Abernethy malformation: case report and literature review

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1. Background

Congenital portosystemic shunts (CPSS) are rare congenital anomalies associated with partial or complete diversion of the portal blood into the systemic circulation. The incidence of CPSS is estimated to be 1:30,000 births and 1:50,000 for those that persist beyond early life [7]. Classification of CPSS is complex because of the significant variability of vascular anatomy. All CPSS are generally divided into intra- and extrahepatic shunts with partial or complete portal blood deprivation [27]. Congenital extrahepatic portosystemic shunts (CEPSS) are termed Abernethy malformation, first documented in 1793 by John Abernethy [1]. However, only limited cases of CEPSS have been reported so far.

2. Case 

A 15-year-old male was admitted to the hospital with episodes of high arterial blood pressure (up to 160/90 mm Hg), recurrent nose bleeds, episodes of chest pain, dizziness, shortness of breath, low exercise tolerance, blood in the stool, vague epigastric pain and nausea and long history of itching. The patient’s medical history was limited: twelve years prior to the admission, the diagnosis of portal hypertension was established (no medical records provided).

Liver function tests showed a mild increase in alanine aminotransferase 59.8 U/L (normal range 13–50 IU/L), increased aspartate aminotransferase 67.1 U/L (15–46 IU/L); U/L), gamma-glutamyl transferase 91 U/L (2–42 U/L), alkaline phosphatase 316 U/L (52–171 U/L), total bilirubin 39.2 μmol/L (3.4–17.1 μmol/L) and direct bilirubin 12.5 μmol/L (0–5 μmol/L); albumin was slightly decreased – 40.2 g/L (41–55 g/L). Routine blood tests and coagulation studies were normal. His serum BUN and creatinine levels were also in the reference ranges.

Transthoracic echocardiogram revealed dilatation of the heart chambers, myocardial hypertrophy (left ventricular wall thickness – 1.6 cm), and systolic pulmonary hypertension (pulmonary artery systolic pressure [PASP] – 40 mm Hg). Notably, there was an aortic ectasia (diameter at the level of the fibrous ring was 3.4 cm, the sinuses of Valsalva – 5.1 cm, and the ascending aorta – 4.0 cm). No left ventricular outflow tract stenosis or ventricular wall hypokinesia were found; left ventricular function was preserved.

Abdominal ultrasound (US) showed enlarged liver with multiple nodules, changes in parenchymal structure, and signs of fibrosis. No prominent portal venous trunk or branches at the level of porta hepatis were noted. The hepatic vascular pattern was deformed with hepatic veins stenosis. Among other findings were signs of portal hypertension and moderate spleen enlargement. Additional imaging studies were performed to confirm the diagnosis and clarify the vascular anatomy.

Contrast-enhanced abdominal computed tomography (CT) with multiplanar reconstruction revealed that splenic vein (12 mm in diameter (Figure 1)) and superior mesenteric vein fused together, forming a portal vein conduit dilated to 28 mm in diameter (Figure 2,3), flowing directly into the inferior vena cava (IVC), bypassing porta hepatis (Figure 4). Moderate liver and spleen enlargement and weak heterogenous contrast enhancement of liver parenchyma were also noted. The findings were consistent with Abernethy malformation type Ib.

CT pulmonary angiogram showed no abnormal vascular shunts, but it confirmed pulmonary trunk dilatation (40 mm in diameter) (Figure 5), dilatation of the heart chambers, and myocardial hypertrophy (Figure 6).

Due to the low effectiveness of conservative treatment, severity of patient’s symptoms, and shunt anatomy, liver transplantation was recommended after multidisciplinary panel consultations. Currently, the patient is waiting for surgical intervention.

3. Discussion

Mechanisms

Etiology and mechanisms of development of congenital and acquired CEPSS differentiate significantly. Congenital CEPSSs occur due to abnormal formation or involution of fetal vasculature, while acquired shunts are secondary to liver diseases [27]. In the literature, there are two dominant theories of CEPSS formation: congenital malformations and anomalies of ductus venosus.

The development of the portal system is complex and occurs between the 4th and 10th week of embryonic life. Systemic venous system results from embryonic anterior and posterior cardinal veins. Portal venous system forms from vitelline veins, which carry blood from the yolk sac to the sinus venosus [13]. If the proper process of portal system development is disrupted, CEPSS occurs. This variant is closely associated with combined congenital pathologies. According to the study of Bernard O. et al., congenital heart disease was the most frequently observed concomitant pathology (in 45 out of 265 cases); other recorded malformations included various abnormalities of kidneys, bile ducts (including biliary atresia), digestive system, bones, and brain [7].

Another discussed mechanism is the absence of functioning fetal ductus venosus due to anatomical defect or occlusion. In a normal fetus, ductus venosus shunts the blood from the umbilical vein to the IVC, bypassing the liver. Naturally, functional closure occurs within the first minutes of birth, and structural closure takes place during the first weeks of life in most full-term neonates [8]. The umbilical vein and ductus venosus anatomically close during the first months of life and become the ligamentum teres and the ligamentum venosum, respectively [13]. Absence of functioning ductus venosus in the fetus can stimulate formation of abnormal vessels. Those abnormal vessels may persist and develop into abnormal shunts, resulting in hypoplasia of the portal venous system. Absence of ductus venosus has been reported in some cases of CEPSS [5, 12].

Classification

One of the most widely used classifications of CEPSS is the classification system introduced by Morgan and Superina in 1994 (Table 1) [23]. According to this classification, Abernethy malformation is divided into two types depending on the patency of the intrahepatic portal system. Type 1 is defined as a complete portosystemic shunt, whereas type 2 is described as partial blood shunting to systemic veins with a certain degree of portal system development (Figure 7). Different treatment options are available depending on the CEPSS type [35].

 

Type I	Liver not perfused with portal blood – total shunt
	Ia: SMV and splenic vein do not joint to form confluence
	Ib: SMV and splenic vein join to form confluence
Type II	Liver perfused with portal blood – partial shunt (eg, portal-hepatic venous anastomoses)
	IIa: congenital
	IIb: acquired

Table 1. Classification System for portasystemic anomalies by Morgen and Superina [23]

Clinical manifestations, complications

Clinical presentations are variable and depend on the ratio of blood flow through the shunt. Manifestations vary from accidental findings in asymptomatic adult patients [26, 32] to complex congenital malformations [36], severe hypoxemia [31], encephalopathy [21, 22], or liver tumors [33]. Most patients present with nonspecific symptoms such as acute hepatic decompensation or cirrhosis. According to Xue-qin Lin et al., data from 703 patients with CEPSS extracted from 451 articles revealed that the majority of the reported patients with Abernethy malformation were children or young adults under 18 years old [20]. Severe congenital pathologies with a higher degree of blood shunting are usually diagnosed at a younger age, whereas patients with partial blood shunting can remain asymptomatic till adulthood.

In the early neonatal period, galactosemia, diagnosed during routine screening, can be the first sign of CEPSS. Normally galactose is metabolized in the liver by the GALT enzyme to glucose. In children with CEPSS, galactose bypasses the liver, resulting in increased levels in systemic circulation [14, 29]. According to numerous researchers, hypergalactosemia is present in up to 70% of newborns with CPSS [7]. Other potential symptoms in the early neonatal period are growth restriction, neonatal cholestasis, and hepatic encephalopathy [28].

In patients with milder pathology, CEPSS can go unnoticed until adulthood. Presentation may be due to symptoms related to hepatic encephalopathy, liver masses, or pulmonary hypertension.

Subclinical hepatic encephalopathy is observed in up to 30% of cases with CEPSS [11]. Shunting of portal blood causes increased ammonium levels in the systemic blood flow. Blood ammonia produced in the gastrointestinal tract bypasses the liver and flows directly into the IVC. Astrocytes metabolize ammonium to glutamine, which in turn has toxic effects on the brain [21]. Hyperammonemia may present without encephalopathy, especially at younger ages. Clinical encephalopathy is more common in older patients, probably due to lower compensatory abilities [22]. Diagnosis in such cases can be difficult due to the low specificity of symptoms [2, 3, 21]. Raised serum ammonia concentration without evidence of liver cirrhosis should prompt further investigations for extrahepatic shunts.

Patients with CPSS are prone to the development of multiple liver tumors. Literature on histological changes of liver parenchyma in patients with CPSS is limited. Claudio De Vito et al. described a case series of 22 patients with CPSS, including 19 patients with CEPSS, who were diagnosed and managed in their institution over a period of 15 years [10]. According to their results, the most characteristic histological findings in peripheral liver parenchyma included presence of portal prominent thin-walled channels, arterial-biliary dyads, increased arterial profiles in the portal tracts and the lobule, and frequent lack of the physiological periportal-vacuolated hepatocytes in children.

Pathophysiology of hepatic tumor development in patients with CEPSS remains unclear. One of the discussed mechanisms is attributed to a reduction in liver regeneration abilities. Low portal blood flow leads to a decrease in the delivery of insulin and glucagon to hepatocytes, making them more vulnerable to damage and neoplasm development [17]. Also, increased hepatic arterial blood flow can be associated with parenchymal cell de-differentiation [33].

Nodular liver lesions are common findings in different types of Abernethy malformation. In most cases liver nodules are benign and include focal nodular hyperplasia, hepatic adenomas, and regenerative nodules. The majority of patients are asymptomatic, although patients can rarely present with an abdominal mass. In our case, liver nodules were also accidentally found during the abdominal US.

However, not all liver masses are benign. Type I Abernethy malformation is associated with hepatoblastoma and hepatocellular carcinoma (HCC) [9, 16]. Hepatoblastoma is a rare tumor seen in children with CEPSS. These tumors have an unfavorable prognosis. The majority of the described cases were lethal [9, 17]. Hepatocellular carcinomas more often develop in adults, though Benedict M. et al. published a case of a 12-month-old male with histologically and immunohistochemically confirmed HCC [6]. Diagnosis can be complicated as some of the reported lesions have controversial radiological features and can be mistaken for benign masses [32], biopsy is usually required. Liver transplant is one of the treatment options [25].

In some cases of CEPSS, patients present with signs of pulmonary hypertension: shortness of breath and dyspnea [19, 24]. Severe pulmonary hypertension can lead to cardiogenic syncope due to decreased preload and low cerebral perfusion [20]. In our case, pulmonary hypertension was also diagnosed.

Hepatopulmonary syndrome occurs in patients with liver disease accompanied by portal hypertension. Persistent portosystemic shunt lets vasoactive mediators from the intestine bypass hepatic circulation, flowing directly to the pulmonary vascular bed, causing imbalance between vasodilation and vasoconstriction substances, inducing pulmonary hypertension [35]. Correction of hepatic vascular anomalies is curative.

Diagnosis and treatment 

There are currently no published guidelines for the diagnosis and treatment of CEPSS. Based on the results of the multicenter international study, that included 66 patients, Baiges A. et al. propose a management algorithm for patients with CEPSS (Figure 8) [4].

In our case, Abernethy malformation was suspected on the abdominal US. In general, US signs of CEPSS include portal trunk absence or hypoplasia, solid focal lesions in liver parenchyma, deficiencies of intrahepatic portal vessels and flow signals, hepatic artery hypertrophy [30]. Anomalies identified by the US should be further confirmed with other imaging modalities, such as CT or MR angiography. Contrast-enhanced CT provides essential information about shunt size, orientation, and type, which helps to choose the most suitable treatment approach individually for each patient. It also allows to visualize and evaluate concomitant anomalies, including liver masses. MR angiography is a reliable and noninvasive modality for visualizing hepatic vascular anatomy. It is radiation-free and has better soft tissue contrast than CT. Moreover, diffusion-weighted sequences can provide additional valuable information for evaluation of nodular liver lesions and decision-making.

Therapeutic approach depends on the shunt type and size, severity of symptoms, coexisting anomalies, and related complications. Asymptomatic patients could be medically followed. Given the risks of complications development, Kwapisz L. et al. recommend for patients with CEPSS routine clinical assessments, regular blood work, including liver enzyme and liver function tests, and annual liver imaging [16].

Experience of treatment of patients with Abernethy malformation is still limited. Based on the reported cases, current treatment options include interventional or surgical shunt closure and liver transplantation. Type I long-term treatment options are limited to liver transplant with supportive therapy while waiting for surgery. Patients with Type II CEPSS have more therapeutic options depending on the developed complications and associated anomalies. It is possible to ligate or close the portosystemic shunt using interventional angiography (with coils or plugs) [34]. However, interventional closure may cause recurrent hyperammonemia, as has been reported [18].

It may be beneficial to perform a balloon shunt occlusion test to asses intra-hepatic portal system (IHPS) in patients with both types of CEPSS [18]. This test allows to visualize small portal vein branches which cannot be seen on US. Kanazawa H, et al. proposed a new IHPS classification (mild, moderate and severe types) based on the results of shunt occlusion test [15]. IHPS classification correlates with the portal venous pressure under shunt occlusion, the histopathological findings, postoperative portal venous flow and liver regeneration and is useful for decision-making whether to perform single-stage, 2-stage shunt closure or liver transplantation.

4. Conclusion

Abernethy malformation is a rare pathology associated with severe complications and poor outcomes. Due to low incidence, unspecific symptoms, involvement of different organ systems, and variable presentations, diagnosis of CEPSS is a challenge. Imaging plays an important role in diagnosis and treatment planning. Early identification and individualized treatment approach are crucial to prevent complications. Long-term follow-up and monitoring for malignancy are mandatory.

About the authors

Alexandra Panyukova

Medical Research and Educational Center, Lomonosov Moscow State University

Author for correspondence.
Email: panyukovaalexandra@gmail.com
ORCID iD: 0000-0002-5367-280X

MD, Diagnostic Radiology Resident Physician

Russian Federation, Lomonosovsky ave, 27/10, Moscow, 119991, Russia

Valentin Sinitsyn

Medical Research and Educational Center, “Moscow State University named after M.V. Lomonosov"

Email: vsini@mail.ru
ORCID iD: 0000-0002-5649-2193
SPIN-code: 8449-6590

MD, PhD, Professor, Chief of Radiodiagnostics and Radiotherapy, Faculty of Fundamental Medicine, Chair of the Department of Radiodiagnostics

Russian Federation, Lomonosovsky ave, 27/10, Moscow, 119991, Russia

Elena Mershina

Medical Research and Educational Center, “Moscow State University named after M.V. Lomonosov"

Email: elena_mershina@mail.ru
ORCID iD: 0000-0002-1266-4926
SPIN-code: 6897-9641

MD, PhD, Assistant Professor of Radiology, Chair of the Department of Radiology

Russian Federation, Lomonosovsky ave, 27/10, Moscow, 119991, Russia

Natalya Rucheva

Shumakov National Medical Research Center for Transplantology and Artificial Organs

Email: rna1969@yandex.ru
ORCID iD: 0000-0002-8063-4462

MD, PhD, Chair of the Department of Radiology

Russian Federation, Schukinskaya st., 1, Moscow, Russia, 123182

References

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