Congenital intrahepatic portosystemic shunts: a potential cause for early-onset neonatal cholestasis

Introduction

Cholestasis in the first days of life is uncommon in neonates. Neonatal cholestasis is usually associated with shock, sepsis, alloimmunity, metabolic disorders or biliary obstruction. However, when typical causes for neonatal cholestasis cannot be identified, a congenital intrahepatic portosystemic shunt should be considered. We review three cases of early-onset cholestasis resulting from a congenital intrahepatic portosystemic shunt.

Case presentations

Case 1

A term, 1685 g, male born to a 27-year-old primigravida woman. Her maternal laboratory tests were unremarkable. Her pregnancy was complicated by growth restriction, oligohydramnios and pre-eclampsia. An emergent cesarean section was performed due to fetal distress. The baby received brief face mask continuous positive airway pressure (CPAP) resuscitation, but was subsequently weaned to room air. On examination, he had bleeding at venipuncture sites and soft fetal dimorphisms (short, up-slanting palpebral fissures, small and slightly low-set ears, a supernummery nipple, short toes, small penis and a sacral skin tag). The initial platelet count was 22 k/dL and glucose was 11 mg/dL. He had elevated liver enzymes [alanine aminotransferase (ALT) 119 U/L and aspartate aminotransferase (AST)/303 U/L] and direct hyperbilirubinemia (direct 3.14 mg/dL and indirect bilirubin was 1.80 mg/dL). The lactate was 3.3 mmol/L and the arterial blood gas on admission was pH 7.38, pCO₂ 36 mm Hg, pO₂ 76 mm Hg, base deficit −3 mmol/L. Antibiotics were started. A full septic work-up including bacterial cultures, toxoplasma antibody, urine cytomegalovirus (CMV), rectal herpes simplex virus (HSV) swab and enterovirus polymerase chain reaction (PCR) were negative. His genetic work-up and newborn screen were unremarkable. He had normal urine output and his stools transitioned from meconium to pigmented during the first days of life. Due to thrombocytopenia, both the head ultrasound (US) and the brain magnetic resonance imaging (MRI) study showed a right occipitoparietal hemorrhage within the intraparenchymal, right subarachnoid and right subdural areas. This unusual bleeding pattern for a newborn was thought to be secondary to platelet dysfunction. A liver US with Doppler study was done secondary to cholestasis. The liver US with Doppler study suggested the presence of an intrahepatic portosystemic shunt between the left portal vein and left hepatic vein, with resultant dilatation of the left hepatic vein. The US was otherwise normal (see Figure 1). He was treated with fat-soluble multivitamins and ursodeoxycholic acid. The cholestasis and the intrahepatic portosystemic shunt resolved spontaneously at 1 year of age.

Figure 1:

The ultrasound images show the location of the intrahepatic portosystemic shunt in Case 1.

Panel A marks the location of the left hepatic vein (LHV) and left portal vein (LPV). Panel B depicts the interconnection between the left hepatic vein and left portal vein. Panel C shows the blood flow shunt between the LHV and LPV using color Doppler flow.

Discussion

We present three cases of neonatal cholestasis where direct hyperbilirubinemia was noted within the first days of life. All patients had an exhaustive search for the cause of cholestasis. Ultimately, liver ultrasonography with Doppler studies demonstrated an abnormal intrahepatic portovenous vascular connection. The congenital intrahepatic portosystemic venous shunt was felt to be the cause of cholestasis as other causes were excluded. In our series, both cholestasis and the shunt resolved spontaneously by 1 year of age.

Cholestasis is uncommon in the first days of life in a neonate. Cholestasis is defined as an increase in the direct component of serum bilirubin to greater than 1 mg/dL or a proportion greater than 20% of the serum bilirubin [1]. Neonatal cholestasis can present with jaundice, pale urine and/or pale stools. Infants with associated coagulopathy may present with bleeding, bruising or hematoma. Hepatosplenomegaly may also be present [1]. The differential diagnosis of neonatal cholestasis can be divided into those intrinsic and extrinsic to the liver. Intrinsic causes of cholestasis may be transient due to multiorgan dysfunction from perinatal asphyxia, congestion or infections, such as bacterial sepsis (group B streptococcus, Listeria monocytogenes and Escherichia coli), TORCHES infection (typically accompanied by other stigmata like rash, hepatosplenomegaly and microcephaly) and viral infections (such as enterovirus, cytomegalovirus, herpes simplex virus and parvovirus). Metabolic conditions (pituitary and thyroid disorders), PFIC, alloimmune liver disease, Wilson’s disease and α-1 antitrypsin deficiency also present with cholestasis. Toxin build-up from prolonged parenteral nutrition will result in intestinal failure associated liver disease, but later in life. Extrinsic causes result in obstruction of bile flow from the liver. While biliary atresia usually presents in the first 2–8 weeks of life, an embryonic variant may present at birth, as can other biliary obstructive disorders such as a choledochal cyst. Caroli disease is a congenital disorder characterized by multifocal, segmental dilatation of large intrahepatic bile ducts and is associated with renal cystic disease. Cholestasis due to Alagille syndrome is caused by a paucity of intrahepatic bile ducts, and is associated with growth impairment, cardiac abnormalities and dysmorphic facial features [1], [2].

A congenital portosystemic venous shunt results from an interconnection between the hepatic and systemic venous circulation in the absence of primary liver disease. Intrahepatic venous shunts may be formed from a large shunt vessel or hemangioma resulting from an abnormal coalescence of the vitello-umbilical venous plexus during embryogenesis [3], [4]. The ductus venosus normally disappears after a few days in term neonates and after a few weeks in premature babies [4]. The lack of complete involution of one or several of these primordial vessels may give rise to abnormal vascular communications between any vein of the portal system and any vein of the inferior vena cava system [5]. The development of these shunts probably has a genetic origin as suggested by reports of familial cases, the association of congenital portosystemic shunts with chromosomal abnormalities including Down syndrome, the frequent association with other malformations including congenital heart diseases, and polysplenia syndrome, with or without biliary atresia [6].

Park et al. [7] classified four types of intrahepatic portosystemic venous shunts. Type I is the most common type and is characterized by a single large shunt with a constant diameter that connects the right portal vein to the inferior vena cava. Type II is a localized peripheral shunt in which single or multiple communications are found between peripheral branches of the portal and hepatic veins in one hepatic segment. In Type III, the peripheral portal and hepatic veins as connected through an aneurysm. Type IV has multiple communications between the peripheral portal and hepatic veins as seen diffusely in both the lobes.

Transient neonatal cholestasis has been reported in children with congenital, extra- or intrahepatic, portosystemic shunts [6]. The risk of neonatal cholestasis is increased in the presence of a shunt that decreases the perfusion of the neonatal liver. Hepatic congestion and poor perfusion can lead to elevated aminotransferases and hyperbilirubinemia – although more commonly an indirect hyperbilirubinemia. Poor perfusion may also result in bacterial translocation across the intestinal mucosa and production of inflammatory cytokines, both of which can inhibit bile acid transport in the liver, resulting in cholestasis [8]. Clinically asymptomatic shunts may be detected by chance. Neonates may also present with cholestasis [9], hypoglycemia and unexplained galactosemia [10]. In countries where babies are always tested for hereditary galactosemia after a few days of milk feeding, the incidence of congenital portosystemic shunts has been estimated at 1 in 30,000 births [9].

Congenital portosystemic shunts are diagnosed with imaging studies such as Doppler ultrasound, computed tomography (CT) scan and magnetic resonance angiography [11]. Early diagnosis of a intrahepatic portosystemic venous shunt is important because the condition can lead to hepatic encephalopathy and other complications such as benign or malignant liver tumors, persistent thrombocytopenia, vascular over-circulation or hepatopulmonary syndrome [6]. These complications should be carefully investigated in a child with a portosystemic shunt, and conversely, a congenital portosystemic shunt should be searched for in children presenting with one of these conditions.

Spontaneous closure of an intrahepatic shunt usually occurs by 1 or 2 years of age [8]. Closure of shunt by radiographic or surgical intervention may be postponed when no complications are detected. In the presence of complications or in the absence of spontaneous closure by 1–2 years of age, closure by radiographic or surgical methods to improve clinical outcome should be considered [12], [13], [14].