Life-Threatening Esophageal Variceal Hemorrhage in a 7-Year-Old Boy with Massive Portal Vein Enlargement Due to Congenital Arterioportal Fistula

Introduction

Arterioportal fistulas (APFs) are abnormal connections between the systemic arterial system and the portal venous system, bypassing the systemic venous system entirely [1,2]. Acquired APFs can result from liver conditions like cirrhosis and hepatocellular carcinoma, or non-cirrhotic causes such as schistosomiasis and hereditary disorders, including Ehlers-Danlos syndrome. APFs may also arise from medical procedures, trauma, or hepatic artery aneurysm rupture. Congenital APFs are rare, accounting for less than 10% of cases, with an incidence of 1 in 100 000 live births [1–3]. Clinical signs of APF include portal hypertension (PH), presenting as gastrointestinal bleeding, splenomegaly, hepatomegaly, ascites, abdominal bloating, right upper-quadrant pain, and a vascular bruit over the liver. Growth disturbances may occur in children [1,2,4–6]. Symptom severity depends on factors such as fistula size, blood shunt volume, flow rate, and intrahepatic resistance [2,4–8]. About 75% of cases show symptoms by age 2 years [1]. Digital subtraction angiography (DSA) is the criterion standard for diagnosing APFs, providing both diagnostic clarity and the potential for immediate therapeutic intervention, but it is an invasive procedure. Computed tomography angiogram (CTA) and magnetic resonance imaging (MRI) are valuable for detecting early arterial phase changes in APFs and the portal vein (PV), as well as for identifying associated liver abnormalities. Color Doppler ultrasound (CD-US) is a more accessible diagnostic modality, capable of revealing altered flow patterns and turbulence within the PV [4,7,9]. APFs must be distinguished from other hepatic conditions, such as small cystic lesions, inhomogeneous areas, vascular masses like arteriovenous malformations, cavernous hemangiomas, metastatic tumors, and hepatocellular carcinoma, particularly in cirrhotic patients [1,6,9]. Embolization is currently regarded as the most effective and safest treatment option, offering rapid recovery. In cases where embolization is unsuccessful, alternative surgical approaches should be considered, including arterial ligation, partial hepatectomy, or liver transplantation [5,9,10]. This case report details an APF that remained asymptomatic for over 7 years postnatally. However, following an infection, the patient developed life-threatening complications, including massive esophageal variceal bleeding, as confirmed by esophagogastroduodenoscopy (EGD) and CTA imaging.

Case Report

The patient, a 7-year-old cachectic boy with no other past medical history, was admitted to the pediatric gastroenterology clinic due to chronic diarrhea lasting 3 weeks prior to hospitalization, along with epigastric abdominal pain, weight loss, and a lack of appetite. Liver enzyme levels, including AST, ALT, and GGT, were within normal limits. Clostridium difficile infection was confirmed by a positive A/B toxin test, and the patient was treated with antibiotics including metronidazole (4×150 mg), meropenem (3×800 mg), piperacillin-tazobactam (4×2 g), and vancomycin (2×100 mg). Additionally, antifungal therapy with fluconazole (1×120 mg) was administered. Despite these treatments, the patient’s condition deteriorated 4 days after admission, leading to severe anemia and hemorrhagic shock, which necessitated the use of norepinephrine at a dosage of 0.05–0.1 μg/kg/min. This prompted further evaluations, including an EGD under general anesthesia and a CTA of the abdomen, which confirmed the presence of bleeding esophageal varices resulting from significant PH caused by the arteriovenous fistula APF (Figure 1A, 1B). Additionally, a significant dilation of the left PV branch, measuring 47 mm, was observed. Liver function tests showed a slight deterioration from the normal values recorded at admission: AST increased from 28.0 U/L to 45.0 U/L, ALT from 9.0 U/L to 15.0 U/L, and GGT from 26.0 U/L to 47.0 U/L on the day of hemorrhagic shock. The patient was transferred to the intensive care unit, where intensive treatment was initiated, including the administration of blood products, albumin preparations, fluid therapy, and continued antibiotic therapy. High-frequency oscillatory ventilation was required for 4 days. Due to the life-threatening nature of the bleeding, the patient underwent emergency embolization of the APF in the radiology department. During general anesthesia, the following devices were inserted through the femoral artery using a 4F VERT Impress 100 cm 0.038-inch catheter. Angiography was performed through this catheter, and various microcatheters, including the LANTERN Delivery Microcatheter Straight Tip, LANTERN Delivery Microcatheter 45°, Headway DUO 156, and Headway 17 Advanced Straight Microcatheter 150 cm/11 cm; they were inserted through it as needed. The celiac trunk and common hepatic artery were selectively catheterized. Angiograms revealed a massive APF between branches of the right hepatic artery in the region of liver segment IV and a left branch of the PV. A significant dilation of the left upper branch of the PV to 47 mm was observed. Four branches of the hepatic artery supplying the APF were selectively occluded. The first devices deployed were the embolization coils (Penumbra Packing Coil) and vascular plugs (MVP-7Q Microvascular Plug System, Medtronic), which are detachable coils and occlusion devices that can be removed if needed, such as when they are undersized. These types of devices are considered relatively safe due to their low likelihood of migration once implanted. Despite their use, the APF persisted, prompting the team to escalate the treatment approach. To achieve more effective occlusion, peripheral embolization coils (MWCE-35-14-4-NESTER, Packing Coil) were employed. Additional microcoils (Penumbra SMART COIL SOFT, Penumbra SMART COIL WAVE EXTRA SOFT) were then used to pack the fistula further and enhance vessel occlusion. To ensure complete closure of the fistula, liquid embolic material (EasyX; 4 47 MV Liquid Embolic) was applied, along with Glubran tissue adhesive, to securely fill any remaining spaces between the previously implanted coils. This step was critical in sealing the fistula entirely and preventing any residual blood flow through it. Final angiographic imaging confirmed the successful occlusion of the APF, with no further leakage observed. (Figure 2A–2 C).

Following the procedure, the patient returned to the intensive care unit, where he remained for another week until his vital signs, including liver function, stabilized. He was then transferred to the pediatric surgery clinic for continued treatment. A follow-up ultrasound examination 7 days after the procedure revealed a structure with characteristics of an organizing thrombus, measuring 43×34×56 mm, with visible echoes of embolization materials at the edge. The diameter of the PV had decreased to 12 mm. Pulsatile flow was absent, with a Vmax of 58/22 cm/s, and the pulsatility index (PI) was 4.99. The spleen measured over 120 mm in length, and no free fluid was detected in the peritoneal cavity (Figure 3). In a follow-up examination 19 days after the procedure, the thrombus had reduced in size to 19×22×45 mm, the Vmax in the PV had decreased to 22/20 cm/s and the PI to 1.04, and the spleen had shrunk to less than 100 mm (Figure 4). This reduction of spleen size was attributed to decreased pressure in the portal system due to the effective closure of the APF (Figure 5A, 5B). During the hospitalization, the patient received multiple transfusions, including 3 units of irradiated leukocyte-depleted red blood cell concentrate, 1 unit of fresh frozen plasma, 1 unit of irradiated leukocyte-depleted platelet concentrate, and 20% albumin. Sedatives, analgesics, antihistamines, hemostatic agents, diuretics, proton pump inhibitors, and other supportive therapies were also administered. After 2 weeks of hospitalization and completion of antibiotic therapy in the surgical ward, the patient was discharged in good general condition with recommendations for follow-up care, including a CD-US examination. At the 10-month follow-up after surgery, the patient reported no problems, and physical examination and laboratory tests showed normal liver function. A follow-up CD-US examination revealed no thrombus. In the left liver lobe, an area of fibrosis measuring 16×16×14 mm was visible, a remnant of the closed fistula, confirming the effectiveness of the endovascular treatment. The Vmax in the portal vein was 20 cm/s, while the PI was 0.78 (Figure 6A, 6B). To the best of our knowledge, this is the only reported case where a direct correlation between infection and the behavior of an APF has been demonstrated. However, the impact of infection on dialysis fistulas has been widely documented, with reported consequences including an increased risk of thrombosis due to pathogen-induced activation of the coagulation system and a heightened risk of sepsis due to the interconnection of the arterial and venous systems [11]. As evident in this case, infection can also lead to a sudden exacerbation of PH symptoms.

Discussion

The primary goal of this case report is to describe managing complications from a primary Clostridium difficile infection and its effect on PH caused by an APF. These complications included hemorrhagic shock from esophageal variceal bleeding, triggered by an infection-related increase in PH. The case is unique due to the giant PV enlargement and the sudden onset of life-threatening symptoms from an undiagnosed APF. Congenital APFs are extremely rare; Taher et al reported 45 cases, while Cao et al found 2 congenital cases in a study of 97 cases [2,7]. The clinical manifestations of APFs vary with age. In adults, APFs are typically associated with iatrogenic trauma or focal liver lesions. Symptoms arise from the APF leading to portal PH by creating a direct connection between an artery and the PV, allowing arterial blood to enter the portal system. This increased blood flow elevates pressure within the PV, as the liver cannot sufficiently dissipate the excess flow [12]. Slow-flow fistulas often do not cause significant PH and require only periodic follow-up. Common adult symptoms include abdominal distension and pain [6,7]. In contrast, congenital APFs in children typically present symptoms by age 2 years, although late and rapid symptom onset can occur, as seen in our case. A key symptom in older children is slow development due to hypoalbuminemia, fat malabsorption, and protein-losing enteropathy. PH caused by an APF can lead to mucosal congestion in the intestines, increasing the permeability of the gut wall and causing proteins to leak into the gastrointestinal lumen [5,13]. Despite this, liver enzyme levels often remain normal, as reported in most cases [4–6,8]. Our case is notable for maintaining normal liver enzyme levels throughout the monitoring period, with only slight worsening observed during the exacerbation. No cases of spontaneous APF closure have been reported [1,8]. Symptoms onset in older children can be rapid and life-threatening, characterized by growth disorders, chronic diarrhea, and vomiting, as noted by Norton et al [5]. On DSA, APFs present as the filling of the PV with contrast medium during the arterial phase after contrast injection [7]. On CTA, APFs appear isodense on non-contrast scans. In dynamic contrast-enhanced CTA, early filling of the PV and the APF with increased arterial flow can be observed within 20–30 seconds after contrast injection. The liver segments supplied by the shunt typically exhibit hyperdense, sometimes triangular-shaped, with attenuation. If portal venous flow remains hepatopedal, these hyperattenuated segments become isodense with the liver parenchyma during the portal venous phase, approximately 30–45 seconds after injection, due to the “normal” blood supply from the splenic and mesenteric veins [7,12,14]. In ultrasonography, 6 distinct diagnostic criteria can identify an APF [6]:The artery and vein appear as closely positioned, wide, anechoic circles.The vein exhibits aneurysmal dilation.A dilated arterial branch is connected to the aneurysm, while other arterial branches remain unaffected.Ultrasound shows a visible connection between the artery and the vein.CD-US reveals turbulent flow within the aneurysmal dilation, with an arterial flow pattern detectable in both vessels.The vein demonstrates retrograde flow that has become arterialized.

When an APF is highly suspected, a lesion size >1 cm and an arterial resistive index <0.5 can confirm this suspicion [15]. Prompt treatment of APFs in children is crucial to prevent life-threatening complications. Management options for APFs include embolization, hepatic artery ligation, partial hepatic re-section, or even liver transplantation. Embolization is considered an effective and safe method; however, performing angiography in newborns carries a risk of access artery thrombosis [1,5,8]. Significant complications of embolization can include liver infarction or systemic coil migration. In the case of hepatic infarction, obstruction of arterial blood supply to healthy tissue can lead to necrosis, with an incidence rate of up to 16%. In severe cases, this may require partial organ removal, depending on the extent of the necrosis [16]. Additionally, if coils are used as the embolic agent and are improperly placed, they may migrate, potentially resulting in serious conditions such as stroke or pulmonary embolism [17]. Hepatic artery ligation is used to reduce blood flow to the APF and decrease PH, particularly when multiple embolization attempts fail. Partial hepatic resection involves removing the affected portion of the liver to excise the abnormal vascular malformation, as typically recommended for localized lesions without significant hemodynamic changes. In severe intrahepatic APF cases, where other treatments have failed or are not viable, liver transplantation may be considered, replacing the diseased liver with a healthy donor liver [3]. Treatment of APFs generally yields positive results, including resolution of PH symptoms, normalization of liver parameters, and correction of growth disorders [2]. In our case, post-treatment outcomes were favorable, with no reported symptoms or problems. An important factor for successful APF embolization is thrombosis in the periphery of the portal system. In our case, significant PV enlargement and thrombus formation were associated with embolization, leading to a reduction in PH symptoms while maintaining hepatic blood flow and organ function. Kim et al analyzed patients with PV thrombosis following embolization and found that 7 out of 12 were clinically asymptomatic, while the remaining patients exhibited symptoms of PH. Additionally, the cases they described included thrombosis of the lower limbs and significant deterioration in liver function parameters [4]. Long-term anticoagulant therapy remains a topic of discussion, as it aims to close the fistula but may hinder complete closure. This is particularly relevant for large fistulas >45 mm [1,4,5]. The authors also noted the potential recurrence of APF symptoms due to recanalization or the formation of thrombosis in the portal system over time [5,6,8]. Therefore, long-term patient follow-up is essential. As demonstrated in our case, CD-US is well-suited for this purpose, being both cost-effective and non-invasive.

Conclusions

This case underscores the critical importance of early diagnosis and intervention in managing congenital APF in pediatric patients. The severe esophageal variceal bleeding, resulting from the exacerbation of PH in a 7-year-old boy, which was precipitated by a Clostridium difficile infection, highlights the serious complications that can arise from APF. The effectiveness of endovascular treatment for large APFs was clearly demonstrated, leading to significant clinical improvement. Moreover, in our opinion, the optimal approach for APF diagnosis and follow-up appears to be the diagnostic algorithm for suspected congenital APF starting with an initial CTA and CD-US, followed by DSA with potential intervention upon confirmation, and monitoring treatment effects with CD-US.