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Continuous age- and sex-specific reference ranges of liver enzymes in Chinese children and application in pediatric non-alcoholic fatty liver disease

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Abstract

Background

Alanine aminotransferase (ALT) is widely used to screen patients with hepatic diseases. However, the current reference ranges (< 50 U/L) were developed by laboratories and have not been validated in populations with a large number of healthy individuals.

Methods

This study collected venous blood and anthropometric data from a total of 13,287 healthy children aged 3 months to 18 years who underwent routine physical examinations in the Department of Pediatric Healthcare. We applied the least mean square algorithm to establish age- and sex-related reference percentiles of serum levels of transaminases. For validation, we recruited 4276 children and adolescents with obesity/overweight who underwent evaluation and metabolic tests in the hospital. Using receiver operating characteristic curves, we determined age- and sex-specific upper limit percentiles of liver enzymes for fatty liver diseases.

Results

This study revealed a significant correlation between serum transaminase levels and age and sex (P < 0.01). These transaminase levels exhibited age- and sex-specific patterns. Among individuals in the non-alcoholic fatty liver disease (NAFLD) cohort, elevated ALT levels displayed a positive association with clinical markers of disease severity, including homeostatic model assessment of insulin resistance, waist–hip ratio, and serum uric acid levels (P < 0.01). According to the receiver operating characteristic curves, ALT levels at the 92.58th percentile for boys and the 92.07th percentile for girls yielded the highest accuracy and specificity.

Conclusions

This study provides age- and sex-specific reference ranges for ALT, aspartate aminotransferase, and γ-glutamyltransferase in Chinese children and adolescents, making it the largest population study to date. Furthermore, the study establishes a precise upper limit for ALT levels, facilitating their use in NAFLD screening.

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Data availability

The data sets generated and analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

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Funding

This study was supported by grants from the National Key Research and Development Program of China (Nos. 2021YFC2701901 and 2016YFC1305301), National Natural Science Foundation of China (Nos. 82370863 and 81570759), and Zhejiang Provincial Key Disciplines of Medicine (Innovation Discipline, 11-CX24).

Author information

Authors and Affiliations

  1. Department of Endocrinology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou, 310051, China

    Zhao-Yuan Wu, Si-Wei Chi, Liu-Jian Ouyang, Xiao-Qin Xu, Jing-Nan Chen, Bing-Han Jin, Rahim Ullah, Xue-Lian Zhou, Ke Huang, Guan-Ping Dong, Yan Ni, Jun-Fen Fu & Wei Wu

  2. Department of Data and Information, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Zhe-Ming Li

  3. Department of Child Health Care, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China

    Ying Shen & Jie Shao

  4. Department of Thoracic & Cardiovascular Surgery, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, 3333 Binsheng Road, Hangzhou, 310051, China

    Qiang Shu

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  1. Zhao-Yuan Wu
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Contributions

WZY contributed to investigation, conceptualization, resources, data curation, methodology, formal analysis, validation, writing of the original draft, reviewing and editing. CSW and OLJ contributed to investigation, conceptualization, methodology, formal analysis, validation, writing of the original draft, reviewing and editing. XXQ, NY and SQ contributed to investigation, conceptualization, resources, and data curation. CJN and JBH contributed to writing of the original draft, reviewing and editing. UR contributed to investigation, conceptualization, writing of the original draft, reviewing and editing. ZXL, HK, WW, DGP, LZM, SY, SJ contributed to resources and data curation. FJF and WW contributed to investigation and conceptualization, and was responsible for funding acquisition and supervision. All authors critically reviewed and approved the final version of the manuscript.

Corresponding authors

Correspondence to Jun-Fen Fu, Qiang Shu or Wei Wu.

Ethics declarations

Ethical approval

This study was approved by the Ethics Committee of Zhejiang University (2021-IRB-301). Informed consent to participate in the study has been obtained from participants (or their parent or legal guardian in the case of children under 16).

Conflict of interest

No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article. Authors Jun-Fen Fu and Qiang Shu are member of the Editorial Board and Chief Editor for World Journal of Pediatrics, respectively. This paper was handled by the other Editor and has undergone rigorous peer-review process. Authors Jun-Fen Fu and Qiang Shu were not involved in the journal’s review of, or decisions related to, this manuscript. The authors have no conflict of interest to declare.

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Wu, ZY., Chi, SW., Ouyang, LJ. et al. Continuous age- and sex-specific reference ranges of liver enzymes in Chinese children and application in pediatric non-alcoholic fatty liver disease. World J Pediatr (2024). https://doi.org/10.1007/s12519-023-00789-5

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