickle cell intrahepatic cholestasis. Arch Intern Med 1980; 140:1364.
  54. Svarch E, González A, Villaescusa R, Basanta P. Plasma exchange for acute cholestasis in homozygous sickle cell disease. Haematologia (Budap) 1986; 19:49.
  55. Morrow JD, McKenzie SW. Survival after intrahepatic cholestasis associated with sickle cell disease. J Tenn Med Assoc 1986; 79:199.
  56. Betrosian A, Balla M, Kafiri G, et al. Reversal of liver failure in sickle cell vaso-occlusive crisis. Am J Med Sci 1996; 311:292.
  57. Khan MA, Kerner JA. Reversal of hepatic and renal failure from sickle cell intrahepatic cholestasis. Dig Dis Sci 2011; 56:1634.
  58. Buchanan GR, Glader BE. Benign course of extreme hyperbilirubinemia in sickle cell anemia: analysis of six cases. J Pediatr 1977; 91:21.
  59. O'Callaghan A, O'Brien SG, Ninkovic M, et al. Chronic intrahepatic cholestasis in sickle cell disease requiring exchange transfusion. Gut 1995; 37:144.
  60. Rennels MB, Dunne MG, Grossman NJ, Schwartz AD. Cholelithiasis in patients with major sickle hemoglobinopathies. Am J Dis Child 1984; 138:66.
  61. Adam S, Jonassaint J, Kruger H, et al. Surgical and obstetric outcomes in adults with sickle cell disease. Am J Med 2008; 121:916.
  62. Webb DK, Darby JS, Dunn DT, et al. Gall stones in Jamaican children with homozygous sickle cell disease. Arch Dis Child 1989; 64:693.
  63. Sarnaik S, Slovis TL, Corbett DP, et al. Incidence of cholelithiasis in sickle cell anemia using the ultrasonic gray-scale technique. J Pediatr 1980; 96:1005.
  64. Walker TM, Hambleton IR, Serjeant GR. Gallstones in sickle cell disease: observations from The Jamaican Cohort study. J Pediatr 2000; 136:80.
  65. Bond LR, Hatty SR, Horn ME, et al. Gall stones in sickle cell disease in the United Kingdom. Br Med J (Clin Res Ed) 1987; 295:234.
  66. Irizarry K, Rossbach HC, Ignacio JR, et al. Sickle cell intrahepatic cholestasis with cholelithiasis. Pediatr Hematol Oncol 2006; 23:95.
  67. D'Alonzo WA Jr, Heyman S. Biliary scintigraphy in children with sickle cell anemia and acute abdominal pain. Pediatr Radiol 1985; 15:395.
  68. Malone BS, Werlin SL. Cholecystectomy and cholelithiasis in sickle cell anemia. Am J Dis Child 1988; 142:799.
  69. Vichinsky EP, Haberkern CM, Neumayr L, et al. A comparison of conservative and aggressive transfusion regimens in the perioperative management of sickle cell disease. The Preoperative Transfusion in Sickle Cell Disease Study Group. N Engl J Med 1995; 333:206.
  70. Goers T, Panepinto J, Debaun M, et al. Laparoscopic versus open abdominal surgery in children with sickle cell disease is associated with a shorter hospital stay. Pediatr Blood Cancer 2008; 50:603.
  71. Porter JB, Huehns ER. Transfusion and exchange transfusion in sickle cell anaemias, with particular reference to iron metabolism. Acta Haematol 1987; 78:198.
  72. Brownell A, Lowson S, Brozović M. Serum ferritin concentration in sickle cell crisis. J Clin Pathol 1986; 39:253.
  73. Brittenham GM, Cohen AR, McLaren CE, et al. Hepatic iron stores and plasma ferritin concentration in patients with sickle cell anemia and thalassemia major. Am J Hematol 1993; 42:81.
  74. Pippard MJ. Iron overload and iron chelation therapy in thalassaemia and sickle cell haemoglobinopathies. Acta Haematol 1987; 78:206.
  75. Karam LB, Disco D, Jackson SM, et al. Liver biopsy results in patients with sickle cell disease on chronic transfusions: poor correlation with ferritin levels. Pediatr Blood Cancer 2008; 50:62.
  76. Harmatz P, Butensky E, Quirolo K, et al. Severity of iron overload in patients with sickle cell disease receiving chronic red blood cell transfusion therapy. Blood 2000; 96:76.
  77. Laulan S, Bernard JF, Boivin P. [Systematic blood transfusions in adult homozygote sickle-cell anemia. Study of 11 cases followed for 5 to 10 years]. Presse Med 1990; 19:785.
  78. Yohannan MD, Arif M, Ramia S. Aetiology of icteric hepatitis and fulminant hepatic failure in children and the possible predisposition to hepatic failure by sickle cell disease. Acta Paediatr Scand 1990; 79:201.
  79. Hasan MF, Marsh F, Posner G, et al. Chronic hepatitis C in patients with sickle cell disease. Am J Gastroenterol 1996; 91:1204.
  80. Mok Q, Underhill G, Wonke B, et al. Intradermal hepatitis B vaccine in thalassaemia and sickle cell disease. Arch Dis Child 1989; 64:535.
  81. Jeannel D, Fretz C, Traore Y, et al. Evidence for high genetic diversity and long-term endemicity of hepatitis C virus genotypes 1 and 2 in West Africa. J Med Virol 1998; 55:92.
  82. al-Fawaz I, Ramia S. Decline in hepatitis B infection in sickle cell anaemia and beta thalassaemia major. Arch Dis Child 1993; 69:594.
  83. Issa H. Safety of pegylated interferon and ribavirin therapy for chronic hepatitis C in patients with sickle cell anemia. World J Hepatol 2010; 2:180.
  84. Gauthier N, Cornud F, Vissuzaine C. Liver infarction in sickle cell disease. AJR Am J Roentgenol 1985; 144:1089.
  85. Chong SK, Dick MC, Howard ER, Mowat AP. Liver abscess as an unusual complication in sickle cell anemia. J Pediatr Gastroenterol Nutr 1993; 16:221.
  86. Brittain HP, De la Torre A, Willey EN. A case of sickle cell disease with an abscess arising in an infarct of the liver. Ann Intern Med 1966; 65:560.
  87. Lama M. Hepatic abscess in sickle cell anaemia: a rare manifestation. Arch Dis Child 1993; 69:242.
  88. Shulman ST, Beem MO. An unique presentation of sickle cell disease: pyogenic hepatic abscess. Pediatrics 1971; 47:1019.
  89. Sty JR. Ultrasonography: hepatic vein thrombosis in sickle cell anemia. Am J Pediatr Hematol Oncol 1982; 4:213.
  90. Attal HC, Gupta VL, Salkar HR. Budd-Chiari syndrome due to inferior vena cava obstruction in sickle cell trait. J Assoc Physicians India 1984; 32:526.
  91. el Younis CM, Min AD, Fiel MI, et al. Autoimmune hepatitis in a patient with sickle cell disease. Am J Gastroenterol 1996; 91:1016.
  92. Chuang E, Ruchelli E, Mulberg AE. Autoimmune liver disease and sickle cell anemia in children: a report of three cases. J Pediatr Hematol Oncol 1997; 19:159.
  93. Markowitz RI, Harcke HT, Ritchie WG, Huff DS. Focal nodular hyperplasia of the liver in a child with sickle cell anemia. AJR Am J Roentgenol 1980; 134:594.
  94. Heaton ND, Pain J, Cowan NC, et al. Focal nodular hyperplasia of the liver: a link with sickle cell disease? Arch Dis Child 1991; 66:1073.
  95. Wong WS, Sherman NE, Moss AA. Malignant histiocytosis in a patient with sickle cell anemia: CT findings. J Comput Assist Tomogr 1983; 7:908.
  96. Arnold KE, Char G, Serjeant GR. Portal vein thrombosis in a child with homozygous sickle-cell disease. West Indian Med J 1993; 42:27.
  97. Alexanian R, Nadell J. Oxymetholone treatment for sickle cell anemia. Blood 1975; 45:769.
  98. Charache S, Terrin ML, Moore RD, et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med 1995; 332:1317.
  99. Kinney TR, Helms RW, O'Branski EE, et al. Safety of hydroxyurea in children with sickle cell anemia: results of the HUG-KIDS study, a phase I/II trial. Pediatric Hydroxyurea Group. Blood 1999; 94:1550.
  100. Koren A, Segal-Kupershmit D, Zalman L, et al. Effect of hydroxyurea in sickle cell anemia: a clinical trial in children and teenagers with severe sickle cell anemia and sickle cell beta-thalassemia. Pediatr Hematol Oncol 1999; 16:221.
  101. de Montalembert M, Belloy M, Bernaudin F, et al. Three-year follow-up of hydroxyurea treatment in severely ill children with sickle cell disease. The French Study Group on Sickle Cell Disease. J Pediatr Hematol Oncol 1997; 19:313.
  102. Saleh AW Jr, Velvis HJ, Gu LH, et al. Hydroxyurea therapy in sickle cell anemia patients in Curaçao, The Netherlands Antilles. Acta Haematol 1997; 98:125.
  103. Claster S, Vichinsky E. First report of reversal of organ dysfunction in sickle cell anemia by the use of hydroxyurea: splenic regeneration. Blood 1996; 88:1951.
  104. Kindscher JD, Laurin J, Delcore R, Forster J. Liver transplantation in a patient with sickle cell anemia. Transplantation 1995; 60:762.
  105. Lang T, Berquist WE, So SK, et al. Liver transplantation in a child with sickle cell anemia. Transplantation 1995; 59:1490.
  106. Lerut JP, Claeys N, Laterre PF, et al. Hepatic sickling: an unusual cause of liver allograft dysfunction. Transplantation 1999; 67:65.
  107. Emre S, Schwartz ME, Shneider B, et al. Living related liver transplantation for acute liver failure in children. Liver Transpl Surg 1999; 5:161.
  108. Mekeel KL, Langham MR Jr, Gonzalez-Peralta R, et al. Liver transplantation in children with sickle-cell disease. Liver Transpl 2007; 13:505.