Case 8 -

Hepatic Veno-occlusive Disease Alan G. Rose

Clinical History The patient was a 9-year-old girl who lived on a farm. She presented to a clinic with a history of several weeks upper abdominal pain, nausea, vomiting and abdominal swelling. Mild jaundice was evident. Autopsy revealed a marked "nutmeg" appearance of passive congestion of the liver (Figure 1) plus ascites. The histology (Figures 2-3) shows veno-occlusive disease affecting the centrilobular and sublobular veins of the liver with intense centrilobular and mid-zonal congestion with loss of hepatocytes. A reticulin stain is most useful in demonstrating the venous occlusion and / or narrowing. Case 8 - Figure 1 - Extreme nutmeg pattern of liver Case 8 - Figure 2 - Centrilobular zonal congestion and cell necrosis, (H&E) Case 8 - Figure 3 - Elastic van Gieson stain shows severe luminal narrowing of central vein due to veno-occlusive disease The Budd-Chiari syndrome was originally applied to acute, usually fatal thrombotic occlusion of the major hepatic veins close to their exit from the liver and in the intra-hepatic portion of the inferior vena cava. The definition has now been expanded to include subacute and chronic occlusive syndromes, characterized by hepatomegaly, weight gain, ascites, and abdominal pain. [1] Some causes of the syndrome are listed in Table 1. In parts of Africa and the Orient, membranous webs (? congenital in origin), narrow the inferior vena cava above the hepatic vein orifices and may cause a Budd-Chiari syndrome. Table 1: Causes of the Budd-chiari Syndrome Major Hepatic Venous Thrombosis Intra-hepatic Veno-occlusive Disease Polycythemia Vera Pregnancy Postpartum State Oral Contraceptives Paroxysmal Nocturnal Hemoglobinuria Intra-abdominal Cancers Trauma Webs in the Inferior Vena Cava Idiopathic (20%) In the acute phase of major hepatic vein thrombosis, the liver is swollen and intensely congested with a mottled cut surfaces which freely oozes blood. The dilated sinusoids compress the centrilobular liver plates with necrosis of affected hepatocytes. In the chronic phase, the liver is firmer and paler and the thrombi show evidence of organization. Fibrosis extends from the centrilobular zone to the periphery of the lobule. Erythrocytes may leak into the space of Disse. Veno-occlusive disease of the liver, [2 ]which comprises an endophlebitis and thrombosis affecting central and sublobular veins, may present with the Chiari syndrome. The known causes of hepatic veno-occlusive disease (Table 2) include the following: chemotherapy e.g. Mitomycin C [3] and bone marrow transplantation pre-treatment with busulphan and cyclophosphamide. [4] Graft-versus-host disease may also play a role in its pathogenesis in some cases. In the West Indies, South America and South Africa hepatic veno-occlusive (HVOD) has resulted from ingestion of pyrrolizine alkaloids due to the ingestion of "bush tea" or contamination of wheat by plants (e.g. Senecio, Crotalaria and Heliotropium) producing hepatotoxic alkaloids. [5] The case illustrated had HVOD due to ingestion of senecio alkaloids that contaminated wheat. The primary injurious action in humans is on the central and sublobular hepatic veins. Idiopathic hepatic lipogranulomatosis may simulate veno-occlusive disease of the liver. [6] Milder, non-specific veno-occlusive lesions have also been noted in the livers of alcoholics, [7] which may also show perivenular fibrosis or chronic lymphocytic phlebitis. In veno-occlusive disease thrombotic occlusion occurs in the intra-hepatic terminal hepatic venules sometimes extending into the sublobular veins. Table 2: Causes of Intra-hepatic Veno-occlusive Disease Toxic Pyrrolizidine Alkaloids (Plants: Crotalaria and Senecio Families) Anti-cancer Chemotherapy Hepatic Irradiation Bone Marrow Transplantation References Crawford JM. The liver and the biliary tract. In: Cotran RS, Kumar V, Collins T (eds), Robbins pathologic basis of disease, 6th edition. Philadelphia, W B Saunders Company, 1999, pp845-901. Ludwig J, et al. Classification of hepatic venous outflow obstruction: Ambiguous terminology of the Budd-Chiari syndrome. Mayo Clinic Proc 1990; 65: 51-55. Lazarus HM, Gottfried MR, Herzig RH, et al. Veno-occlusive disease of the liver after high-dose mitomycin C therapy and autologous bone marrow transplantation. Cancer 1982; 49: 1789- 1795. Krivit W, Freese D, Chan KW, Kulkarni R. Wolman's disease: review of treatment with bone marrow transplantation and considerations for the future. Bone Marrow Transplant 1992; 10 (suppl. 1): 97-101. Rose AG. Diseases of veins. In: Silver MD (ed), Cardiovascular Pathology, 2nd edition, Churchill Livingstone, New York, 1991, pp 195-223. Keen MF, Engstrand DA, Hafez GR. Hepatic lipogranulomatosis simulating veno-occlusive disease of the liver. Arch Pathol Lab Med 1985; 109: 70- 72. Goodman ZD, Ishak KG. Occlusive venous lesions in alcoholic liver diseases. A study of 200 cases. Gastroenterology 1982; 83: 786- 796.