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Miscellaneous Congenital and Acquired Hepatic Vascular Disorders in Small Animals


Sharon A. Center

, DVM, DACVIM, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University

Reviewed/Revised Aug 2023

Congenital hepatic arteriovenous malformations are uncommon.

Acquired vascular abnormalities recognized in dogs and cats include acquired hepatic arteriovenous fistulas and hepatic venous outflow obstruction (sinusoidal occlusion syndrome, Budd-Chiari syndrome, veno-occlusive disease), and portal venous thromboembolism.

Hepatic Arteriovenous Malformation

A hepatic arteriovenous (AV) malformation or fistula is a congenital anomalous direct intrahepatic connection between the high-pressure hepatic arterial and the low-pressure portal venous systems. Direct junction between these two circulatory circuits allows high-pressure arterialized blood to circulate directly into and then retrograde via portal vasculature, leading to intrahepatic sinusoidal and extrahepatic splanchnic portal hypertension (PH), ascites, and acquired portosystemic shunt (APSS) formation.

Less commonly, AV fistulas are acquired from trauma (ie, iatrogenic needle biopsy lesions, other trauma lesions), or develop within neoplastic lesions. When congenital, clinical signs initially manifest at a young age as inappetence, vomiting, and diarrhea (may be bloody), with episodic hepatic encephalopathy (HE) and abdominal effusion. A murmur or bruit reflecting turbulent blood flow via the AV malformation may be audible over the affected liver lobe. Rarely, an intrahepatic AV malformation represents a variant of intrahepatic portosystemic vascular anomalies (I-PSVAs).

Laboratory abnormalities are identical to those associated with more common PSVAs Portosystemic Vascular Anomalies Reduced hepatic portal venous perfusion causes characteristic histopathologic changes. The most common causes of portal venous hypoperfusion are congenital malformations impacting portal venous... read more and additionally may disclose circulating schistocytes acquired from turbulent blood flow within the lesion. Although ascites is a feature distinguishing AV malformations from a typical PSVA, clinical features also may be similarly encountered in dogs with severe congenital portal atresia and ductal plate malformation (DPM; congenital hepatic fibrosis phenotype).

Abdominal ultrasonography can easily identify intrahepatic AV malformations by detection of pulsating arterial flow, associated APSS using color-flow Doppler interrogation, and presence of abdominal effusion. Definitive imaging requires contrast angiography via the celiac artery or cranial mesenteric artery (former gold standard) or multisector angiographic CT, considered the new gold standard imaging modality.

On imaging, gross inspection, and histologic evaluation, multiple AV interconnections are often evident within an affected liver lobe. Although surgical lobectomy or ligation of the nutrient artery feeding the malformation is the conventional treatment, presence of additional hepatic microvascular malformations in dogs with congenital disease thwarts efficacy of simple lesion ablation. Biopsy of the liver from sites distant to the AV malformations (other liver lobes) is strongly recommended to determine presence and breadth of hepatic microvascular malformations.

Alone, surgical management has a dismal prognosis for cure in the presence of widespread microscopic vascular malformations and APSSs. Even when combined with intravascular acrylamide vascular occlusion or deployment of intraluminal thrombogenic coils, outcomes are complicated.

No procedure can guarantee clinical cure because of the potential for widespread microvascular malformations associated with these congenital anomalies and because of persistent shunting via APSSs. Described outcomes for dogs treated by surgical or interventional methods include improved clinical status without complete resolution, treatment failure, massive intraoperative hemorrhage, procedural complications (unintended embolization of nontargeted vasculature), and need for chronic medical management for continued HE.

Hepatic Vein Outflow Obstruction

Hepatic venous outflow obstruction associated with cardiac or pericardial disorders causes passive congestion of the caudal vena cava and liver (hepatomegaly) and abdominal effusion without development of APSSs. Disorders include:

  • right heart failure

  • pericardial disease causing tamponade

  • congenital defects (cor triatriatum dexter)

  • cardiac tumors

  • obstruction of the caudal vena cava (eg, postcaval syndrome associated with heartworm disease, congenital kinking of the caudal vena cava, vascular or neoplastic thrombosis of the caudal vena cava, diaphragmatic hernia compressing the caudal vena cava)

  • obstruction of the efferent hepatic venous system by liver lobe torsion or a compressive mass lesion. These lesions typically impact cranial vena cava flow and hepatic venous outflow abrogating development of stand-alone splanchnic hypertension explaining the lack of APSS formation.

Hepatic venous outflow obstruction due to disorders within zone 3 (centrilobular or perivenular hepatic cords and sinusoids) or directly involving hepatic venous vasculature include sinusoidal occlusion syndrome, Budd-Chiari syndrome, and veno-occlusive disease (VOD). The following defines specifically classified syndromes along with description of clinical and diagnostic features and interventions.

In the context of small animal patients, sinusoidal occlusion syndrome (SOS) defines severe zone 3 (perivenular, centrilobular) hepatocyte injury and sinusoidal collapse restricted to this region, abutting hepatic venules and impairing sinusoidal circulatory egress. With progressive SOS, sinusoidal collapse with fibrosis of perivenular adventitial support interrupts sinusoidal drainage angles, obscures venular profiles, and evolves prominent distended lymphatic channels associated with regional congestion.

The most common cause of SOS in dogs is as the sequela of severe copper-associated zone 3 injury with damage escalated by concurrent administration of NSAIDs or anther zone-specific hepatoinjury (eg, pyrrolizidine alkaloid rarely encountered with dogs exposed to herbal remedies, rarely evolving in dogs with chronic sepsis). However, any cause of zone 3 parenchymal collapse with necroinflammatory injury and consequent fibrosis can evolve this lesion.

Within several weeks of regional injury, accrual of occlusive extracellular matrix with fibrillar collagen deposition (confirmed with Masson trichrome staining of a liver biopsy) is observed. Another cause infrequently encountered is dogs' pathological accumulation of hematopoietic precursors (ie, agnogenic myeloid metaplasia, aberrant extramedullary hematopoiesis) that occlusively infiltrate centrilobular regions and perivenular adventitia. Once fibrosing SOS develops, the lesion is irreversible.

Pathological extramedullary hematopoiesis accumulation leading to SOS is usually not associated with fibrosis. However, it remains a stubborn process resistant to intervention if an underlying cause of progenitor differentiation cannot be identified (inspect bone marrow for leukemic or myelodysplastic infiltrates and marrow fibrosis, evaluate circulating leukocytes for neoplastic characteristics, consider inflammatory and causes for induction of granulocyte colony-stimulating factor expression).

Primary Budd-Chiari syndrome is rare and classically defined as thromboembolism of hepatic veins or closely affiliated regions of the inferior vena cava. Classically, Budd-Chiari syndrome closely is associated with a wide spectrum of prothrombotic conditions, sometimes of underlying neoplastic origin. Broader application of Budd-Chiari syndrome terminology has been applied as an umbrella classification scheme for any cause of hepatic venule and vein outflow obstruction. Herein, Budd-Chiari syndrome is defined as its classic description, and descriptions of the other disorders are separately addressed.

Detection of Budd-Chiari syndrome is by ultrasonography with color-flow Doppler that can identify absence of hepatic venule and vein profiles, perfusion, and presence of intraluminal filling defects. Imaging with CT angiography can also discriminate impeded vascular flow with underfilling (or absence of) hepatic vein or inferior vena cava perfusion. In animals surviving long enough to permit recanalization of nonneoplastic thrombosed vasculature, color-flow ultrasonography may detect regained intraluminal perfusion. Treatment involves intervention of causal coagulopathic syndromes or other underlying causes (ie, vascular or thrombotic neoplasia) and management of associated ascites.

In veterinary patients, veno-occlusive disease is histologically distinguished by obliterative compression or degeneration of hepatic venules and vein silhouettes. This lesion is most often encountered in small-breed dogs with microvascular dysplasia (MVD) with or without associated PSVA. It is more commonly identified in Yorkshire Terrier, Maltese, and Pug breeds.

Obliterative coalesced foamy macrophages (lipogranulomas) containing degenerative membranous debris display variable accumulations of lipofuscin and iron. These lipogranulomas compress, displace, or obliteratively fill the lumen of hepatic venules and veins. When observed in dogs with PSVA, this portends a poor response to shunt ligation. Collection of perivenular lipid vacuolated macrophages or hepatocytes is not consistent with this lesion; this is an obliterative venopathy.

Clinical signs reflecting passive congestion may include inappetence, lethargy, gastrointestinal signs, hepatomegaly (unless cause is associated with PSVAs or MVD), ascites, along with features related to the underlying primary disorder (eg, cardiac, pericardial, venous obstruction). Passive congestion leads to sinusoidal distention, causing hepatomegaly, modest increases in liver enzyme activities, and abdominal effusion (modified transudate).

Clinical features of hepatic venous outflow obstruction syndromes additionally may reflect development of APSSs (ie, high total serum bile acid concentrations, subnormal BUN, creatinine, cholesterol, with variable normal to low protein C activity), mild to moderate increases in hepatic transaminase activity, and variable concentrations of total bilirubin and albumin. Associated abdominal effusion is usually a modified transudate.

Thoracic and abdominal radiographs help distinguish cardiac or pericardial causes from other disorders and may reveal "kinking" or impingement of the prediaphragmatic inferior vena cava. Echocardiography defines cardiac or pericardial causes of passive congestion (eg, differentiating pericardial from cardiac causes, congenital malformations (eg, cor triatriatum dexter), or intrathoracic masses compressing the caudal vena cava.

Abdominal ultrasonography confirms hepatic venular distention in passive congestion and diminished hepatic venular flow or size in SOS, Budd-Chiari syndrome, or VOD syndrome. Treatment and prognosis depend on underlying pathologies but require liver biopsy when obvious cardiac, pericardial or vena caval impingement syndromes are excluded.

Cholangiovenous Reflux in Small Animals

Cholestatic disorders are notoriously associated with invasion of bacterial organisms or endotoxin from inoculated portal tracts.

Bacteria, bacterial toxins, or endotoxin can disseminate directly into the sinusoidal circulation or through ultralymph in the space of Disse to regional lymphatics (portal, centrilobular, and capsular), with subsequent drainage into the thoracic duct and then into the systemic circulation.

Cholangiovenous reflux is the nomenclature describing this phenomenon.

Etiology and Pathogenesis of Cholangiovenous Reflux in Small Animals

Surgical manipulation of biliary structures during decompression of an obstructed bile duct, removal of septic choleliths, cholecystectomy for septic suppurative cholecystitis, or debulking of a hepatic abscess or necrotic hepatic neoplasm (ie, large hepatocellular carcinoma) can provoke acute cholangiovenous reflux. Regurgitation of bacteria and endotoxin via bile ductules into lymphatics and sinusoids leads to acute systemic bacteremia and endotoxemia, resulting in critical illness.

Cholangiovenous reflux can materialize, especially in cats, despite pre- and perioperative antimicrobial administration, normalized hydration and electrolyte status, cautious anesthetic protocols, and expert surgical skills.

Clinical Signs of Cholangiovenous Reflux in Small Animals

Clinical signs associated with cholangiovenous reflux include weakness, collapse, and nonresponsive hypotension that can progress to acute renal failure and death.

Treatment and Prognosis of Cholangiovenous Reflux in Small Animals

Many but not all affected animals can recover with provision of critical supportive care.

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