Alanine aminotransferase (ALT) is a crucial enzyme in diagnosing acute and chronic liver disease, reflecting liver health and function.^{1, 2} The upper limit of normal (ULN) for ALT levels is commonly applied uniformly across populations, disregarding variations due to metabolic health, gender and body mass index (BMI). To date, there is no universally accepted ULN value, although current US guidelines suggest the use of standardised cut-offs in men (29–35 U/L) and women (19–25 U/L).^3-5 In this context, Tan et al⁶ report the results of a comprehensive pooled analysis of 349,367 healthy individuals without known liver or metabolic diseases and 134,810 healthy individuals with known metabolic diseases but no known liver diseases to derive updated ULN cut-offs for serum ALT. By incorporating factors such as metabolic health status, gender and body mass index (BMI), the authors aimed to refine diagnostic accuracy and improve patient outcomes in liver disease management. Application of a one-size-fits-all approach bears important limitations due to differences in ALT laboratory assay methodology, which may affect the applicability and accuracy of liver health assessment across diverse populations, and may lead to both missed/delayed diagnosis or overdiagnosis of liver disease.⁷ Recognising these challenges is crucial for advancing liver disease diagnostics and ensuring that patients receive timely and appropriate care tailored to their individual health profiles.

In this study,⁶ the authors conducted an extensive meta-analysis incorporating data from over 423,355 individuals and with consideration of metabolic health status, gender and BMI, derived a contemporary estimate of ALT ULN 32 U/L for individuals without known metabolic or liver diseases (36 U/L in males, 28 U/L in females). Among individuals with metabolic disease but no known liver disease, the authors determined an ALT ULN 40 U/L among overweight/obese individuals (29 U/L if normal weight) and 36 U/L among individuals with diabetes mellitus type 2 (33 U/L if no diabetes mellitus type 2). This nuanced approach to determining ALT ULN offers a potentially more accurate diagnostic threshold to enhance liver health assessment for clinical practice and public/population health and underscores the need for further research on ALT cut-off standards across diverse populations, stronger US and global harmonisation of ALT analyzer and assay measurements and updated clinical guidelines which incorporate ALT intervals which reflect individual metabolic variation. The study cohort in this meta-analysis was predominantly derived from Asian populations, and with significant heterogeneity across studies, and therefore caution is needed in universal application of these standards to non-Asian populations. Due to significant variability in chemical analyzers used in laboratories, harmonising ALT measurements across populations may require standardisation of international units for serum ALT levels in accordance with global standards such as those from the International Federation of Clinical Chemistry and Laboratory Medicine.^{8, 9} Acknowledging these limitations is essential for refining ALT ULNs, enhancing diagnostic accuracy and ensuring the findings' applicability in diverse clinical settings. This important cohort study analysis represents an early but significant step towards personalised liver diagnostics and should prompt broader support and investment by key medical, laboratory and public health stakeholders to facilitate additional research to provide more refined, evidence-based tools for the assessment of liver disease.

丙氨酸氨基转移酶（ALT）是诊断急慢性肝病的关键酶，反映肝脏的健康和功能。^{1, 2} ALT 水平的正常上限 (ULN) 通常在不同人群中统一适用，不考虑代谢健康、性别和体重指数 (BMI) 造成的差异。迄今为止，还没有普遍接受的 ULN 值，尽管美国现行指南建议对男性 (29–35 U/L) 和女性 (19–25 U/L) 使用标准化临界值。^3-5在此背景下，Tan 等人⁶报告了对 349,367 名没有已知肝脏或代谢疾病的健康个体以及 134,810 名患有已知代谢疾病但没有已知肝脏疾病的健康个体进行综合汇总分析的结果，以得出更新的 ULN 截止值血清丙氨酸转氨酶。通过综合代谢健康状况、性别和体重指数 (BMI) 等因素，作者旨在提高诊断准确性并改善肝病管理中的患者预后。由于 ALT 实验室检测方法的差异，一刀切的方法的应用具有重要的局限性，这可能会影响不同人群肝脏健康评估的适用性和准确性，并可能导致漏诊/延迟诊断或过度诊断。肝病。⁷认识到这些挑战对于推进肝病诊断并确保患者获得根据其个人健康状况量身定制的及时、适当的护理至关重要。

在这项研究中，⁶作者进行了广泛的荟萃分析，纳入了超过 423,355 名个体的数据，并考虑了代谢健康状况、性别和 BMI，得出了无已知代谢或肝脏疾病的个体 ALT ULN 32 U/L 的当代估计值（男性 36 U/L，女性 28 U/L）。在患有代谢疾病但无已知肝脏疾病的个体中，作者确定超重/肥胖个体的 ALT ULN 为 40 U/L（如果体重正常则为 29 U/L），2 型糖尿病患者的 ALT ULN 为 36 U/L（33 U/L）。 /L（如果没有 2 型糖尿病）。这种确定 ALT ULN 的细致入微的方法提供了一个可能更准确的诊断阈值，以增强临床实践和公众/人群健康的肝脏健康评估，并强调需要对不同人群的 ALT 临界标准进行进一步研究，加强美国和全球统一ALT 分析仪和测定测量以及更新的临床指南，其中纳入了反映个体代谢变化的 ALT 间隔。本荟萃分析中的研究队列主要来自亚洲人群，并且各研究之间存在显着异质性，因此在将这些标准普遍应用于非亚洲人群时需要谨慎。由于实验室使用的化学分析仪存在显着差异，协调不同人群的 ALT 测量可能需要根据全球标准（例如国际临床化学和实验医学联合会的标准）对血清 ALT 水平的国际单位进行标准化。^{8, 9}承认这些局限性对于完善 ALT ULN、提高诊断准确性并确保研究结果在不同临床环境中的适用性至关重要。这项重要的队列研究分析代表了个性化肝脏诊断的早期但重要的一步，并应促使主要医疗、实验室和公共卫生利益相关者提供更广泛的支持和投资，以促进更多研究，为肝病评估提供更精细、循证的工具。 。