Osler-Weber-Rendu syndrome (OWR), also known as hereditary hemorrhagic telangiectasia, is an autosomal dominant disorder with an incidence of 1/8,000 to 1/5,000. Three mutated genes in OWR have been identified: endoglin, ACVRL/ALK1, and SMAD4 [1]. However, the mechanism by which molecular abnormalities lead to vascular lesion formation remains unclear. Mutations in the endoglin and ACVRL1 genes encoding transforming growth factor-β (TGF-β) signaling proteins in endothelial cells and TGF-β signaling pathways also characterize several familial aneurysm syndromes [2]. OWR is diagnosed if three of the following four clinical diagnostic criteria (Table 1): recurrent and spontaneous epistaxis, mucocutaneous telangiectasias, visceral arteriovenous malformations (AVMs), and a first-degree family history of OWR [3]. OWR is characterized by recurrent epistaxis, mucocutaneous or visceral telangiectasias, and AVMs of the lungs, liver, brain, and gastrointestinal tract [4]. AVMs can cause serious complications such as hypoxemia or hemorrhage in patients with pulmonary AVMs. Cerebral AVMs can lead to headaches, seizures, ischemia, or devastating hemorrhage, while liver AVMs can lead to high-output heart failure, portal hypertension, or biliary disease. The prevalence of hepatic involvement in OWR has been estimated to be 41% to 78% [5]. In most cases, intrahepatic vascular malformations occur because of shunting from the hepatic artery to the hepatic veins. The high liver output generated by these fistulae is considered to be the main cause of arterial aneurysms in the celiac vasculature of these patients [6]. This complication is rare but life-threatening if the aneurysm ruptures.

Table 1 . Diagnostic criteria of OWR (Curaçao criteria).

Criteria	Definition
Epistaxis	Spontaneous, recurrent nosebleeds
Telangiectasias	Multiple telangiectasias at characteristic sites (lips, oral cavity, fingers, nose)
Family history	A first degree relative with OWR
Visceral lesions	Any of the following: cerebral AVM, spinal AVM, pulmonary AVM, hepatic AVM, gastrointestinal telangiectasia (with or without bleeding)

The diagnosis of OWR is definite if 3 criteria are present; possible or suspected if 2 criteria are present; or unlikely if fewer than 2 criteria are present..

OWR, Osler-Weber-Rendu syndrome; AVM, arteriovenous malformation..

Hepatic artery aneurysms (HAAs) are the second most common type of visceral artery aneurysm [7]. HAAs have been reported at a rate of 0.1% to 10% during autopsies [8]. They are increasingly detected incidentally in imaging studies. Most cases are asymptomatic; however, in cases of rupture, mortality rates are high owing to the lack of tamponade. The risk of rupture is high in women and non-atherosclerotic patients [9]. Rupture-associated mortality rates range from 20% to 80% [10]. Anatomical variations of the celiacomesenteric vasculature are common, and the most common variation in Michel classification is that the right hepatic artery originates from the superior mesenteric artery (SMA) [11]. Treatment of true HAAs is indicated in aneurysms >2 cm in diameter, with progressive enlargement on follow-up imaging, and in symptomatic patients [12].

In this case report, we present the endovascular treatment of a patient with OWR and an aberrant right HAA originating from the SMA using coil embolization and stent grafting.

The present study is a case report, and according to our state’s Institutional Review Board (IRB), case reports do not require IRB approval. Written informed consent was obtained.

A 60-year-old female patient presented with mild right upper quadrant pain for 6 months and recurrent epistaxis for 4 years. The patient had no history of trauma. The patient had a family history of epistaxis. A physical examination revealed telangiectasia of the oral mucosa. Abnormalities were detected in laboratory findings at the time of admission: red blood cell count, 385×10⁶/µL; thrombocyte, 384×10⁶/µL; hemoglobin, 8.6 g/dL; hematocrit, 31.7%; low mean cellular volume, 82.3 fl; serum iron, 20 µL/dL; transferrin saturation, 7.8%; total iron-binding capacity, 237 µL/dL. Hepatic function tests showed elevated γ-glutamyl transpeptidase (58 IU/L), whereas alkaline phosphatase (107 IU/L), aspartate aminotransferase (19 IU/L), alanine aminotransferase (20 IU/L), and bilirubin were within the normal range. In addition, kidney function test and urinalysis results were within the normal range. Abdominal radiographic findings were unremarkable. Abdominal ultrasound (US) showed hepatomegaly, patch-type heterogeneity of the liver parenchyma, enlarged intrahepatic arterial vasculature, and a 49-mm diameter cystic lesion in the right upper quadrant near the hepatic hilus connected to the SMA. Color Doppler US revealed a pulsating wave accompanied by turbulent flow in the cystic lesion, suggesting an aneurysm (Fig. 1). After detection of the vascular aneurysm, thoracoabdominal computed tomography angiography (CTA) was performed to detect other vascular pathologies. On CTA, a 5 cm in diameter fusiform aneurysm of the right hepatic artery arising from the SMA was observed, with no contrast extravasation (Fig. 2). Hepatomegaly with parenchymal heterogeneity was also detected in CTA. The enlarged distal segment of the right hepatic artery and early contrast enhancement of the hepatic veins suggested an arterio-venous fistula in liver segment 7 (Fig. 3A). At the thoracic level of the CTA scan, there was a 2-cm diameter bi-lobular nodular lesion with contrast enhancement accompanied by enlarged vascular structures at the middle segment of the right lung, suggesting a pulmonary AVM (Fig. 3C, D).

Figure 1. Abdominal ultrasound showed that cystic lesion at right upper guadrant near hepatic hilus with connection to superior mesenteric artery. Color Doppler examination detected turbulent flow in the cystic lesion, suggesting aneurysm.

Figure 2. Computed tomography angiography showed that, a 5 cm in diameter fusiform aneurysm of the right hepatic artery, arising from the superior mesenteric artery was seen (arrows showed aneuysm). Also, patchy type heterogenity of liver parenchyma was seen.

Figure 3. (A) Coronal computed tomography image showed arterio-venous fistula (arrow). (B) Axial computed tomography image showed patent portal vein (star). (C, D) Lung and mediastinal window computed tomography images showed pulmonary arteriovenous malformation (arrowheads).

After the portal vein patency was confirmed (Fig. 3B), treatment of the HAA was planned because of the risk of rupture and the associated high mortality rate after rupture. Endovascular treatment was planned instead of open surgery because of the risk of morbidity associated with open surgery. Arterial access was provided through the right femoral artery using a 7F-sized vascular sheath (Shunmei). 5,000 IU of heparin was administered through the vascular sheath. An abdominal aortogram was obtained using a 5F Pigtail catheter (AngioDynamics). As the SMA angle was unsuitable for femoral intervention, brachial access was provided with a 7F-sized vascular sheath. Selective cannulation of the SMA was performed using a 0.014 guidewire (HI-TORQUE WHISPER ES Guide Wire; Abbott) and a 5F Cobra glide catheter (Terumo). Aortic angiography showed a 5 cm in diameter fusiform non-ruptured aneurysm of the right hepatic artery with an anomalous origin from the SMA. The left hepatic artery originated from the celiac artery. A 5F Cobra glide catheter was inserted into the right hepatic artery. A tip of a 2.7F microcatheter (Terumo) was coaxially placed into the HAA through a 5F catheter. Multiple 10-18 mm×20-40 cm detachable helical coils (Interlock-35; Boston Scientific) were then packed within the aneurysm. Because the aneurysm was adjacent to the origin of the hepatic artery from the SMA, a 7×38 mm stent graft (Atrium V12 Advanta; Getinge) was placed in the SMA to prevent migration of the coils to the SMA (Fig. 4). An Angio-Seal VIP vascular closure device (Terumo) was used to achieve hemostasis of the puncture sites.

Figure 4. (A) Superior mesenteric artery (SMA) angiogram showed a 5 cm in diameter fusiform non-ruptured aneurysm of right hepatic artery with anomalous origin from the SMA. (B) Digital subtraction angiogram of SMA after treatment showed multipl coils in aneuysm and no contrast media filling. Also, SMA and its other branches were normal contrast filling.

Postprocedural aspirin (100 mg/day) and clopidogrel (75 mg/day) were prescribed for 3 months, and clopidogrel was continued depending on the patient’s response. Liver function test values remained normal, and no clinical signs of bile duct or gallbladder ischemia were observed early or late after coil embolization. There were no early complications due to the procedure; however, after 2 months, her epistaxis attacks increased because of her antithrombotic medication. The initial clopidogrel medication was revised to 75 mg every two days. During the 6-month follow-up period, epistaxis attacks decreased.

Our patient initially complained of mild abdominal pain and epistaxis for 4 years. Using ultrasonography and CTA, we detected an AVM in the right lung and a large right HAA. The diagnosis of OWR can be established based on three or more of the following clinical features: recurrent and spontaneous epistaxis, mucocutaneous telangiectasias, visceral AVMs, and a first-degree family history of OWR [3]. In the present case, the patient was diagnosed with recurrent epistaxis, a family history of nasal bleeding, telangiectasias in the oral mucosa, a pulmonary AVM, and a HAA. Congenital HAAs have been reported in Marfan syndrome, Ehlers–Danlos syndrome, and OWR [13]. The frequency of developing a hepatic vascular lesion in OWR is approximately 8% to 31%, and arteriovenous shunt and AVM are known as the most common hepatic vascular lesions [14]. Moulinet et al. [15] found a higher frequency of visceral aneurysms in patients with OWR than in controls. HAAs associated with OWR have been described previously [16,17]. Aneurysms have been observed in the common hepatic artery in previously reported cases of OWR, and most cases had a normal anatomical structure. Peinado Cebrián et al. [18] presented a case of an OWR with a giant symptomatic aneurysm of the main hepatic artery with an aberrant origin in the SMA, which was very similar to our case. The difference in this case was that the authors used hybrid (surgical and endovascular) treatments for their case.

According to the Society of Vascular Surgery (SVS) clinical practice guidelines, in patients who are thought to have HAA, CTA is recommended as a diagnostic tool, and in patients with HAA who are considered for intervention, mesenteric angiography for preoperative planning is recommended. In the same guidelines, it is recommended that all symptomatic HAAs, regardless of size, and asymptomatic patients with >2 cm size or an enlargement rate of >0.5/year need to be treated. If anatomically feasible for maintaining arterial circulation to the liver, endovascular-first approach is recommended; however, in patients with extrahepatic aneurysms, open and endovascular techniques are recommended as treatment options for HAAs [12]. Rupture rates were reported in a wide range between 14% to 80% in different studies [13,19]. It has been reported that multiple HAAs and HAA with non-atherosclerotic origin are associated with a high risk of rupture [13]. According to the SVS guidelines, long-term results between open and endovascular repair are similar, but open repair has a higher morbidity than endovascular repair [12].

In the present case, early treatment was considered because of the high risk of rupture owing to the size of the aneurysm. After portal vein patency was evaluated, the right HAA of the SMA origin was treated using coil embolization and stent graft placement. There were no early complications due to the procedure; however, after 2 months, her epistaxis attacks increased because of her antithrombotic medication.

In conclusion, giant HAAs could be present in patients with OWR, and these aneurysms can be successfully treated endovascularly despite variations in their origins, as in the present case. However, stent graft placement should be reconsidered because of the need for antithrombotic medication, which may increase the incidence of epistaxis attacks in this patient group. Depending on the clinical follow-up of this cohort of patients who received stent grafts, the standard antithrombotic medication protocol may need to be modified.

The authors have nothing to disclose.

The authors have nothing to disclose.

Concept and design: MBÇ, MG. Analysis and interpretation: ÖFKK, TÖ. Data collection: MBÇ. Writing the article: MBÇ, MG. Critical revision of the article: MG, TÖ. Final approval of the article: all authors. Statistical analysis: none. Obtained funding: none. Overall responsibility: MBÇ.