Gestational alloimmune liver disease reconsidered: Advocating for a new nomenclature and enhanced diagnosis accuracy

Abstract

Gestational alloimmune liver disease (GALD), previously known as neonatal hemochromatosis, is a rare antenatal immune condition in which maternal antibodies target the fetal liver, leading to a spectrum of liver injury. Although GALD in the leading cause of neonatal liver failure, recent evidence highlights its association with milder phenotypes. A maternal history of miscarriages or stillbirths may be present. GALD is characterized by hepatic and extrahepatic iron overload sparing the reticuloendothelial system. The transferrin saturation coefficient is the most reliable marker of iron overload, and salivary gland biopsy may assist in diagnosis. Early recognition is crucial, as GALD is treatable. Management involves both acute neonatal treatment and preventive strategies for future pregnancies. Recurrence may reach 90% but can be effectively prevented with antenatal intravenous immunoglobulin therapy. We report four cases of GALD managed in gastroenterology unit of the Sainte-Justine center in Montreal, Canada. A literature review was also conducted to explore the etiopathogenesis, diagnosis, treatment options, and outcomes of the GALD. A total of 39 studies published between 2008 and 2024 were identified through PubMed, Google Scholar, and EMBASE using the terms "gestational alloimmune liver disease" and "neonatal hemochromatosis".

Keywords: Gestational allo-immune liver disease; Intravenous immunoglobulin therapy; Liver transplantation; Neonatal hemochromatosis; Neonatal liver failure.

Figure 1

T2 signal loss in liver (case 4).