Integrating Machine Learning and Follow-Up Variables to Improve Early Detection of Hepatocellular Carcinoma in Tyrosinemia Type 1: A Multicenter Study.
Journal:
International journal of molecular sciences
PMID:
40332516
Abstract
Hepatocellular carcinoma (HCC) is a major complication of tyrosinemia type 1 (HT-1), an inborn error of metabolism affecting tyrosine catabolism. The risk of HCC is higher in late diagnoses despite treatment. Alpha-fetoprotein (AFP) is widely used to detect liver cancer but has limitations in early-stage HCC detection. This study aimed to implement a machine-learning (ML) approach to identify the most relevant laboratory variables to predict AFP alteration using constrained multidimensional data from Chilean and Italian HT-1 cohorts. A longitudinal retrospective study analyzed 219 records from 35 HT-1 patients, including 8 with HCC and 5 diagnosed through newborn screening. The dataset contained biochemical and demographic variables that were analyzed using the eXtreme Gradient Boosting algorithm, which was trained to predict abnormal AFP levels (>5 ng/mL). Four key variables emerged as significant predictors: alanine transaminase (ALT), alkaline phosphatase, age at diagnosis, and current age. ALT emerged as the most promising indicator of AFP alteration, potentially preceding AFP level changes and improving HCC detection specificity at a cut-off value of 29 UI/L (AUROC = 0.73). Despite limited data from this rare disease, the ML approach successfully analyzed follow-up biomarkers, identifying ALT as an early predictor of AFP elevation and a potential biomarker for HCC progression.
Authors
Keywords
Adolescent
Adult
Alanine Transaminase
Alkaline Phosphatase
alpha-Fetoproteins
Biomarkers, Tumor
Carcinoma, Hepatocellular
Child
Child, Preschool
Early Detection of Cancer
Female
Follow-Up Studies
Humans
Infant
Infant, Newborn
Liver Neoplasms
Longitudinal Studies
Machine Learning
Male
Middle Aged
Retrospective Studies
Tyrosinemias
Young Adult