Response to Letter to the Editor Regarding ‘Increasing Prevalence of Steatotic Liver Disease in a Japanese Population’

We sincerely appreciate the authors' thoughtful comments on our study examining long-term trends in steatotic liver disease in Japan [1, 2]. We carefully reviewed each point raised and provide our responses below. We fully acknowledge the limited sensitivity of B-mode ultrasonography for mild steatosis. However, several points indicate that this does not meaningfully affect the robustness of our trends. In Japan, ultrasonography devices cannot be frequently replaced due to clinical and institutional constraints, making it unlikely that device updates explain the rising prevalence. Over the two decades of our study, diagnostic criteria, imaging protocols and image-review processes remained consistent, with examinations by experienced sonographers and confirmation by board-certified hepatologists. This uniformity minimises temporal variability in diagnostic sensitivity. Reduced sensitivity for mild steatosis is also a limitation of all population-based studies using ultrasonography. Given our large sample size and consistent methodology, the steady and significant increases cannot be attributed to device-related detection bias. The authors also highlight potential misclassification due to underreporting of alcohol consumption. Self-reported intake is indeed a universal limitation in epidemiology, and we acknowledged this in the discussion. However, the rising trend of alcohol-associated liver disease in lean individuals supports the validity of our findings. Any underreporting would likely attenuate, not create, upward trends; thus, our results remain robust. We agree that objective biomarkers such as phosphatidylethanol would strengthen future population-based studies, but their use in large-scale health-checkup settings is ethically and practically difficult unless conducted prospectively. Importantly, the absence of such biomarkers does not undermine the long-term trends identified from standardised, routinely collected health-checkup data. Finally, we strongly agree with the authors on the clinical relevance of the lean population. Excessive alcohol intake with insufficient calories leads to malnutrition and sarcopenia, worsening hepatic and overall prognosis. In our study, lean individuals with alcohol-associated liver disease had the highest fibrosis-4 index, indicating increased fibrosis risk. These patients likely have caloric intake displaced by alcohol, resulting in malnutrition, muscle loss and reduced liver reserves [3, 4]. We therefore support the recommendation to incorporate routine nutritional and body composition assessments for individuals with steatosis and a lean phenotype. In summary, while we appreciate the important methodological considerations raised, none of them alter the central message of our study. The prevalence of steatotic liver disease is silently but steadily increasing in Japan. The authors' comments ultimately highlight the significance of our findings. The study was conceptualised and designed by Takao Miwa. Data was collected by Yuki Nakahata and Akihiro Obora. Statistical analyses were performed by Yuki Nakahata. The first draft of the manuscript was written by Yuki Nakahata, Takao Miwa and Masahito Shimizu and the other authors provided critical revisions. All authors reviewed and approved the final version of the manuscript. We respectfully acknowledge the late Dr. Tatsunori Hanai, who made a pivotal contribution to the design and conduct of this study. His insight, mentorship and dedication had a lasting impact on our work, and we remember him with deep gratitude and respect. This study was supported by a Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JP24K18908). The study protocol was reviewed and approved by the Ethical Review Committee of Asahi University Hospital (approval no. 2022-04-02). Informed consent was obtained from all study participants using the opt-out method. The authors declare no conflicts of interest. This article is linked to https://doi.org/10.1111/liv.70476. The data and codes used in this study are available from the corresponding author upon reasonable request. However, additional approval from the Ethical Review Committee of Asahi University Hospital is required to share the data, in accordance with Japanese ethical guidelines.