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 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
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.
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
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
). 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.
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
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.