Клинико-генетическая характеристика детей с подозрением на наследственные заболевания печени. Алгоритм дифференциальной диагностики

Abstract

Hepatitides of unspecified etiology in children may be caused by genetic disorders. Its early detection can improve the patient management with understanding the pathogenesis, more accurately predicting the course, preventive examinations and prescribing specialized pathogenetic therapy in selected cases. However, currently there are no guidelines for the optimal diagnosis of such cases. The purpose of this research was to develop an algorithm for the differential diagnosis of hepatitides of unspecified etiology in children based on the identified clinical and genetic features of hereditary liver diseases. Materials and methods used: a single-center cohort retrospective study of 179 children with hepatitides of unspecified etiology aged 0 to 18 y/o was conducted. All patients had undergone genetic examination, based on the results of which the two groups were formed as follows: with and without genetic liver disease. Statistical analysis of the patients’ clinical, laboratory and instrumental examinations was aimed at identifying key markers for common hereditary liver diseases in different age groups as well as statistically significant differences in rare genetic reasons for hepatitis. Results: 27 different genetic liver diseases were identified in 101 (56.4%) with hepatitis of unspecified etiology. The most frequently detected diseases were Wilson's disease (41 or 40.6%), alpha-1 antitrypsin deficiency (A1AD or AATD) (9 or 8.9%) and Alagille syndrome (ALGS) (8 or 7.9%). Other hereditary pathologies occurred in isolated cases though its total incidence was nearly half of all cases (43 or 42.6%). In order to identify such cases, it is advisable to perform exome sequencing. In order to determine the indications for genetic examination, Authors have developed the mathematical model for assessing the risk of hereditary liver disease (ROC-AUC 0.787 with 95% CI: 0.696-0.877, sensitivity 69.8% with 95% CI: 57.7%-81.3%, specificity 79.2% with 95% CI: 72.3%-84.8%). Conclusion: Authors offer the suggested algorithm for differential diagnosis of hepatitides of unspecified etiology in children that includes, on the first place, the exclusion of the most common genetic liver diseases followed by exome sequencing in high-risk cases that in its turn is calculated using the developed mathematical model.