Hemophagocytic lymphohistiocytosis: pediatric hepatic perspective

Abstract

BackgroundHepatic manifestations of hemophagocytic lymphohistiocytosis (HLH), an underrecognized primary presentation in pediatric age group, mandate high levels of suspicion for early diagnosis.AimThis is to study the frequencies of clinical and laboratory hepatic involvement in patients with familial/primary or secondary/acquired HLH in relation to disease reactivation and outcome.MethodsA 6-month retrospective cohort study recruited 35 patients with HLH. Detailed clinical, laboratory, and genetic characteristics of HLH were collected. Hepatic transaminases and synthetic liver functions were collected at presentation, weeks 2 and 8 after starting treatment, and at time of reactivation. Biochemical liver involvement was considered when alanine aminotransferase (ALT) lived three-times more than the upper normal level. Overall (OS) and reactivation free survival were analyzed according to liver involvement.ResultsTwenty patients (57%) had genetically confirmed HLH, 12 (34.3%) had MUNC13D mutations, 3 (8.5%) had STXBP2 mutations, and 5 (14.3%) had RAB27A mutations, while 9 (25.7%) had no genetic mutations with 4 of them had secondary HLH. Six patients (17.2%) patients had unknown genetics status. Median (IQR) age of the whole group was 18 months (6–36) with an age range of 2–108 months. Liver enlargement was detected at diagnosis in 29 (82.9%) and at reactivation in 18 (51.4%) patients. Eight (22.86%) patients had biochemical hepatic involvement at presentation with no significant difference in their demographic, initial clinical presentation, survival, or the type of mutant gene according to liver involvement.ConclusionVariable hepatic biochemical involvement might be the presenting manifestation of HLH at diagnosis and upon reactivation, yet it did not impact disease outcome.