Challenges in pediatric inherited/metabolic liver disease: Focus on the disease spectrum, diagnosis and management of relatively common disorders

Abstract

The clinical scenario of pediatric liver disease is becoming more intricate due to changes in the disease spectrum, in which an increasing number of inherited/ metabolic liver diseases are reported, while infectious diseases show a decreasing trend. The similar clinical manifestations caused by inherited/metabolic diseases might be under-recognized or misdiagnosed due to nonspecific characteristics. A delayed visit to a doctor due to a lack of symptoms or mild symptoms at an early stage will result in late diagnosis and treatment. Moreover, limited diagnostic approaches, especially liver biopsy, are not easily accepted by pediatric patients, leading to challenges in etiological diagnosis. Liver dysfunction due to inherited/metabolic diseases is often caused by a variety of metabolites, so precision treatment is difficult; symptomatic treatment is a compelling option for inherited disorders.

The epidemiological characteristics of liver disease in hospitalized children: a 10-year single-center retrospective study

“…About 20% of pediatric liver transplants are performed for single-gene liver diseases, and almost half of chronic liver diseases that manifest in childhood have a genetic basis ( 27 ). Clinical features that are similar and caused by IMLDs may be under-recognized or misdiagnosed due to their non-specific nature ( 4 ). This study observed that IMLD presents a range of clinical manifestations.…”

“…In our cohort, out of the 1,111 cases with an unknown diagnosis, only 35.3% underwent genetic testing and only 17.1% underwent liver biopsy, owing to limited resources. Furthermore, as 80.1% of the cases occurred during infancy, the restricted diagnostic options available, combined with vague or non-existent symptoms, make it challenging to determine the cause ( 4 ).…”

“…Next-generation sequencing (NGS) has become a powerful diagnostic tool in recent years ( 3 ), particularly with the application of panel-based NGS and whole-exome sequencing (WES). The growing prevalence of gene sequencing in clinical settings has also altered the range of liver diseases ( 4 , 5 ). A growing number of novel genetic diseases have been added to the list of pediatric liver disease etiologies.…”

Insights into the Management of Chronic Hepatitis in Children—From Oxidative Stress to Antioxidant Therapy

“…It has been recently discovered that vitamin D [10] and melatonin [11] have been shown to improve liver function in children with nonalcoholic fatty liver disease (NAFLD). Vitamin D has garnered specific attention as one of the contributing factors of autoimmunity because it acts as an immunomodulator and inhibits inflammation by reducing T and B cell auto-aggression.…”