Neonatal Acute Liver Failure in a Preterm Neonate with Gestational Alloimmune Liver Disease and Congenital Portosystemic Shunts

Introduction: Gestational alloimmune liver disease (GALD) is a leading cause of neonatal acute liver failure (NALF), a rare but important diagnosis. Congenital portosystemic shunts (CPSs) are rare vascular anomalies that leave patients at risk for developing a wide spectrum of complications and have not been previously associated with GALD. In this case, we present a newborn male with NALF secondary to GALD complicated by intrahepatic shunts.

Case Description: The patient is a 30 weeks gestational age male born to a 28-year-old gravida 2 para 0 mother via urgent cesarean section for severe placental malperfusion. The pregnancy was complicated by severe intrauterine growth restriction, oligohydramnios, and maternal COVID-19 infection. The patient’s initial NICU course was remarkable for respiratory distress requiring ventilatory support, hypotension requiring inotropes and stress dose steroids, and coagulopathy with bleeding requiring transfusion of multiple blood products. An abdominal ultrasound showed large congenital intrahepatic portosystemic shunts. Over the course of the hospitalization, the infant progressed to fulminant hepatic failure with associated coagulopathy, hypoalbuminemia, direct hyperbilirubinemia, and hyperammonemia. There was persistent anasarca in addition to elevated ferritin (1,922 ng/dL) and alpha-fetoprotein (97,855 ng/mL). Serial SARS-CoV-2 NAAT were negative. In consultation with the hepatologist there was high clinical suspicion for GALD, and treatment with intravenous immunoglobulin was initiated, however, no clinical or laboratory improvement was noted. Abdominal MRI showed progression of the large CPSs and enlargement of the hepatic arteries. The infant continued to deteriorate, was transitioned to comfort care, and died on day of life 82. A limited autopsy revealed a markedly edematous and jaundiced male with grossly enlarged liver with hepatocellular cholestasis, portal fibrosis, diffuse hepatobiliary iron depositions, and C5b9 positivity within hepatocytes confirming a diagnosis of GALD.

Discussion: Neonatal hemochromatosis is the phenotypic result of severe liver injury leading to iron overload and extrahepatic siderosis, the mechanism of hepatic injury now recognized in GALD. Liver failure in newborns with GALD often presents with marked coagulopathy, hypoalbuminemia, and edema with and without ascites. The establishment of the diagnosis is crucial given without treatment, the prognosis is very poor. There have been no case reports of neonates with acute liver failure from CPSs or CPSs occurring with GALD. We hypothesize that the presence of CPSs worsens the clinical course of GALD through an unknown mechanism that further expedites hepatocellular damage. Furthermore, the role of SARS-CoV-2 infection and transmission in the neonatal population is still unknown.

Conclusion: Neonatal acute liver failure caused by GALD is a rare but potentially fatal diagnosis. CPSs associated with GALD have not been previously documented. This case demonstrates the interplay of these disease entities likely contributing towards a more severe course of NALF and highlights the importance of early identification for guiding management.