Introduction: Recurrent acute liver failure (RALF) in children is defined as two or more episodes of acute liver failure with complete recovery in between. Several genetic mutations have been found to be associated with this condition, including NBAS, RINT1, and SCYL1.

Methods: To describe the prognosis and disease course of this rare condition we conducted a review using PubMed for English-language studies of RALF occurring in children with NBAS, RINT1 or SCYL1 mutations.

Results: A total of 109 (52 males, 47.7%) patients were identified, with first presentation at a median age of 10 months and preceded by fever in in 106 (97.2%) children. Patients had a median of 4 (range 1- 30) RALF episodes with only 6 (5%) patients experiencing events after age 10 years. Commonest mutated genes identified were NBAS (80%, n=88) and SCYL1 (14%, n=15). Liver transplant was undertaken in 12 (11%) patients, including 9 (75%) performed during a RALF episode, with no recurrences reported post-transplant.  Death was reported in 9 (8.2%) patients (8.2%) died, 8 of them with their native liver.

Conclusion: Most patients with RALF present in the first year of life and have a self-limiting course.  Although RALF is rare, it should be considered in any patient presenting with severe acute liver injury associated with fevers. Parents should be instructed to treat fever aggressively and seek medical advice. Genetic investigation should be obtained with whole exome sequencing, but a designated genetic panel is needed. Management is largely supportive ideally in an experienced LT center, as liver transplantation might be indicated in selected cases.