Low Alanine Aminotransferase Cut-Off for Predicting Liver Outcomes; A Nationwide Population-Based Longitudinal Cohort Study

Abstract

Background: Recent practice guideline suggests healthy normal alanine aminotransferase (ALT) levels should be less than 30 U/L for males and 19 U/L for females. We tried to validate the prediction power of the 'low cut off' for liver related outcomes in general population. Methods: A total of 426,013 subjects were followed up for 10 years using the National Health Screening Cohort database. Prediction ability of long term mortality and liver related outcomes between conventional (<40 U/L in men and women) and low (<30 U/L in men and <19 U/L in women) ALT cut-off values were compared. Both conventional and low ALT cut-offs predicted liver related unfavorable outcomes in Kaplan-Meier analysis. Findings: Following adjustment for age, body mass index, smoking, exercise, alcohol consumption, fasting blood glucose and cholesterol via multivariate Cox regression, abnormal ALT using new 'low ALT cut off' was significant independent predictors for liver-related mortality, HCC, and decompensated liver events. When the low cut-off criteria were added to the prediction model, the ability to predetect liver-related hard outcomes significantly increased in both men and women (P-values <0.0001). The C-index values for predicting liver-related adverse events were the same in both ALT cut-offs, after adjusting confounding factors (C index value: 0.73~0.88). Interpretation: New low ALT cut-off showed good prediction power for liver related unfavorable outcomes. Funding: This work was supported by grants from the National Research Foundation of Korea (NRF), funded by the Korean Government (2017M3A9C8028794). Declaration of Interest: Nothing to disclose. Ethical Approval: The study was approved by the Hanyang University IRB (HYI-17-073-1) and the NIHS IRB. Informed consent was waived because of the retrospective nature of the study. All process was performed in accordance with the relevant guidelines and regulations by both IRB and HIRA. We used open data source, so the informed consent waived.