Neonatal acute liver failure complicated by patent ductus venosus: Diagnosis and management

Authors


Address reprint requests to Kyle Soltys, M.D., Thomas E. Starzl Transplant Institute, Children's Hospital of Pittsburgh, 3705 Fifth Ave, 7N, Pittsburgh, PA 15213. Telephone: 412-692-6110; FAX: 412-692-6117; E-mail: kyle.soltys@chp.edu

TO THE EDITORS:

Acute liver failure in neonates is rare, is associated with a high mortality rate, and differs from acute liver failure in children and adults with respect to etiologies and outcomes.[1, 2]

CASE REPORT

A 7-day-old male child presented with acute liver failure. On arrival, he was hemodynamically stable with normal renal function and mental status. A physical examination revealed icterus and hepatosplenomegaly. Laboratory results were remarkable for thrombocytopenia and coagulopathy with elevated serum aminotransferase and ammonia levels (Table 1). Abdominal ultrasound (US) showed mild ascites, whereas transcranial US was unremarkable. As part of the diagnostic evaluation, a blood test for Enterovirus was positive with 2500 RNA copies/mL.

Table 1.  
 Total Bilirubin (mg/dL)Direct Bilirubin (mg/dL)Aspartate Aminotransferase (U/L)Alanine Aminotransferase (U/L)Prothrombin TimeInternational Normalized RatioGamma-Glutamyl Transpeptidase (mg/dL)Ammonia (μmol/L)
Before admission12Not available10,5911234Not available1.8Not available124
At admission131.1645587140.54.4127135
Before the procedure40.920.253110292.997226
POD 137.819.55112223.42.269114
POD 1916.89.3160576151.210429
POD 347.3Not available817711.91.1358Not available
POD 1190.80.16168Not available1.0308Not available
POD 2650.40.17163Not availableNot available308Not available

The workup was negative for other causes of acute liver failure. In the absence of a specific therapy for Enterovirus, the child was managed with supportive care. The venous ammonia level steadily increased to a peak of 226 μmol despite lactulose and restricted protein intake. He developed clinical encephalopathy with a peak of stage II. The rise in serum ammonia was accompanied by a continued rise in the total bilirubin level to 40.9 mg/dL with improvements in the aspartate aminotransferase level, international normalized ratio, and albumin level (Table 1). The disparity between the improving international normalized ratio and albumin levels and rising ammonia and bilirubin levels with falling aminotransferase levels prompted repeat US of the liver, which was suspicious for a patent ductus venosus (PDV); this was confirmed with computed tomography (CT) angiography (Fig. 1).

Figure 1.

 

The PDV was presumed to be contributing to the hyperammonemia, and the decision was made to embolize the PDV. After the successful deployment of an Amplatzer 4 vascular plug (St. Jude Medical, St Paul, MN) within the PDV (Fig. 1), the ammonia level fell from 226 to 110 μmol. Repeat liver US on postoperative day (POD) 1 revealed incomplete closure of the ductus venosus (DV) with persistent but significantly diminished flow across the Amplatzer occlusion device. Another US examination on POD 14 showed no demonstrable flow in the DV with a patent hepatic vasculature with normal flow patterns (Fig. 1). By POD 14 (hospital day 25), the ammonia level was 37 μmol/L, and the total bilirubin level was 20.8 mg/dL. The child was discharged with an ammonia level of 29 μmol/L and a total bilirubin level of 16.8 mg/dL (Table 1).

DISCUSSION

The Pediatric Acute Liver Failure Study Group established entry criteria for enrollment in the registry to include patients with no known underlying liver disease with evidence of severe liver-based coagulopathy without encephalopathy.[1, 3] The causes include acute acetaminophen toxicity (14%), metabolic disease (10%), autoimmune liver disease (6%), non-acetaminophen drug-related hepatotoxicity (5%), infections (6%), other conditions (10%), and indeterminate causes (49%). In this case, there was a definite association with an Enterovirus infection, which has been reported previously.[4] However, the failure of the hyperammonemia and hyperbilirubinemia to resolve despite optimal supportive therapy prompted further investigation. It appears that a PDV exacerbated acute liver failure secondary to the Enterovirus infection. The DV is normally open at the time of the birth and naturally closes during the first week of life in most full-term neonates; however, it may take much longer to close in preterm neonates. A PDV has a considerable effect on crucial liver functions such as ammonia detoxification, blood coagulation, and regulation of the serum total bile acid concentration in early neonates.[5] A PDV results in an intrahepatic portosystemic shunt with shunting of the portal blood into the systemic circulation and resultant hyperammonemia and encephalopathy. Similarly, in this case, after the successful occlusion of the PDV, there was a dramatic resolution of the hyperammonemia and hyperbilirubinemia.

In conclusion, a PDV contributing to hyperammonemia and hyperbilirubinemia associated with acute liver failure has never before been described in the literature. With advances in interventional radiological techniques, the closure of a PDV, even in newborns, is now feasible in a minimally invasive fashion. Embolization with an occlusion device in interventional radiology is the preferred method.

  • Rajeev Sharma, M.D.1

  • John Crowley, M.D.2

  • Robert Squires, M.D.3

  • Geoffrey Bond, M.D.4

  • Rakesh Sindhi, M.D.1

  • George Mazariegos, M.D.1

  • Kyle Soltys, M.D.4

  • 1Pediatric Transplantation, 2Radiology3Gastroenterology, and 4Thomas E. StarzlTransplant Institute,

  • Children's Hospital of Pittsburgh

  • Pittsburgh, PA

Abbreviations
CT

computed tomography

DV

ductus venosus

IVC

inferior vena cava

PDV

patent ductus venosus

POD

postoperative day

US

ultrasound

Ancillary