Vascular Disorders

Vascular Disorders

Lizhi Zhang, MD


The liver has a dual blood supply. The portal vein provides approximately two-thirds of blood flow to the liver, with blood that is rich in nutrients. The hepatic artery supplies the rest of the blood, with blood that is oxygen rich. The hepatic veins drain the venous blood into the inferior vena cava and then back to the right side of the heart. A variety of abnormalities can occur at any level of blood inflow to the liver or blood outflow of the liver. These abnormalities can be either extrahepatic or intrahepatic and can lead to ischemia, portal hypertension, liver fibrosis and cirrhosis, or liver architectural alterations.


Normal variants

Variations in the anatomy of the portal vein and the hepatic artery are common. For example, variants in the branching pattern of intrahepatic portal veins are observed in approximately 20% of the population. The most common of these variant patterns include trifurcation of the main portal vein, or a right posterior segmental branch arising from the main portal vein, or a right anterior segmental branch arising from the left portal vein.1 Variations in the classic branching of the hepatic artery are seen in 40% to 45% of people, with the most common patterns being a right hepatic artery arising from the superior mesentery artery or a left hepatic artery arising from the left gastric artery. Interestingly, an abnormal origin of the hepatic artery is frequently associated with biliary atresia.2 Knowing these variants is particularly important for liver transplant surgeons because ligation of these branches may lead to liver necrosis, bile duct injury, or allograft failure.

Arteriovenous malformation

Arteriovenous malformations are congenitally abnormal direct connections between arteries and veins, which are usually localized to one lobe of the liver. Neonates with hepatic arteriovenous malformations can present clinically with congestive heart failure, anemia, hepatomegaly, and portal hypertension. Syndromic forms of vascular
malformations, such as hereditary hemorrhagic telangiectasia, can also have arteriovenous malformations that manifest in late childhood with congestive heart failure and portal hypertension. Hepatic arteriovenous malformations are typically diagnosed by imaging or angiography and are rarely biopsied. In some cases, they may be resected.

Microscopically, arteriovenous malformations are characterized by large vessels with thick fibromuscular walls (Fig. 21.1). The center of the lesion can show infarction, hemorrhage, and calcification, whereas the peripheral of the lesion typically shows a marked fibrovascular proliferation (Fig. 21.2). Of note, infantile hemangioma has some overlapping clinical and radiologic features with arteriovenous malformations.3,4 However, they are biologically and histologically distinct lesions. GLUT-1 immunostain can also help distinguish these two entities because the endothelial cells are positive for GLUT-1 in infantile hemangiomas but are negative in arteriovenous malformations.5

Figure 21.1 Hepatic arteriovenous malformation. The lesion is composed of large vessels with thick fibromuscular walls.

Figure 21.2 Hepatic arteriovenous malformation. There is a fibrovascular proliferation with calcification at the periphery.

Arterioportal fistula

Although most arterioportal fistulas are acquired because of cirrhosis, other rare causes include hepatic neoplasms, trauma, and rare cases of congenital arterioportal fistulas. Most patients with congenital arterioportal fistulas become symptomatic within the first year of life owing to portal hypertension, but the age of presentations varies. Arterioportal fistulas can also be associated with biliary atresia or hereditary hemorrhagic telangiectasia, although no other disease is seen in most cases.6 Doppler ultrasound is the most useful method for making the diagnosis, which typically shows enlargement of the hepatic artery and dilatation of the segment of the portal vein, where the fistula is located. If left untreated, the liver may develop portal fibrosis and hepatoportal sclerosis.

Extrahepatic portosystemic shunt (Abernethy malformation)

Extrahepatic portosystemic shunt, also known as Abernethy malformation, is a rare congenital malformation in which portal blood is diverted away from the liver and drains into systemic veins. It has been classified into two subgroups. In type 1, there is congenital absence of the portal vein, and the portal blood is completely diverted into the inferior vena cava. This subgroup is further subdivided into type 1a, in which the splenic and superior mesenteric veins drain separately into the systemic veins, and type 1b, in which the splenic and superior mesenteric veins join to form a common trunk before draining into the inferior vena cava. In the type 2 Abernethy malformation, the portal vein is present and there is partial portal blood flow to the liver, but some of the portal flow is diverted into the inferior vena cava through a side-to-side extrahepatic communication.7

The clinical presentation of Abernethy malformation varies significantly. Some cases may be entirely asymptomatic or only have mild elevations of liver enzymes and bilirubin levels, whereas other cases may have serious complications, such as pulmonary hypertension, hepatopulmonary syndrome, hyperammonemia, or hepatic encephalopathy.8 Abernethy malformation is occasionally diagnosed in adulthood. Abernethy malformations are also associated with the development of focal nodular hyperplasia, hepatic adenomas, and hepatocellular carcinoma.9,10 Cross-sectional imaging can readily identify the portosystemic shunt and the absent vessels.

Microscopically, the liver parenchyma changes in Abernethy malformation are characterized by the absence or paucity of portal vein branches in the small portal tracts, and hypoplastic veins or fibrotic remnants in medium-sized portal tracts. The hepatic arteries are large and thickened, crowding the portal tracts with a disordered tangle of vessels (Figs. 21.3 and 21.4). Bile duct changes are generally absent to mild, but there can be a mild bile ductular proliferation and focal periductal fibrosis. Prominent, dilated lymphatic channels at the periphery of portal tracts are described in some cases. The lobules often show mild sinusoidal dilation, small lobular arterioles, and nodular regenerative hyperplasia. Nodular regenerating hyperplasia, when present, can be highlighted by a reticulin stain. Trichrome stains usually show mild portal fibrosis, fibrotic remnants of portal veins, and hypoplastic portal vein branches with narrow lumens and thickened muscle bundles.10
Abernethy malformations can occasionally be encountered in liver resections for hepatocellular carcinoma arising in noncirrhotic livers.10

Figure 21.3 Abernethy malformation. The biopsy shows portal tracts without portal vein branches.

Figure 21.4 Abernethy malformation. An isolated capillary is seen in the lobule (arrow).

Intrahepatic portosystemic shunt

Congenital intrahepatic portosystemic shunts are abnormal intrahepatic connections between branches of the portal veins and the hepatic veins. This condition can be complicated by congestive heart failure, portal hypertension, portosystemic encephalopathy, and cirrhosis. In the most common form, there is a connection between the right portal vein and the inferior vena cava through a single large shunting vessel. Congenital intrahepatic portosystemic shunts can also present with a localized communication or multiple communications between peripheral portal veins and hepatic veins.11 A persistent ductus venosus is also considered to be a type of portosystemic shunt. The diagnosis is usually made with Doppler ultrasound, which demonstrates the vascular nature of the shunt and the amount of blood being shunted. As a result of the abnormal blood flow, the liver can develop nodular regenerative hyperplasia and/or focal nodular hyperplasia.12 There are also acquired forms of intrahepatic portosystemic shunts that are associated with cirrhosis, hepatocellular carcinoma, or traumatic injuries to the liver.

Hepatic vascular disorders associated with other congenital syndromes

Turner syndrome

Turner syndrome is one of the most common chromosomal abnormalities and results from a missing X chromosome in females. There is a wide range of signs and symptoms, and some affected individuals may have less obvious or less severe physical findings. The classic phenotype of Turner syndrome is short stature, broad chest, webbed neck, low set ears, and gonadal dysgenesis. Abnormal liver tests are frequent in patients with the Turner syndrome, and most of them present with steatosis and steatohepatitis due to being overweight. Biliary disease has also been reported, including a wide range of findings such as biliary atresia, sclerosing cholangitis, and paucity of bile ducts.15 Liver architectural changes can also develop, such as nodular regenerative hyperplasia or focal nodular hyperplasia, which are associated with vascular changes, including obliterative portal venopathy, or with congenital vascular disorders such as hypoplasia or agenesis of the portal venous system.15,16 Cirrhosis may develop in some affected individuals, but it is often unclear if the cirrhosis is due to the fatty liver disease or the vascular abnormalities, or both.15

Hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia, also known as Osler-Weber-Rendu syndrome, is an autosomal dominant genetic disorder leading to abnormal blood vessel formation in the skin, mucous membranes, and various organs including the liver. There are five genetic types of hereditary hemorrhagic telangiectasia. Mutations have been identified in three specific genes (ENG, ALK1, and SMAD4), whereas the other two types of hereditary hemorrhagic telangiectasia have to date been linked only to loss of DNA on a particular locus. The subtype associated with ALK1 mutations is most likely to have liver disease.

Hereditary hemorrhagic telangiectasia is manifested by telangiectasia (small vessel malformations) and arteriovenous malformations (large vessel malformations). Liver involvement is common in hereditary hemorrhagic telangiectasia, but the majority of individuals are asymptomatic. Overall, 10% of individuals can present with clinical findings that result from portal hypertension, biliary disease, or high-output heart failure.17 Hepatic arteriovenous malformations can be seen in 50% to 75% of individuals, whereas telangiectasias are less commonly seen.18 Livers are generally not biopsied in cases of known hereditary hemorrhagic telangiectasia because of the risk of bleeding. However, some cases undergo liver biopsy because imaging studies show lesions in individuals without a known diagnosis of hereditary hemorrhagic telangiectasia. Histologically, arteriovenous malformations are characterized by large caliber vessels with abnormal thick fibromuscular walls and direct shunts between portal arterioles and veins. These shunts can lead to focal nodular hyperplasias, which are the most common mass lesions found in patients with hereditary hemorrhagic telangiectasia. Histologically, the focal nodular hyperplasias are similar to those in the sporadic setting.19

Other vascular lesions are telangiectasias. These lesions can be focal microscopic collections of dilated inter-anastomosing vessels in the portal tracts, with sinusoidal dilation at the periphery (Fig. 21.5). In other cases, the telangiectasias can be large and mass forming. Mass-forming lesions are characterized by interanastomosing vascular channels that in some areas can show direct connections to the portal veins (Fig. 21.6). The lesion is composed of thin-walled vascular channels that are lined by bland endothelium with a very low or absent proliferative rate. The channels can dissect into the hepatic parenchyma, leaving intact portal tracts and hepatic lobules. The hepatic lobules can also show sinusoidal dilation and mild hyperplasia but do not show well-defined regenerative nodules. Focal hemorrhage with fibrosis and hemosiderin-laden macrophages are often seen within larger telangiectasias. Hepatocellular carcinomas have also been reported.20

Figure 21.5 Liver involvement in hereditary hemorrhagic telangiectasia (HHT). Arteriovenous malformation in HHT characterized by dilated vessels with thick fibromuscular walls and direct shunts between portal arterioles and veins.

Figure 21.6 Mass-forming telangiectasia in hereditary hemorrhagic telangiectasia. The lesion is characterized by interanastomosing vessels connected directly with the portal veins.

Hereditary hemorrhagic telangiectasia is usually managed conservatively, but liver transplantation is used in cases with cardiac failure, liver failure, massive biliary necrosis, or severe portal hypertension. Vascular abnormalities and lesions, such as arteriovenous malformations, intrahepatic shunts, hemangioma, hemorrhagic foci, ischemic liver and biliary necrosis, and peliosis, are universally identified in the explants (Fig. 21.7). The explanted livers show a range of findings, but commonly include nodular regenerative hyperplasia (in noncirrhotic livers), focal nodular hyperplasia, arteriovenous malformations, and telangiectasias. Advanced fibrosis or cirrhosis is seen up to one-third of patients.21

Figure 21.7 A liver explant of hereditary hemorrhagic telangiectasia shows patchy red telangiectasias.


Portal vein thrombosis

Clinical features

Portal vein thrombosis is a relatively rare disorder with an overall incidence of 0.05% to 0.5%, but the reported incidence in people with cirrhosis varies from 0.6% to 16%.22 In the acute phase, patients may be asymptomatic or have nonspecific features such as fever or abdominal pain. In chronic cases, symptoms and signs related to portal hypertension can develop. In fact, approximately 5% to 10% of all cases of portal hypertension are due to portal vein thrombosis.

The clinical presentations also vary with different underlying causes of liver disease, which can be either inherited or acquired. In children and neonates, intra-abdominal infection is the leading cause of portal vein thrombosis, with the remaining cases due to congenital anomalies of the portal venous system, or due to neonatal sepsis with umbilical catheter placement. In adults, cirrhosis and neoplasms are the main causes. Individuals with coagulopathy are at particularly high risk of thrombosis. Of note, 8% to 15% of portal vein thrombosis cases are idiopathic.23

Laboratory findings

In patients with portal vein thrombosis, the liver enzymes are generally normal or only mildly elevated, unless there is coexistence of an underlying liver disease or cirrhosis. Coagulation tests are often abnormal because of the inherited coagulation disorders and/or underlying hepatic insufficiency.


Ultrasound can quickly establish the diagnosis of portal vein thrombosis by revealing the presence of solid, hyperechoic material in a distended portal vein or its tributaries and the presence of collateral vessels. Doppler imaging can confirm the absence of flow in part or all of the vessel lumen. Endoscopic ultrasound is even more sensitive and specific and can detect small and nonoccluding thrombi. Computed tomography (CT) scan demonstrates hyperattenuating material in the portal vein lumen and the absence of enhancement after contrast injection.

Gross findings

The liver can be diffusely atrophic if the main portal vein trunk is blocked. Liver parenchyma remodeling occurs after partial recanalization of the vein, or with compensatory hyperflow from the hepatic artery. This parenchymal remodeling can lead to generalized nodular regenerative hyperplasia or focal nodular hyperplasia.

Acute thrombosis of small hepatic veins can lead to pseudoinfarctions, also known as Zahn infarcts, characterized by a focal area of congestion associated with hepatocellular atrophy but no necrosis.

Liver explants with portal vein thrombosis usually show underlying cirrhosis because of concurrent chronic liver diseases, such as chronic viral hepatitis or fatty liver disease. Organized thrombi or webs can be identified in the portal vein branches (Fig. 21.8).

Figure 21.8 Portal vein thrombosis. A large thrombus was identified in liver explant.

Microscopic findings

Changes in the portal veins include organizing and recanalized thrombi, eccentric intimal fibrosis of the vein wall, luminal webs, and in long-standing cases, partial or complete absence of the veins, being replaced by fibrotic scars (Fig. 21.9). The morphologic changes within the hepatic lobules are mild and often subtle. Typical features of nodular regenerative hyperplasia may be present. In many cases, the main finding is hepatoportal sclerosis, characterized by atrophy or complete absence of the smaller branches of the portal veins. Other portal tracts can show an increased number of small caliber portal veins or dilated portal vein branches “herniating” into the surrounding parenchyma with an “ectopic” appearance (Fig. 21.10). However, the changes of hepatoportal sclerosis are subtle and can be easily overlooked because the biopsies can appear “almost normal” on first examination. One important clue can be a clinical diagnosis of portal hypertension, but no significant fibrosis present in the biopsy.

Portal biliopathy, also known as pseudosclerosing cholangitis, is a term that describes biliary abnormalities secondary to portal hypertension.24 Most cases of portal biliopathy result from extrahepatic portal vein thrombosis,25 resulting in external compression of the bile ducts by large collaterals, leading to ischemia and strictures with subsequent episodes of infection. The portal tracts may show changes compatible with large bile duct obstruction.

Molecular genetic findings

Molecular genetic testing is not used to diagnose portal vein thrombosis but is important after a diagnosis is made in order to rule out inherited coagulation disorders such as Factor V Leiden mutation, protein C deficiency, or prothrombin mutations.

Figure 21.9 Portal vein thrombosis. Microscopic findings of an organizing portal vein thrombus with recanalization.

Figure 21.10 Portal vein thrombosis. Parenchyma changes are characterized by nodular appearance with atrophy and absent of the portal veins in the small portal tracts. Also seen are dilated portal vein branches that “herniate” into the surrounding parenchyma.

Hepatoportal sclerosis

Clinical features

Hepatoportal sclerosis is the main histologic finding of idiopathic noncirrhotic portal hypertension.29 It can occur in both pediatric populations and in adults. The etiology of hepatoportal sclerosis is idiopathic in many cases, but it can be associated with a variety of conditions including chronic or recurrent infections, hematologic disorders, exposures to drugs or toxins, immunologic disorders, genetic disorders, and hypercoagulability. Clinical manifestations are characterized by portal hypertension, but liver failure with ascites and/or encephalopathy is rare. Portal vein thrombosis is common during the course of the disease.

Laboratory findings

Liver enzymes are usually normal or just mildly elevated. Anemia, leukopenia, and thrombocytopenia are common because of hypersplenism.


Imaging studies can reveal diffuse nodularity of the liver, mimicking cirrhosis. Portal vein thrombosis and ascites can be present in some patients.

Gross findings

The liver explants can appear normal, show mild atrophy, or demonstrate a nodular parenchymal pattern. In many cases, organizing thrombi can be identified in large portal vein branches.

Microscopic findings

The diagnosis of hepatoportal sclerosis relies on identifying characteristic histopathologic features in liver biopsy specimens. A history of portal hypertension but no fibrosis on liver biopsy is an important clue to look carefully for this diagnosis. The primary findings are obliterative portal venopathy associated with liver parenchyma remodeling.29,30 The classical changes of obliterative portal venopathy include luminal narrowing and obliteration of the small portal vein branches. Other findings include the complete absence, atrophy, or fibrous scarring of portal veins (Figs. 21.11, 21.12, and 21.13). The atrophic portal veins
are much smaller in caliber, often being similar in size to that of the hepatic arterioles or bile ducts. There can be increased numbers of small caliber portal veins as well. Some portal tracts may contain prominent dilated portal vein branches “herniating” into the surrounding liver parenchyma (Fig. 21.14). The lobular parenchyma can be unremarkable or nodular regenerative hyperplasia.30 Partial nodular transformation in perihilar areas has also been observed, but this diagnosis needs to be correlated with gross or imaging findings.31

Figure 21.11 Hepatoportal sclerosis. Obliterative portal venopathy.

Figure 21.12 Hepatoportal sclerosis. An atrophic portal vein with dense fibrosis in a large portal tract.

Figure 21.13 Hepatoportal sclerosis. Remnants of a portal vein are seen as a fibrotic scar in a portal tract (Trichrome stain).

Figure 21.14 Hepatoportal sclerosis. Dilated portal veins “herniating” into the surrounding liver parenchyma.

Fibrosis is usually absent or mild. Trichrome stains can demonstrate mild portal fibrosis, but advanced fibrosis is absent. The lobules can also show perisinusoidal fibrosis,32,33 but this finding is not specific and overall tends to occur more frequently with other etiologies such as chronic venous outflow impairment or sinusoidal obstruction syndrome.

Immunohistochemistry and special stains

Trichrome stains can show portal sclerosis and fibrotic remnants of portal veins in portal tracts. Some cases may have incomplete septal fibrosis, characterized by delicate “incomplete” septal fibrosis giving a nodular appearance of liver parenchyma. Reticulin stains can highlight the changes of nodular regenerative hyperplasia.


Hepatic artery thrombosis

Hepatic artery thrombosis is a major cause of graft loss and mortality after liver transplantation (Fig. 21.15).36 It occurs more frequently in the pediatric population because of the smaller caliber of the vessels and greater fluctuations in the concentration of coagulation factors. Early onset hepatic artery thrombosis can be clinically severe and histologically can show ischemic hepatitis and biliary ischemic injury. Of note, about a third of cases of hepatic artery thrombosis can be asymptomatic.

Depending on the size and degree of thrombosis, the histologic findings can be subtle with increased lobular spotty necrosis, increased hepatocyte mitoses, and variable degrees of cholestasis (Fig. 21.16). In more severe cases, there can be bland zone 3 hepatocyte necrosis or panacinar cell necrosis. In some cases, the ischemic injury can lead to bile duct necrosis, strictures, and cholangiectases in the perihilar extrahepatic bile ducts and the large intrahepatic bile ducts.37 In these cases, peripheral liver biopsies show changes that resemble biliary obstruction, with portal edema, cholangitis, and bile ductular reaction.

In nontransplant cases, hepatic artery thrombosis can develop due to a variety of causes such as hypercoagulability disorders, severe arteriosclerosis,
vasculitis, hepatic artery aneurysm, or iatrogenic (ligation during surgery or therapeutic embolization). Individuals may be asymptomatic because of the dual blood supply of the liver, but a subset of patients may develop ischemic hepatitis with jaundice and elevated liver aminotransferase levels. Liver infarcts are more likely to occur when artery thrombosis is also associated with compromised portal vein blood flow.38 Liver infarcts are characterized by panacinar parenchymal necrosis with little or no inflammation. In some cases, the panacinar necrosis will contain residual portal tracts surrounded by a thin rim of viable liver cells. Of note, liver infarction can form a mass lesion that mimics a neoplasm.39

Figure 21.15 Hepatic artery thrombosis. A thrombus identified in portal artery in the liver explant.

Figure 21.16 Hepatic artery thrombosis. Bland ischemic necrosis predominantly involving zones 3 and 2 regions.

Hepatic artery aneurysm

Hepatic artery aneurysm is uncommon but can be caused by arteriosclerosis, infections, trauma, and vasculitis. Most aneurysms are located in the extrahepatic artery. Ruptured aneurysms may lead to death, with bleeding into the common bile duct (hemobilia), abdominal cavity, or adjacent hollow viscera.40 The diagnosis is established by imaging studies.

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Nov 24, 2019 | Posted by in GASTROENTEROLOGY | Comments Off on Vascular Disorders

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