We appreciate Dr. Hu and Dr. Yang's interest in our recent study [1, 2].

First, we agree with your concern regarding how the new nomenclature of metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD with increased alcohol intake (MetALD) can improve patient management in clinical practice, and there is a need for further investigation [3-5]. Regarding the effect of alcohol consumption affecting the interpretation of the findings, we agree that the effect may vary depending on the metabolic comorbidity of each patient. A recent study investigating the varying levels of alcohol consumption in MASLD and MetALD showed that moderate alcohol intake in MASLD is associated with significant fibrosis and progressive disease [6]. As more evidence accumulates on the relationship between alcohol consumption and clinical outcomes in patients across diverse metabolic environments, it may ultimately guide the development of personalised strategies.

As for the comment regarding intervention strategies for high-risk populations, we would like to highlight that the objective of this study was not to provide specific intervention recommendations but rather to investigate whether cancer risk persists under the new terminology of MASLD and MetALD given that cancer is one of the common causes of mortality in non-alcoholic fatty liver disease (NAFLD) [7]. The study found that MASLD and MetALD were associated with an increased risk of cancer, particularly liver and gastrointestinal cancers. By raising the awareness that those populations are more at risk, we hope to contribute to building a rationale for intervention strategy in the future.

Regarding the question raised about the global applicability of this new nomenclature, we would like to remark that the three large pan-national liver associations including the American Association for the Study of Liver Diseases, the European Association for the Study of the Liver and the Latin American Association for the Study of the Liver have adopted the term to address the exclusionary and stigmatising nature of NAFLD and the limitations of metabolic dysfunction-associated fatty liver disease neglecting alcohol consumption and non-alcoholic steatohepatitis [5]. As our study exclusively included the South Korean population, the findings should be validated across more diverse ethnic groups.

We appreciate the comment regarding unmeasured confounders such as genetic factors, and we agree that there is a need for incorporating genetic factors to provide a more comprehensive assessment. Inherited factors play a major role in the development and progression of MASLD, synergising with the metabolic causes [8]. Studies have suggested that PNPLA3 and TM6SF2 play a role as major risk factors for cirrhosis and hepatocellular carcinoma [8]. Future research incorporating the genetic factors along with metabolic and lifestyle factors would enhance our understanding of the pathogenesis of MASLD and innovate cancer management in patients with MASLD and MetALD.

To better cope with the growing threat of cancer in MASLD and MetALD, having potent and efficient intervention strategies matters. Future research involving a complex interplay of genetic and metabolic factors along with environmental factors in cancer risk will advance our understanding and prevention strategies can be expected to improve.

我们感谢 胡 博士和杨博士对我们最近的研究的兴趣 [1， 2]。

首先，我们同意您的担忧，即代谢功能障碍相关脂肪性肝病 （MASLD） 和 MASLD 伴酒精摄入增加 （MetALD） 的新命名如何改善临床实践中的患者管理，需要进一步研究 [3-5]。关于饮酒影响结果解释的影响，我们同意这种影响可能因每位患者的代谢合并症而异。最近一项调查 MASLD 和 MetALD 不同饮酒水平的研究表明，MASLD 中的适度饮酒与显着纤维化和疾病进展有关 [6]。随着更多关于不同代谢环境中患者饮酒与临床结果之间关系的证据积累，它可能最终指导个性化策略的制定。

至于关于高危人群干预策略的评论，我们想强调的是，鉴于癌症是非酒精性脂肪性肝病 （NAFLD） 的常见死亡原因之一，本研究的目的不是提供具体的干预建议，而是调查在 MASLD 和 MetALD 新术语下癌症风险是否持续存在 [7].研究发现，MASLD 和 MetALD 与癌症风险增加有关，尤其是肝癌和胃肠道癌。通过提高人们对这些人群面临更大风险的认识，我们希望为未来的干预策略建立基础做出贡献。

关于这一新命名法的全球适用性的问题，我们想指出的是，包括美国肝病研究协会、欧洲肝脏研究协会和拉丁美洲肝脏研究协会在内的三个大型泛国家肝脏协会已经采用了该术语来解决 NAFLD 的排斥和污名化性质以及代谢功能障碍相关脂肪肝的局限性忽视饮酒的疾病和非酒精性脂肪性肝炎 [5]。由于我们的研究仅包括韩国人口，因此应该在更多样化的种族群体中验证这些发现。

我们感谢关于遗传因素等未测量混杂因素的评论，并且我们同意有必要纳入遗传因素以提供更全面的评估。遗传因素在 MASLD 的发生和进展中起主要作用，与代谢原因协同作用 [8]。研究表明，PNPLA3 和 TM6SF2 是肝硬化和肝细胞癌的主要危险因素 [8]。将遗传因素与代谢和生活方式因素相结合的未来研究将增强我们对 MASLD 发病机制的理解，并创新 MASLD 和 MetALD 患者的癌症管理。

为了更好地应对 MASLD 和 MetALD 中日益增长的癌症威胁，制定有效和高效的干预策略很重要。未来的研究涉及遗传和代谢因素以及癌症风险中的环境因素的复杂相互作用，将促进我们的理解，并且有望改进预防策略。