Arteriovenous Communications

Clinical Features, Investigations, and Management

Hepatic hemangiomas are technically not arteriovenous malformations (AVMs), but rather neoplasms representing benign endothelial tumors. Hepatic hemangiomas can be broadly classified into two varieties: congenital and infantile. Both types of hemangiomas can exist in extrahepatic locations, but the cardiovascular ramifications exist only in cases of hepatic hemangioma; hence our discussion will be limited to hemangiomas presenting in the liver. Patients with hepatic hemangiomas commonly have associated skin hemangiomas, frequently multiple, and their presence may be the initial presenting feature and should prompt a search for liver hemangioma. Older literature often used the term hemangioendothelioma , but this term was imprecise and could represent different entities, including congenital or infantile hemangiomas and even malignant angiosarcomas; hence the term hemangioendothelioma is currently discouraged.

Congenital hemangioma is a benign neoplasm of endothelial origin that begins proliferating in utero and is fully formed at, or just before, birth and then follows one of three patterns of natural evolution depending on the subtype: rapidly involuting (until 15 to 24 months of age), partially involuting, or noninvoluting. Affected infants may present with liver manifestations (variceal bleeding, hepatomegaly, splenomegaly), hematologic manifestations (anemia and thrombocytopenia), and high-output CHF due to massive arteriovenous shunting. In addition, cyanosis may occur due to right-to-left shunting across intracardiac communications such as an atrial septal defect or patent arterial duct. Because congenital hemangiomas have reached their peak size at birth, these various manifestations (e.g., CHF) are usually present immediately after birth if the tumors are large enough to cause these sequelae.

The diagnosis of congenital hepatic hemangioma is usually made using noninvasive imaging. The study of choice is two-dimensional ultrasound with Doppler. The ultrasound appearance can be variable, ranging from a hypoechoic to hyperechoic mass, and larger hemangiomas can have a more complex appearance that can include calcifications, thrombosis, and fibrosis. If the diagnosis is unclear, a liver magnetic resonance imaging (MRI) study with contrast and dynamic acquisition pattern can be performed and typically reveals a hypointense lesion on T1-weighted and hyperintense lesion on T2-weighted images. Congenital hemangiomas are most commonly single tumors. The differential diagnosis of a solitary liver mass present at birth or shortly thereafter includes hepatoblastoma, metastatic neuroblastoma, or hamartoma. However, typically, hepatoblastoma would lack the rim enhancement seen in hemangiomas and would be associated with elevated α-fetoprotein levels. Although congenital hemangioma can usually be diagnosed based solely on noninvasive imaging, a biopsy may be occasionally required; it is therefore important to note that congenital hemangioma does not express glucose transporter-1 or lymphatic markers.

Congenital hemangioma can follow one of three natural patterns of evolution: rapidly involuting congenital hemangioma will typically involute within the first 24 months of life, but most regress by 3 months of age, whereas noninvoluting congenital hemangioma will generally not persist, and a third intermediate form is considered to be partially involuting.

Infantile hemangiomas are the most common of all childhood tumors and represent an entity that is distinct from congenital hemangiomas. Infantile hemangiomas continue to proliferate after birth and may reach peak size by 6 to 12 months of age, whether these are cutaneous, hepatic, or in other locations. Although infantile hemangiomas can present with very similar hematologic, hepatic, and cardiovascular manifestations as congenital hemangiomas, an important distinction is that in infantile hemangiomas these features will not be present at birth but may develop during infancy if the tumor mass reaches a sufficient size. Another distinguishing feature is that infantile hemangiomas may express high levels of type 3 iodothyronine deiodinase, leading to inactivation of circulating thyroid hormone and clinical hypothyroidism. It is important to note that this form of infantile hypothyroidism would not be detected by newborn screening because it is expected to develop only after several months of tumor growth.

The diagnosis of infantile liver hemangiomas is usually also made based on noninvasive imaging, usually ultrasound with Doppler, although liver MRI also plays an important role. Unlike congenital hepatic hemangiomas, which are most commonly solitary lesions, infantile hemangiomas are more often multifocal or diffuse. Although biopsy is not typically required to make the diagnosis, infantile hemangiomas characteristically express glucose transporter-1, an important and very specific distinguishing feature. The clinical course of infantile hemangioma is one of universal growth of the tumor up to 12 months of age, followed by gradual regression until approximately 9 years or age.

Infantile liver hemangiomas and congenital liver hemangiomas of involuting types may be observed without treatment in asymptomatic individuals. Although asymptomatic infants may be observed, the prognosis is poor in untreated infants presenting with heart failure, with an estimated 80% to 90% mortality. For patients with significant clinical manifestations, such as CHF and hypothyroidism, propranolol 1 to 3 mg/kg per day has become the mainstay of therapy and has been reported to be effective for hepatic infantile hemangiomas. There is no evidence that any pharmacotherapy accelerates the regression of rapidly involuting congenital hemangioma lesions. In the past, corticosteroids and interferon-α were recommended, but their use has been supplanted by propranolol due to its greater efficacy and lower side-effect profile. Transcatheter embolization (TCE) may be occasionally required to control severe symptoms until propranolol or time result in sufficient regression. Anatomically, these liver neoplasms may possess hepatic arterial supply, as well as extrahepatic arterial supply via the superior mesenteric, phrenic, renal, or intercostal arteries. In addition, portal venous supply may also exist and has been correlated with increased likelihood of CHF. A clear understanding of the vascular anatomy is necessary to carry out an effective embolization. Surgical hepatic artery ligation is now rarely used. Similarly, surgical resection is only rarely required, and liver transplantation is reserved for patients with abdominal compartment syndrome for whom there may not be time to allow for spontaneous or pharmacotherapy-assisted regression.

Hepatic Arteriovenous Malformations

Hepatic AVMs are much rarer than hepatic hemangiomas and have no potential for spontaneous regression. Congenital hepatic AVMs are typically localized in a single lobe of the liver and present in neonates with hepatomegaly, anemia, CHF, or portal hypertension. Hepatic AVMs are differentiated from hepatic hemangiomas by the usual presence of multiple skin hemangiomas in the latter. In hepatic AVMs the presence of pulsatile venous tracing on Doppler ultrasound is typical. Mortality from untreated hepatic AVMs is approximately 50%. Pharmacologic management of hepatic AVMs is limited to therapies aimed at supporting adequate cardiac output and anticongestive therapy using diuretics. Percutaneous embolization of congenital hepatic AVMs has become the mainstay of therapy. Embolic agents such as alcohol and N-butyl cyanoacrylate should be aimed at the central nidus to maximize effectiveness; coils and vascular plugs cannot reach the nidus and thus occlude only the feeding arteries, which predisposes to rerecruitment and recurrence of the AVM.

Hepatic AVMs associated with a predisposing syndrome such as HHT (also known as Osler-Weber-Rendu syndrome) are usually asymptomatic in children but become more commonly symptomatic in adulthood. HHT will be discussed further in the section on pulmonary AVMs.

Arterioportal Fistula

APF represents an abnormal communication between a systemic artery and a splanchnic vein. APF was first reported by Goodhart in 1889 and Sachs in 1892. Acquired APF are most common; they can occur due to tumor invasion or cirrhosis or as a result of penetrating liver trauma and can also be iatrogenic following liver biopsies and percutaneous transhepatic vascular access. Most acquired APFs have been reported in adults, and treatment by transcatheter arterial embolization is performed to reverse portal hypertension, ascites, and variceal bleeding.

Germane to this textbook are the rarer congenital APFs. These may present with sequelae of portal hypertension and/or CHF and occasionally with cyanosis. Some APFs may have an underlying congenital cause and yet not be present at birth; these include syndromes that predispose to arterial aneurysms (e.g., Ehlers-Danlos syndrome) with subsequent aneurysmal rupture into an adjacent portal vein or syndromes associated with the development of liver AVFs (Osler-Weber-Rendu syndrome, also known as HHT). These cases, despite a congenital predisposition, are better classified as acquired APFs. Truly congenital (i.e., present at birth) APFs are very rare and can be classified according to their location: intrahepatic or extrahepatic. Congenital intrahepatic APF may exist in a single lobe of the liver or in both lobes and may receive exclusive hepatic arterial supply or additional arterial supply from other arteries. In addition, a venous varix may exist at the site of the draining portal vein or umbilical vein. It has been suggested that the occurrence of CHF in congenital APF is linked to the presence of a patent ductus venosus: it is presumed that the ductus venosus provides a low-resistance path for blood flow into the right heart, whereas in the absence of a ductus venosus flow through the APF must necessarily flow subsequently through the hepatic parenchyma which may serve to limit shunting by posing an additional resistance to flow. In neonates and infant presenting with severe heart failure, the presence of an atrial communication or arterial duct may allow right-to-left shunting resulting in cyanosis. Congenital APFs presenting in adulthood with symptoms related to portal hypertension have also been reported.

TCE has been advocated as the treatment of choice given that selective surgical ligation of the feeder artery may be difficult, especially in deep intraparenchymal lesions. However, reports of successful treatment of congenital APF are rare.

Arteriovenous Fistula Involving the Umbilical Vein or Ductus Venosus

Hartung et al. reported on two cases of AVFs presenting in utero with fetal hydrops, one consisting of a tortuous artery arising from the aorta and the other consisted of a branch of the hepatic artery, both entering the umbilical vein directly. Both cases had trisomy 21, and both suffered in utero demise. Postnatal descriptions of similar fistulas are rare but illustrate the ability to successful ligate these vessels to control the shunt. Rarer still are direct communications between and umbilical artery and the umbilical vein. Such a case was described by Berg in a fetus with trisomy 18 and tetralogy of Fallot, and the AVF was associated with the development of a calcified aneurysm of the umbilical vein. A rare case of umbilical AVF detected in an infant was successfully ligated with good long-term outcome.