Abstract
Gestational alloimmune liver disease (GALD) is a leading cause of neonatal acute liver failure (ALF) with unique histologic features but no established histologic scoring criteria. This study aimed to develop an accurate histologic scoring system to distinguish GALD from non-GALD neonatal ALF. A preliminary system using 6 histologic features characteristic of GALD was created. Four pathologists from 2 institutions applied this system to GALD (n=11) and non-GALD (n=20) neonatal ALF cases from 2008 to 2020. Four cases of Trisomy 21-associated transient myeloproliferative disorder were analyzed separately, as these patients can present with neonatal ALF and display GALD histologic features but are clinically distinguishable. Area under the receiver operating curve (AUROC) was fitted for stepwise combinations of features to determine the most accurate scoring system. GALD histologic features included extensive parenchymal fibrosis and neotubules, and a paucity of healthy hepatocytes, portal tract involvement, extramedullary hematopoiesis, and inflammation. A revised 3-feature system including parenchymal fibrosis, neotubules, and hepatocyte characterization established highest accuracy with an AUROC of 0.891 ( P <0.001). Importantly, there were no significant interinstitutional differences in scores assigned to GALD versus non-GALD cases. A 3-factor score of <2 had 100% sensitivity (95% CI: 74%-100%) to exclude GALD and a score >5 had 95% specificity (95% CI: 76%-100%) to diagnose GALD. This study establishes a highly accurate histologic scoring system to differentiate GALD from non-GALD neonatal ALF. Findings may aid in accurate diagnosis of index cases, reducing recurrence risk in subsequent pregnancies and lowering morbidity and mortality associated with GALD.