Severe Acute Hepatitis of Unknown Etiology in Pediatric Patients: Multidisciplinary Clinical Approach

Abstract

Introduction: In mid-2022, the World Health Organization (WHO) declared a moderate-risk outbreak due to an increase in severe acute hepatitis cases of unknown etiology in children. Several reports suggested a viral infection link, with the outbreak spanning over 35 countries. By June 2022, Mexico reported 69 probable cases across 5 entities to the WHO. Case Presentation: A 4-year-old boy presented with vomiting, jaundice, choluria, and hepatomegaly. A multidisciplinary approach was employed, using an algorithm developed exclusively for clinical, epidemiological, and biochemical follow-up. Despite the negative identification of any associated microorganism and the absence of antibodies, liver function tests remained elevated. A fine needle liver biopsy was performed for diagnostic support, followed by histopathological study and sequencing and analysis of the complete high-depth transcriptome. Transcriptome analysis identified dysbiosis-related intestinal microbiota, including increased enterogenic and opportunistic pathogenic bacteria of the genus Clostridium, as well as HERV-K113, implicated in autoimmune disease development. Conclusions: The study's findings suggest possible immune-mediated mechanisms involving dysbiosis of the gut microbiota and the potential role of HERV-K113. Management and control of acute liver disease depend on specific causes, with the main challenge being early determination and implementation of optimal management strategies. The exact pathological mechanisms underlying pediatric acute hepatitis of unknown etiology remain elusive, warranting further studies to confirm or refute these hypotheses and elucidate the underlying pathological mechanisms