Development of Hepatocellular Carcinoma in Type IB Abernethy Malformation

ABSTRACT

Abernethy malformation, a congenital extrahepatic portosystemic shunt, allows portal venous blood to bypass the liver and has been shown to predispose patients to hepatic tumors. We present a 29-year-old man with Type IB Abernethy malformation diagnosed in infancy who developed hepatocellular carcinoma in a noncirrhotic liver. Surgical resection, the standard curative therapy, was not feasible due to complex vascular anatomy, and he was treated with stereotactic body radiation therapy. Post-treatment imaging demonstrated sustained improvement. This case highlights the malignant potential of congenital portosystemic shunts and the importance of long-term surveillance.

INTRODUCTION

Abernethy malformation, or congenital extrahepatic portosystemic shunt (CEPS), is an uncommon developmental anomaly first described by John Abernethy in 1793. In this condition, portal venous blood diverts from the liver and drains into the systemic venous system through a complete (Type I) or partial (Type II) shunt.¹ Type I lesions are subdivided into Type IA, where the superior mesenteric and splenic veins drain separately into systemic veins, and Type IB, where they merge to form a short portal trunk that connects directly to the inferior vena cava. The estimated incidence is approximately 1 in 30,000–50,000 people.¹

Abernethy malformation is associated with a spectrum of complications including cardiac malformations such as septal defects, patent foramen ovale and valvular regurgitation, as well as both benign and malignant hepatic tumors.² Although most cases are recognized during childhood, some patients remain clinically stable until adulthood, when complications such as hepatocellular carcinoma (HCC) emerge. We present a young adult man with Type IB Abernethy malformation diagnosed in infancy who developed HCC in a noncirrhotic liver.

CASE REPORT

A 29-year-old man with a known history of Type IB Abernethy malformation diagnosed in infancy presented with right flank and abdominal pain, which was believed to be from nephrolithiasis, which he has had recurrent episodes of. His medical history included congenital heart disease (ventricular septal defect and aortic stenosis, which was repaired), left ureteral reflux with destruction of the left kidney, developmental delay, and bipolar disorder. He did not drink alcohol, use tobacco or use illicit drugs, and had no prior hepatic disease.

A computed tomography (CT) scan performed to evaluate his flank pain incidentally revealed a hepatic mass (Figure 1), prompting further workup. On examination, he was hemodynamically stable with mild right upper-quadrant tenderness. Laboratory testing showed mild transaminase elevations (aspartate aminotransferase 46 U/L, alanine aminotransferase 53 U/L) with normal bilirubin and alkaline phosphatase. Alpha-fetoprotein (AFP) was normal at 1.6 ng/mL, and carcinoembryonic antigen (3.9 ng/mL) and carbohydrate antigen 19-9 (1.0 U/mL) were within reference ranges. Viral hepatitis evaluation was negative, including hepatitis B surface antigen, hepatitis B core antibody, and hepatitis C antibody. Alpha-1 antitrypsin level was normal. There was no clinical or laboratory evidence of chronic liver disease.

Figure 1.

Axial contrast-enhanced computed tomography of the abdomen in liver window demonstrating a hepatic mass within the right hepatic lobe on the original diagnostic study.

Initial contrast-enhanced CT of the abdomen showed a 5.9-cm low-attenuation mass in the right hepatic lobe and a smaller 2.5-cm focus in the left lobe (Figure 1). Repeat CT with intravenous contrast demonstrated a 7.3 × 5.2-cm arterially enhancing lesion in segment VIII with venous washout, consistent with HCC. Vascular anatomy confirmed a Type IB Abernethy malformation, in which the portal vein drained directly into the inferior vena cava without intrahepatic branches (Figure 2).

Figure 2.

(A and B) Portal venous phase axial computed tomography demonstrating an Abernethy malformation Type IB, in which the superior mesenteric vein and splenic vein converge to form a short extrahepatic portal venous trunk that drains directly into the inferior vena cava. The intrahepatic portal venous system is congenitally absent, and the liver is entirely bypassed by portal flow that would normally enter a developed portal circulation.

MRI of the abdomen confirmed a solitary right hepatic mass measuring 6.7 × 4.9 × 6.7 cm, showing heterogeneous enhancement and no evidence of cirrhosis (Figure 3). Diagnostic laparoscopy revealed a smooth noncirrhotic liver without ascites. Although elastography was not performed, intraoperative inspection demonstrated a smooth, non-nodular liver, and biopsy of nontumorous parenchyma was deferred given the absence of radiographic or clinical features of fibrosis.

Figure 3.

(A) Initial follow-up coronal MRI of the abdomen demonstrating a mass within the right hepatic lobe measuring 6.7 × 4.9 cm. The image represents a coronal T2-weighted single-shot fast spin-echo sequence. (B) Axial postcontrast MRI of the abdomen obtained using a Liver Acquisition with Volume Acceleration sequence, demonstrating a hepatic mass with contrast washout on delayed imaging.

CT-guided biopsy of the right hepatic lesion showed almost entirely neoplastic tissue composed of hepatocyte-like cells arranged in sheets and cords traversed by thick-walled blood vessels (Figure 4). Some areas were cytologically bland, whereas others displayed higher nuclear-cytoplasmic ratios and focal atypia. Pseudoglandular spaces were present (Figure 4).

Figure 4.

(A) Low-power H&E stain of liver core biopsy (original magnification ×40) demonstrating disrupted lobular architecture with thickened hepatocyte plates and focal pigment deposition (arrows), consistent with early trabecular organization of well-differentiated HCC. (B) Higher-power H&E (original magnification ×200) highlighting 2- to 3-cell-thick trabeculae lacking portal tracts and bile ducts (arrows), characteristic of moderately differentiated HCC with preserved cytoplasmic eosinophilia. H&E, hematoxylin and eosin; HCC, hepatocellular carcinoma.

Immunohistochemical staining demonstrated diffuse CD34 positivity of sinusoidal endothelium. Cytokeratin 7 staining was largely negative within tumor cells, arguing against biliary differentiation, whereas focal copper accumulation was interpreted as a secondary finding related to altered hepatic metabolism rather than cholangiocytic lineage. These findings supported a diagnosis of well-differentiated HCC rather than hepatocellular adenoma or cholangiocarcinoma.

Management

The case was reviewed by a multidisciplinary liver tumor board. Although surgical resection is typically the preferred curative approach for localized HCC, it was deemed unsafe in this patient because of the complex Type IB portosystemic shunt and congenital cardiac anomalies, which posed prohibitive operative risk. After discussion with the tumor board, he was deemed to be a suitable candidate for radiation therapy.

He subsequently underwent stereotactic body radiation therapy directed to the dominant right hepatic lesion. Treatment was well tolerated, with transient fatigue and mild nausea that resolved over several weeks.

A post-treatment positron emission tomography scan demonstrated interval improvement in the hepatic lesions. On annual surveillance MRIs, there was continued decrease in size of the dominant right hepatic lesion and stability of smaller indeterminate foci (Figure 5). No new lesions developed, and hepatitis panels have remained normal on yearly follow-up. Systemic immunotherapy was not pursued given the favorable response to local therapy, preserved liver function, and absence of progressive or metastatic disease. The patient continues to do well clinically without recurrence or hepatic decompensation.

Figure 5.

Most recent surveillance MRI of the abdomen demonstration of rim-enhancing lesions within the hypertrophied left hepatic lobe, measuring up to 2.7 cm. The image represents an axial postcontrast, fat-suppressed gradient-echo sequence obtained during the portal venous phase.

DISCUSSION

Abernethy malformation represents a rare congenital bypass of portal venous flow that disrupts hepatic perfusion and metabolism. Although many patients are diagnosed early in life, tumor formation may occur decades later as a delayed consequence of abnormal hepatocellular stimulation.

Congenital extrahepatic portosystemic shunts have been increasingly recognized as a risk factor for hepatic malignancy. Benign lesions such as focal nodular hyperplasia and hepatocellular adenoma are most frequently reported. However, malignant transformation to HCC, although rare, has been described in both pediatric and adult populations. Type I Abernethy malformations, particularly Type IB lesions with complete diversion of portal flow and absence of intrahepatic portal venous branches, appear to carry a higher oncologic risk compared to partial (Type II) shunts.¹ This increased risk is thought to be driven by chronic portal hypoperfusion, compensatory arterial hyperperfusion, and prolonged exposure of hepatocytes to systemic pancreatic and gut-derived hormones.

Published cases of HCC arising in CEPS most often occur in noncirrhotic livers and may present with normal AFP levels, as observed in our patient. This highlights the limitation of serum tumor markers in this population and the importance of imaging-based surveillance. Our case adds to the limited adult literature by demonstrating that clinically stable patients with Type IB Abernethy malformation diagnosed in childhood remain at risk for malignant transformation well into adulthood, even in the absence of cirrhosis or traditional hepatic risk factors.

As discussed previously, Abernethy malformation can be associated with a variety of cardiac malformations, namely septal and valvular defects. Chronic hepatic congestion can be associated with certain mechanisms potentially leading to HCC. However, our patient did not have pulmonary hypertension or clinical evidence of chronic hepatic congestion, suggesting that complete portal diversion rather than congestive hepatopathy was the more likely culprit in this case.

There are currently no standardized screening guidelines for patients with CEPS; however, based on available case reports and series, we suggest lifelong surveillance with cross-sectional imaging. Annual liver MRI with contrast may be the most appropriate modality given the poor sensitivity of AFP and the frequent absence of cirrhosis in this population. Earlier and more frequent surveillance may be reasonable in patients with Type I shunts, associated cardiac disease, or prior hepatic lesions.

Curative treatment of HCC in patients with CEPS is often challenging due to complex vascular anatomy and absent portal venous flow. Surgical resection and liver transplantation may be technically prohibitive. In this case, significant congenital cardiac disease and complete portosystemic shunting precluded surgical intervention. Transarterial radioembolization with yttrium-90 was considered but deemed high risk given the extensive shunting and potential for extrahepatic radiation. Stereotactic body radiation therapy provided a feasible, minimally invasive alternative and resulted in positive radiographic response without complication.

This case reinforces the malignant potential of congenital portosystemic shunts and emphasizes the need for long-term surveillance and individualized management strategies in patients with Abernethy malformation.

DISCLOSURES

Author contributions: F. Ahmadi, N. Al-Saidi, V. Khanna, L. Shamban: study concept and design, analysis and interpretation of data; N. Al-Saidi and F. Ahmadi: acquisition of fata and drafting of the manuscript; V. Khanna and L. Shamban: supervision; all authors gave final approval of the manuscript. L. Shamban is the article guarantor.

Financial disclosure: None to report.

Informed consent was obtained for this case report.

ABBREVIATIONS:

AFP

alpha-fetoprotein

CA 19-9

carbohydrate antigen 19-9

CEPS

congenital extrahepatic portosystemic shunt

CT

computed tomography

H&E

hematoxylin and eosin

HCC

hepatocellular carcinoma

IVC

inferior vena cava

MRI

magnetic resonance imaging

SMV

superior mesenteric vein