Pathology and differential diagnosis of hepatic venous outflow impairment

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Abbreviations

SOS

sinusoidal obstructive syndrome

Findings suggestive of venous outflow impairment in liver biopsies include sinusoidal dilatation, congestion, edema, and hepatic cord compression or atrophy. Sinusoidal dilatation is a fairly common finding. From a morphological perspective, if sinusoidal dilatation is present focally in a biopsy, it is unlikely to be a significant finding. For example, the finding of sinusoidal dilatation in transplant liver biopsies is fairly common and may be dismissed easily. The finding of sinusoidal dilatation is less common in the nonsurgical setting but can be seen focally or diffusely within a biopsy. Obstruction of blood flow at the level of the vena cava or the heart will lead to diffuse changes in the liver. Localized vascular lesion or mass lesions within the liver may not. When the finding is diffuse within the biopsy, it is much more likely to represent significant disease. Blood flow studies are necessary to determine the presence of or to rule out an obstructive lesion.

The differential diagnosis is relatively small when diffuse venous outflow changes are seen in a biopsy.1, 2 Consideration includes lesions that affect the central vein, hepatic vein, vena cava, and heart. The differential includes sinusoidal obstruction syndrome (veno‐occlusive disease), Budd‐Chiari syndrome, cardiac failure, posttransplant changes, and intrahepatic mass lesions.

Sinusoidal Obstructive Syndrome

Sinusoidal obstructive syndrome (SOS) was previously known as veno‐occlusive disease. This condition is most commonly seen in patients who have undergone bone marrow or stem cell transplants. The condition has also been documented with other disorders including many autoimmune conditions. SOS is thought to be due to conditioning regimens that lead to damage of the endothelial cells at the point where the sinusoids join the central vein. This leads to damage of the endothelial cells with edema, culminating in occlusion of the sinusoids and the central vein (Fig. 1). Morphologically, the central vein shows occlusion of the lumen with collapse of the lumen with an edematous appearance. This finding is unique and is specific for SOS. There is also marked sinusoidal dilatation, congestion, and edema of the hepatic lobules. Hepatic cell atrophy or necrosis may also occur. With time, fibrosis of the central vein may be seen. The findings in the central vein may only be seen focally in a biopsy, but the other changes usually are diffuse.

Figure 1.

Liver biopsy demonstrating findings of sinusoidal obstruction syndrome. (A) There is marked edema and congestion of the hepatic sinusoids with compression of the hepatic cords. (B) A higher magnification of the central vein that shows collapse of the endothelial cells with filling of the lumen.

Budd‐Chiari Syndrome

Budd‐Chiari syndrome occurs when the large hepatic veins are partially or completely occluded by a thrombus. Patients may present with acute liver failure, but usually present with acute liver disease. Chronic presentations have also been documented. In the vast majority of patients, an underlying hypercoagulable state or risk factor can be demonstrated. The typical histopathological findings include marked sinusoidal dilatation with congestion, edema, and occasionally pericentral necrosis (Fig. 2). Although central vein thrombus may be seen, collapse of the endothelial cells is not seen, in direct contrast with SOS. Central inflammation has been described in approximately 30% of patients. Centrilobular bile ductules and arterioles have also been described.

Figure 2.

Budd‐Chiari syndrome. (A) Low‐power magnification of a liver biopsy is seen with prominent sinusoidal dilatation in the pericentral region. (B) Higher magnification with marked sinusoidal dilatation and congestion in the pericentral region. Hepatocyte loss may also occur. Central vein thrombi may be seen, but endothelial collapse is not present.

Cardiac (Congestive) Hepatopathy

Cardiac hepatopathy refers to liver dysfunction that is caused by passive congestion of the liver due to right‐heart failure. Because of right‐heart failure, the blood is not cleared from the liver, resulting in chronic passive congestion. Although this is generally a chronic condition, acute presentations can occur. Although the patient's heart condition is usually known to treating physicians, liver biopsy may be performed to rule out other hepatic pathology. Most commonly this occurs during work‐up of the patient for cardiac or renal transplantation. The gross morphological appearance of the liver has a resemblance to nutmegs and has classically been referred to as the nutmeg liver (Fig. 3A). The liver histology in the early stages shows sinusoidal dilatation with edema and congestion (Fig. 3B). With chronic passive congestion, pericentral fibrosis occurs, which could lead to bridging (central to central) fibrosis and ultimately cirrhosis.

Figure 3.

Cardiac (congestive) hepatopathy. (A) Gross photograph of a liver with classic nutmeg appearance. (B) Early passive congestion with sinusoidal dilatation. (C) Microscopic images of congestive hepatopathy demonstrating marked pericentral congestion with central‐central bridging fibrosis. The higher magnification demonstrates a normal portal tract in the middle of the image with congestion and fibrosis of the central‐lobular region.

Posttransplant Changes

Sinusoidal dilatation is not uncommonly seen in post‐liver transplant biopsies. The majority of patients with this finding may have some abnormality of their liver enzyme tests, but usually do not have identifiable physical venous outflow obstruction. It is thought that remodeling of the liver posttransplant because of subtle injury may lead to vascular alterations that are manifested as sinusoidal dilatation and congestion. Similar findings can also be seen in the setting of intrahepatic mass lesions, granulomatous disease, and systemic inflammatory conditions.

Morphological Considerations

With prolonged venous congestion and sinusoidal dilatation, pericentral necrosis and fibrosis may develop (Fig. 4). Additional findings that could be seen with time are aberrant ductular proliferation as well as aberrant arterioles found in the pericentral location.

Figure 4.

(A) A case of prolonged venous outflow impairment demonstrating pericentral necrosis, hemorrhage, and fibrosis. The central vein (star) is seen with adjacent loss of hepatocytes combined with hemorrhage and fibrosis. (B) Higher magnification of the same case demonstrating fibrosis with ductular proliferation (arrow).