Recurrent Acute Liver Failure in Children: A Systematic Review of Genetic Etiologies, Diagnostic Clues, and Liver Transplantation

Why clinicians should know about it

• Picked for Genetics (clinical) (top studies of the week, 1 November 2026): Systematic review addresses genetic diagnoses and testing in recurrent pediatric

Abstract

BACKGROUND: Recurrent acute liver failure (RALF) is a rare phenotype with heterogeneous inherited causes. METHODS: We conducted a PRISMA 2020 systematic review of PubMed/MEDLINE and Web of Science Core Collection. Reports were classified into two non-combinable evidence sets: strict RALF, requiring at least two documented pediatric acute liver failure episodes with recovery of liver synthetic function between episodes, and contextual disease-specific evidence used only to inform broader natural history, treatment, or transplantation. RESULTS: The searches identified 128 records; 30 duplicates were removed, and 98 records were screened. Forty-eight full texts were assessed, and 44 publications representing 41 study or cohort units were retained across both evidence sets. The evidence consisted predominantly of case reports, small case series, and retrospective cohorts, with inconsistent RALF definitions and incompletely reported follow-up. The five-group framework is a pragmatic organization of reported qualifying disorders rather than an exhaustive genetic classification. CONCLUSIONS: Genomic testing during a first unexplained severe episode is proposed to avoid waiting for recurrence, but most disorder-specific treatment and transplantation conclusions remain based on limited observational evidence and expert practice.

Abstract as published, via PubMed.