Pathology of the liver in budd-chiari syndrome: Portal vein thrombosis and the histogenesis of veno-centric cirrhosis, veno-portal cirrhosis, and large regenerative nodules

Abstract

Hepatic vein (HV) thrombosis causes ascites, hepatomegaly, and severe congestion of the liver (Budd‐Chiari syndrome [BCS]). Severe hepatic fibrosis develops in this syndrome with a variety of histological patterns. Some livers have a pattern of cirrhosis in which there is fibrous bridging between HVs and portal tracts (veno‐portal cirrhosis). Other livers have a pattern of “reversed‐lobulation cirrhosis” (veno‐centric cirrhosis), in which fibrous bridging between HVs and portal tracts is minimal. The prevalence and pathogenesis of these forms of cirrhosis and the effect of portal vein (PV) thrombosis in this disease have not been studied. We examined 15 resected livers from patients with BCS to determine the distribution of vascular obstruction and the character of the parenchymal response. Six livers had veno‐portal cirrhosis, and all of these had severe PV obliteration caused by thrombosis. Three livers had veno‐centric cirrhosis and had normal medium and large PVs. The remaining six livers had mixed veno‐centric/veno‐portal cirrhosis and had moderate PV obliteration. The nodules in veno‐centric cirrhosis had evidence of an unusual circulation with small arteries supplying a midzonal venous plexus that appeared to drain retrogradely into patent small PVs. Nine livers had large regenerative nodules histologically similar to focal nodular hyperplasia. PV thrombosis is a frequent occurrence in BCS. The correlation between PV thrombosis and the pattern of cirrhosis suggests a role for PV obliteration in the genesis of veno‐portal bridging fibrosis in this disease and possibly in other diseases leading to cirrhosis.

Histologic changes mimicking biliary disease in liver biopsies with venous outflow impairment

“…Many studies have described the histopathologic findings in hepatic venous outflow impairment. 2,3,[6][7][8][9][10][11] Most patients show evidence of chronic passive congestion, which manifests as sinusoidal dilatation and varying degree of hepatic atrophy and necrosis. The congestion and necrosis are most marked in zone 3 of the acinus, but can involve zones 1 and 2 in more severe cases.…”

“…These changes are well described in several articles and details of the changes in sinusoidal blood flow and mechanism of central-central and central-portal fibrosis have been studied. 2,3,[6][7][8][9][10][11] However, histologic features in portal tracts in liver biopsies with venous outflow impairment have not been detailed in any of these publications [1][2][3][4][5][6][7][8][9][10][11] or standard liver textbooks. 12,13 In our experience, abnormal portal tracts are often seen in venous outflow impairment and can mimic the findings of chronic biliary disease.…”

Liver cirrhosis and hepatocellular carcinoma in hepatic vena cava disease, a liver disease caused by obstruction of inferior vena cava

“…Thrombotic obstruction of portal vein radical in this situation was thus likely to cause more damage to hepatocytes. Further occurrence of thrombotic obstruction of the small hepatic and portal veins of the same area was likely to be associated with massive necrosis of the hepatocytes [30].…”

“…Unlike in chronic viral infection, there was absence of necroinflammation in HVD, indicating absence of continued liver cell damage. Prolonged congestion that resulted in loss of hepatocytes with failure to regenerate due to continuing high sinusoidal pressure and its replacement by fibrous tissue was assumed to be the mechanism of development of cirrhosis [17,[30][31][32]. Regenerative nodules formed in such patients with longstanding disease led to the development of venocentric or reversed lobulation cirrhosis [17,30].…”

“…Thus, acute disease or acute exacerbation was not only associated with HVOO but also caused thrombotic obstruction of small portal and hepatic veins. Ischemic loss of hepatocytes due to portal and hepatic vein obstruction may lead to venoportal cirrhosis [30]. Development of cirrhosis even in chronic heart failure was thought to be due to intrahepatic venous thrombosis rather than to generalized venous congestion [39].…”