1.
We thank Dai and Wang for their thoughtful comments [1] on our study [2], and we agree with their central point. Our findings carry two messages. First, aminotransferases show reproducible seasonal variation, so clinical decisions near metabolic dysfunction‐associated steatotic liver disease (MASLD) screening thresholds may be influenced by the season of measurement. Second, greater seasonal amplitude was associated with poorer long‐term glycemic control, so even a winter‐only threshold crossing warrants attention. We fully endorse their proposed season‐aware confirmation, namely repeat testing in a comparable seasonal context and integration with fibrosis‐oriented and cardiometabolic risk assessment. We also suggest considering measurement in at least two seasons, preferably summer and winter, rather than judging from a single seasonal value.
At the same time, the discordance we reported reflects measurement timing in patients near the cutoff, and we agree with their caution that it should not be read as seasonal onset or remission of MASLD or as a direct reclassification of risk. Current MASLD guidance prioritizes fibrosis evaluation in people with Type 2 diabetes mellitus (T2DM) [3], and the AASLD practice guidance notes that persistent or intermittent elevations can suggest chronic liver injury [4]. Given our findings, winter threshold crossing in a borderline patient is best treated as a signal for confirmation and fibrosis‐oriented assessment, and a summer value just below the threshold as an indication for retesting in a subsequent season.
Their concept of winter as a natural metabolic stress test is attractive. Crossing the threshold only in winter may reflect not random variation alone but a diminished capacity to maintain systemic metabolic homeostasis under shorter photoperiods and colder temperatures. The asymmetry between aspartate aminotransferase (AST) and alanine aminotransferase (ALT) is compatible with this interpretation. The association between AST amplitude and final glycated haemoglobin (HbA1c) persisted when baseline AST was replaced by the mean enzyme level over follow‐up and in a split‐period analysis, whereas the ALT association was attenuated in both [2]. As with visit‐to‐visit variability in other cardiometabolic risk factors, which has been associated with adverse outcomes [5], amplitude may mark metabolic resilience rather than liver injury alone.
As they note, the practical implication is not seasonal threshold adjustment. Rather, borderline values should be interpreted against the individual seasonal pattern. Future studies should include populations without T2DM and examine whether fibrosis markers show similar seasonality and whether season‐aware pathways improve MASLD case‐finding, ideally in cohorts with imaging or histologic data.
Author Contributions
Ryota Toki drafted the letter. Masaya Sakamoto critically revised the letter. Both authors approved the final version and agree to be accountable for all aspects of the work.
Funding
The authors have nothing to report.
Conflicts of Interest
The authors declare no conflicts of interest.
Linked Article
This letter responds to Dai and Wang (https://doi.org/10.1111/liv.70807) and refers to Toki et al. (https://doi.org/10.1111/liv.70743).
Acknowledgements
During the preparation of this letter, the authors used Claude (Anthropic) for English language editing. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.
Data Availability Statement
The authors have nothing to report.
References
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Associated Data
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Data Availability Statement
The authors have nothing to report.