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Diagnosis of hepatic sinusoidal obstruction syndrome (veno-occlusive disease) following hematopoietic cell transplantation

Authors
Robert S Negrin, MD
Peter A L Bonis, MD
Section Editor
Nelson J Chao, MD
Deputy Editor
Alan G Rosmarin, MD

INTRODUCTION

Hepatic sinusoidal obstruction syndrome (SOS), previously termed hepatic veno-occlusive disease (VOD), is characterized by hepatomegaly, right upper quadrant pain, jaundice, and ascites, most often occurring in patients undergoing hematopoietic cell transplantation (HCT) and less commonly following the use of chemotherapeutic agents in non-transplant settings, ingestion of alkaloid toxins, after high dose radiation therapy, or liver transplantation. The disease resembles the Budd-Chiari syndrome clinically; however, hepatic venous outflow obstruction in SOS is due to occlusion of the terminal hepatic venules and hepatic sinusoids rather than the hepatic veins and inferior vena cava.

The pathogenesis, clinical features, and diagnosis of SOS following HCT will be reviewed here. The prevention and treatment of this disorder are discussed separately. (See "Treatment and prevention of hepatic sinusoidal obstruction syndrome following hematopoietic cell transplantation".)

The term "hematopoietic cell transplantation" (HCT) will be used throughout this review as a general term to cover transplantation of progenitor cells from any source (eg, bone marrow, peripheral blood, cord blood). Otherwise, the source of such cells will be specified (eg, autologous peripheral blood progenitor cell transplantation). (See "Sources of hematopoietic stem cells".)

PATHOGENESIS

Hepatic sinusoidal obstruction syndrome (SOS) typically occurs in the context of hematopoietic cell transplantation (HCT). However, it may also be induced by the ingestion of pyrrolizidine alkaloids, usually from herbal sources (such as bush tea and other herbal teas) [1]; high dose radiation therapy to the liver (usually exceeding 30 Gy) without cytoreductive chemotherapy [2,3]; radioembolization of liver tumors [4]; and after liver transplantation [5,6]. (See "Hepatotoxicity due to herbal medications and dietary supplements".)

Regardless of the cause, SOS is thought to begin with injury to the hepatic venous endothelium. The observation that preexisting liver disease increases the risk of developing SOS provides some insight into the pathogenesis of this disorder. Preexisting liver disease may impair metabolism of drugs, and thus predispose to endothelial cell injury. In addition, patients with chronic hepatitis may have abnormalities in hepatic endothelial cells that could make them more susceptible to the cytoreductive regimen. Endothelial cells in patients with hepatitis may abnormally express adhesion molecules and procoagulant factors [7-9].

                   

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Literature review current through: Nov 2016. | This topic last updated: Wed Sep 14 00:00:00 GMT+00:00 2016.
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References
Top
  1. Brown AC. Liver toxicity related to herbs and dietary supplements: Online table of case reports. Part 3 of 6. Food Chem Toxicol 2016.
  2. Willemart S, Nicaise N, Struyven J, van Gansbeke D. Acute radiation-induced hepatic injury: evaluation by triphasic contrast enhanced helical CT. Br J Radiol 2000; 73:544.
  3. Sempoux C, Horsmans Y, Geubel A, et al. Severe radiation-induced liver disease following localized radiation therapy for biliopancreatic carcinoma: activation of hepatic stellate cells as an early event. Hepatology 1997; 26:128.
  4. Sangro B, Gil-Alzugaray B, Rodriguez J, et al. Liver disease induced by radioembolization of liver tumors: description and possible risk factors. Cancer 2008; 112:1538.
  5. Sebagh M, Debette M, Samuel D, et al. "Silent" presentation of veno-occlusive disease after liver transplantation as part of the process of cellular rejection with endothelial predilection. Hepatology 1999; 30:1144.
  6. Nakazawa Y, Chisuwa H, Mita A, et al. Life-threatening veno-occlusive disease after living-related liver transplantation. Transplantation 2003; 75:727.
  7. Zeniya M, Fukata H, Toda G. Thrombomodulin expression of sinusoidal endothelial cells in chronic viral hepatitis. J Gastroenterol Hepatol 1995; 10 Suppl 1:S77.
  8. Scoazec JY, Feldmann G. In situ immunophenotyping study of endothelial cells of the human hepatic sinusoid: results and functional implications. Hepatology 1991; 14:789.
  9. Volpes R, van den Oord JJ, Desmet VJ. Distribution of the VLA family of integrins in normal and pathological human liver tissue. Gastroenterology 1991; 101:200.
  10. McDonald GB, Sharma P, Matthews DE, et al. Venocclusive disease of the liver after bone marrow transplantation: diagnosis, incidence, and predisposing factors. Hepatology 1984; 4:116.
  11. Shulman HM, Gown AM, Nugent DJ. Hepatic veno-occlusive disease after bone marrow transplantation. Immunohistochemical identification of the material within occluded central venules. Am J Pathol 1987; 127:549.
  12. Shulman HM, Fisher LB, Schoch HG, et al. Veno-occlusive disease of the liver after marrow transplantation: histological correlates of clinical signs and symptoms. Hepatology 1994; 19:1171.
  13. Tabbara IA, Ghazal CD, Ghazal HH. Early drop in protein C and antithrombin III is a predictor for the development of venoocclusive disease in patients undergoing hematopoietic stem cell transplantation. J Hematother 1996; 5:79.
  14. Salat C, Holler E, Kolb HJ, et al. Plasminogen activator inhibitor-1 confirms the diagnosis of hepatic veno-occlusive disease in patients with hyperbilirubinemia after bone marrow transplantation. Blood 1997; 89:2184.
  15. Faioni EM, Krachmalnicoff A, Bearman SI, et al. Naturally occurring anticoagulants and bone marrow transplantation: plasma protein C predicts the development of venocclusive disease of the liver. Blood 1993; 81:3458.
  16. Scrobohaci ML, Drouet L, Monem-Mansi A, et al. Liver veno-occlusive disease after bone marrow transplantation changes in coagulation parameters and endothelial markers. Thromb Res 1991; 63:509.
  17. Iguchi A, Kobayashi R, Kaneda M, Kobayashi K. Plasma protein C is a useful clinical marker for hepatic veno-occlusive disease (VOD) in stem cell transplantation. Pediatr Blood Cancer 2010; 54:437.
  18. Coppell JA, Richardson PG, Soiffer R, et al. Hepatic veno-occlusive disease following stem cell transplantation: incidence, clinical course, and outcome. Biol Blood Marrow Transplant 2010; 16:157.
  19. McDonald GB, Hinds MS, Fisher LD, et al. Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients. Ann Intern Med 1993; 118:255.
  20. Carreras E, Bertz H, Arcese W, et al. Incidence and outcome of hepatic veno-occlusive disease after blood or marrow transplantation: a prospective cohort study of the European Group for Blood and Marrow Transplantation. European Group for Blood and Marrow Transplantation Chronic Leukemia Working Party. Blood 1998; 92:3599.
  21. Cesaro S, Pillon M, Talenti E, et al. A prospective survey on incidence, risk factors and therapy of hepatic veno-occlusive disease in children after hematopoietic stem cell transplantation. Haematologica 2005; 90:1396.
  22. Corbacioglu S, Hönig M, Lahr G, et al. Stem cell transplantation in children with infantile osteopetrosis is associated with a high incidence of VOD, which could be prevented with defibrotide. Bone Marrow Transplant 2006; 38:547.
  23. Ouachée-Chardin M, Elie C, de Saint Basile G, et al. Hematopoietic stem cell transplantation in hemophagocytic lymphohistiocytosis: a single-center report of 48 patients. Pediatrics 2006; 117:e743.
  24. Naithani R, Asim M, Naqvi A, et al. Increased complications and morbidity in children with hemophagocytic lymphohistiocytosis undergoing hematopoietic stem cell transplantation. Clin Transplant 2013; 27:248.
  25. Matute-Bello G, McDonald GD, Hinds MS, et al. Association of pulmonary function testing abnormalities and severe veno-occlusive disease of the liver after marrow transplantation. Bone Marrow Transplant 1998; 21:1125.
  26. Maradei SC, Maiolino A, de Azevedo AM, et al. Serum ferritin as risk factor for sinusoidal obstruction syndrome of the liver in patients undergoing hematopoietic stem cell transplantation. Blood 2009; 114:1270.
  27. Lee SH, Yoo KH, Sung KW, et al. Hepatic veno-occlusive disease in children after hematopoietic stem cell transplantation: incidence, risk factors, and outcome. Bone Marrow Transplant 2010; 45:1287.
  28. El-Sayed MH, El-Haddad A, Fahmy OA, et al. Liver disease is a major cause of mortality following allogeneic bone-marrow transplantation. Eur J Gastroenterol Hepatol 2004; 16:1347.
  29. Dix SP, Wingard JR, Mullins RE, et al. Association of busulfan area under the curve with veno-occlusive disease following BMT. Bone Marrow Transplant 1996; 17:225.
  30. Dulley FL, Kanfer EJ, Appelbaum FR, et al. Venocclusive disease of the liver after chemoradiotherapy and autologous bone marrow transplantation. Transplantation 1987; 43:870.
  31. Reed EC, Myerson D, Corey L, Meyers JD. Allogeneic marrow transplantation in patients positive for hepatitis B surface antigen. Blood 1991; 77:195.
  32. Lau GK, Lok AS, Liang RH, et al. Clearance of hepatitis B surface antigen after bone marrow transplantation: role of adoptive immunity transfer. Hepatology 1997; 25:1497.
  33. Frickhofen N, Wiesneth M, Jainta C, et al. Hepatitis C virus infection is a risk factor for liver failure from veno-occlusive disease after bone marrow transplantation. Blood 1994; 83:1998.
  34. Strasser SI, Myerson D, Spurgeon CL, et al. Hepatitis C virus infection and bone marrow transplantation: a cohort study with 10-year follow-up. Hepatology 1999; 29:1893.
  35. Rodriguez-Iñigo E, Tomás JF, Gómez-García de Soria V, et al. Hepatitis C and G virus infection and liver dysfunction after allogeneic bone marrow transplantation: results from a prospective study. Blood 1997; 90:1326.
  36. Locasciulli A, Bacigalupo A, VanLint MT, et al. Hepatitis C virus infection and liver failure in patients undergoing allogeneic bone marrow transplantation. Bone Marrow Transplant 1995; 16:407.
  37. Norol F, Roche B, Girardin MF, et al. Hepatitis C virus infection and allogeneic bone marrow transplantation. Transplantation 1994; 57:393.
  38. Locasciulli A, Testa M, Pontisso P, et al. Hepatitis C virus genotypes and liver disease in patients undergoing allogeneic bone marrow transplantation. Bone Marrow Transplant 1997; 19:237.
  39. Clift RA, Buckner CD, Appelbaum FR, et al. Allogeneic marrow transplantation in patients with acute myeloid leukemia in first remission: a randomized trial of two irradiation regimens. Blood 1990; 76:1867.
  40. Deeg HJ, Sullivan KM, Buckner CD, et al. Marrow transplantation for acute nonlymphoblastic leukemia in first remission: toxicity and long-term follow-up of patients conditioned with single dose or fractionated total body irradiation. Bone Marrow Transplant 1986; 1:151.
  41. Girinsky T, Benhamou E, Bourhis JH, et al. Prospective randomized comparison of single-dose versus hyperfractionated total-body irradiation in patients with hematologic malignancies. J Clin Oncol 2000; 18:981.
  42. Marsh JC. Hepatic vascular toxicity of dacarbazine (DTIC): not a rare complication. Hepatology 1989; 9:790.
  43. Morgan M, Dodds A, Atkinson K, et al. The toxicity of busulphan and cyclophosphamide as the preparative regimen for bone marrow transplantation. Br J Haematol 1991; 77:529.
  44. Lee JH, Choi SJ, Lee JH, et al. Decreased incidence of hepatic veno-occlusive disease and fewer hemostatic derangements associated with intravenous busulfan vs oral busulfan in adults conditioned with busulfan + cyclophosphamide for allogeneic bone marrow transplantation. Ann Hematol 2005; 84:321.
  45. Wall DA, Chan KW, Nieder ML, et al. Safety, efficacy, and pharmacokinetics of intravenous busulfan in children undergoing allogeneic hematopoietic stem cell transplantation. Pediatr Blood Cancer 2010; 54:291.
  46. Takahashi M, Harada S, Suzuki H, et al. Regorafenib could cause sinusoidal obstruction syndrome. J Gastrointest Oncol 2016; 7:E41.
  47. Choi JH, Won YW, Kim HS, et al. Oxaliplatin-induced sinusoidal obstruction syndrome mimicking metastatic colon cancer in the liver. Oncol Lett 2016; 11:2861.
  48. Magwood-Golston JS, Kessler S, Bennett CL. Evaluation of gemtuzumab ozogamycin associated sinusoidal obstructive syndrome: Findings from an academic pharmacovigilance program review and a pharmaceutical sponsored registry. Leuk Res 2016; 44:61.
  49. Vassal G, Hartmann O, Benhamou E. Busulfan and veno-occlusive disease of the liver. Ann Intern Med 1990; 112:881.
  50. McDonald GB, Slattery JT, Bouvier ME, et al. Cyclophosphamide metabolism, liver toxicity, and mortality following hematopoietic stem cell transplantation. Blood 2003; 101:2043.
  51. de Jonge ME, Huitema AD, Beijnen JH, Rodenhuis S. High exposures to bioactivated cyclophosphamide are related to the occurrence of veno-occlusive disease of the liver following high-dose chemotherapy. Br J Cancer 2006; 94:1226.
  52. Cutler C, Stevenson K, Kim HT, et al. Sirolimus is associated with veno-occlusive disease of the liver after myeloablative allogeneic stem cell transplantation. Blood 2008; 112:4425.
  53. Shulman HM, Hinterberger W. Hepatic veno-occlusive disease--liver toxicity syndrome after bone marrow transplantation. Bone Marrow Transplant 1992; 10:197.
  54. Ganem G, Saint-Marc Girardin MF, Kuentz M, et al. Venocclusive disease of the liver after allogeneic bone marrow transplantation in man. Int J Radiat Oncol Biol Phys 1988; 14:879.
  55. Nevill TJ, Barnett MJ, Klingemann HG, et al. Regimen-related toxicity of a busulfan-cyclophosphamide conditioning regimen in 70 patients undergoing allogeneic bone marrow transplantation. J Clin Oncol 1991; 9:1224.
  56. Klingemann HG, Shepherd JD, Reece DE, et al. Regimen-related acute toxicities: pathophysiology, risk factors, clinical evaluation and preventive strategies. Bone Marrow Transplant 1994; 14 Suppl 4:S14.
  57. Hägglund H, Remberger M, Klaesson S, et al. Norethisterone treatment, a major risk-factor for veno-occlusive disease in the liver after allogeneic bone marrow transplantation. Blood 1998; 92:4568.
  58. Bearman SI. The syndrome of hepatic veno-occlusive disease after marrow transplantation. Blood 1995; 85:3005.
  59. Richardson P, Guinan E. The pathology, diagnosis, and treatment of hepatic veno-occlusive disease: current status and novel approaches. Br J Haematol 1999; 107:485.
  60. Rio B, Andreu G, Nicod A, et al. Thrombocytopenia in venocclusive disease after bone marrow transplantation or chemotherapy. Blood 1986; 67:1773.
  61. Zager RA. Acute renal failure in the setting of bone marrow transplantation. Kidney Int 1994; 46:1443.
  62. Hahn T, Rondeau C, Shaukat A, et al. Acute renal failure requiring dialysis after allogeneic blood and marrow transplantation identifies very poor prognosis patients. Bone Marrow Transplant 2003; 32:405.
  63. Sharafuddin MJ, Foshager MC, Steinbuch M, et al. Sonographic findings in bone marrow transplant patients with symptomatic hepatic venoocclusive disease. J Ultrasound Med 1997; 16:575.
  64. Herbetko J, Grigg AP, Buckley AR, Phillips GL. Venoocclusive liver disease after bone marrow transplantation: findings at duplex sonography. AJR Am J Roentgenol 1992; 158:1001.
  65. Teefey SA, Brink JA, Borson RA, Middleton WD. Diagnosis of venoocclusive disease of the liver after bone marrow transplantation: value of duplex sonography. AJR Am J Roentgenol 1995; 164:1397.
  66. Hommeyer SC, Teefey SA, Jacobson AF, et al. Venocclusive disease of the liver: prospective study of US evaluation. Radiology 1992; 184:683.
  67. Vreuls CP, Driessen A, Olde Damink SW, et al. Sinusoidal obstruction syndrome (SOS): A light and electron microscopy study in human liver. Micron 2016; 84:17.
  68. Shulman HM, Gooley T, Dudley MD, et al. Utility of transvenous liver biopsies and wedged hepatic venous pressure measurements in sixty marrow transplant recipients. Transplantation 1995; 59:1015.
  69. Ho GT, Parker A, MacKenzie JF, et al. Abnormal liver function tests following bone marrow transplantation: aetiology and role of liver biopsy. Eur J Gastroenterol Hepatol 2004; 16:157.
  70. Jones RJ, Lee KS, Beschorner WE, et al. Venoocclusive disease of the liver following bone marrow transplantation. Transplantation 1987; 44:778.
  71. Carreras E, Grañena A, Navasa M, et al. On the reliability of clinical criteria for the diagnosis of hepatic veno-occlusive disease. Ann Hematol 1993; 66:77.
  72. Lee JH. Biomarkers for hepatic sinusoidal obstruction syndrome after hematopoietic cell transplantation. Blood Res 2015; 50:123.
  73. Akil A, Zhang Q, Mumaw CL, et al. Biomarkers for Diagnosis and Prognosis of Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant 2015; 21:1739.