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hepatic veno-occlusive disease

Wednesday 17 November 2004

Definition: Hepatic VOD consists of occlusive fibrosis of small intrahepatc veins: centrilobular and sublobular venules. Lager veins and those affected by Budd-Chiari syndrome are spared.

The term veno-occlusive disease of the liver refers to a form of toxic liver injury characterized clinically by the development of hepatomegaly, ascites, and jaundice, and histologically by diffuse damage in the centrilobular zone of the liver.

The cardinal histologic features of this injury are marked sinusoidal fibrosis, necrosis of pericentral hepatocytes, and narrowing and eventual fibrosis of central veins.

The primary site of the toxic injury is sinusoidal endothelial cells, followed by a series of biologic processes that lead to circulatory compromise of centrilobular hepatocytes, fibrosis, and obstruction of liver blood flow.

A more appropriate name for this form of liver injury "sinusoidal obstruction syndrome" have been proposed.


- diffuse occlusive lesions of central veins

  • central vein stenosis
  • fibrous intimal thickening, concentric intimal thickening
  • severe centrilobular necrosis, centrilobular hemorrhagic necrosis, hepatocyte dropout
  • centrilobular sinusoidal dilatation (congestion)
  • sinusoidal hemorrhage
  • obliterative fibrosis
  • pericentral fibrosis (perivenular fibrosis)

- diffuse occlusive lesions of portal veins

Evolutive forms

- Early lesions

  • subendothelial edema
  • centrolobular congestion of the pericentral sinusoids
  • blockage of blood flow in the pericentral sinusoids by fibrin and platelet aggregates
  • pericentral sinusoids plugged with fibrin, fibrin deposition
  • sinusoidal dilatation
  • centrilobular hemorrhagic necrosis

- late lesions

  • intraluminal fibrosis
  • concentric intimal thickening
  • occlusive fibrosis of small intrahepatic veins (centrolobular veins and sublobular venules), fibrous obliteration of hepatic veins
  • concentric occlusion of the affected veins by loose connective tissue
  • fibrotic scar replacing the centrilobular vein
  • centrolobular fibrosis
  • centro-portal bridging
  • cirrhosis


- bone marrow allograft conditioning (BMA-VOD)

  • stem cell transplantation (16773513)
  • onset of the disorder : 3-4 weeks after transplantation
  • frequency: 20% of cases
  • mortality rate: 50%
  • etiology: cyclophosphamide, alkalating agents, total body irradiation

- irradiation (10 Gy of irradiation with chemotherapy; 30Gy without chemotherapy)

- antineoplastic drugs

  • azathioprine (may cause the lesion many months after continuous administration)
  • 6-mercaptopurine
  • 6-thioguanine
  • mitomycin C
  • BCNU(carmustine)
  • vincristine
  • adriamycin
  • intraarterial 5-FU (2531719)
  • mitomycine C (6806170)
  • gemtuzumab

- liver allograft (1.9%) (12640317, 11602848, 8276346, 10534334)

- pyrrolizidine alkaloids

  • found in about 300 species of plants
  • examples: Heliotropium , Crotolaria and Senecio (Senescia sp.)
  • herbal teas and enemas
  • chinese palatable local dishes (17075995)

- alcoholic liver
- congenital immunodeficiency
- dimethylnitrosamine
- oral contraceptives (estrogenic steroids) (992650)
- anabolic steroids
- aflatoxin


- fetal hepatic veno-occlusive disease (12835579)

  • pyrrolizidine alkaloids of food origin

See also

- veno-occlusive lesions
- veno-occlusive diseases
- bone marrow allograft vasculopathies (BMA vasculopathies)
- veno-occlusive disease (VOD)

  • liver allograft VOD
  • pulmonary VOD (pulmonary veno-occlusive disease)

Case records

- Case #8718


- Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). DeLeve LD, Shulman HM, McDonald GB. Semin Liver Dis. 2002 Feb;22(1):27-42. PMID: 11928077