Xiong ZK, Jiang YZ, Lin YH, Cao JD, Deng TY, Zheng YY. Is metabolic dysfunction-associated steatotic liver disease truly irrelevant? Unmasking the heterogeneity and confounders in pancreatic cancer outcomes. World J Gastroenterol 2026; 32(27): 119356 [DOI: 10.3748/wjg.119356]
Corresponding Author of This Article
Yi-Yuan Zheng, PhD, Laboratory Center, Department of Hepatopathy, Shanghai Municipal Hospital of Traditional Chinese Medicine, No. 274 Zhijiang Middle Road, Shanghai 200071, China. iceroser@126.com
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Gastroenterology & Hepatology
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review-article
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Xiong ZK, Jiang YZ, Lin YH, Cao JD, Deng TY, Zheng YY. Is metabolic dysfunction-associated steatotic liver disease truly irrelevant? Unmasking the heterogeneity and confounders in pancreatic cancer outcomes. World J Gastroenterol 2026; 32(27): 119356 [DOI: 10.3748/wjg.119356]
World J Gastroenterol. Jul 21, 2026; 32(27): 119356 Published online Jul 21, 2026. doi: 10.3748/wjg.119356
Is metabolic dysfunction-associated steatotic liver disease truly irrelevant? Unmasking the heterogeneity and confounders in pancreatic cancer outcomes
Zhe-Kun Xiong, Yan-Hua Lin, Jian-Dong Cao, Tao-Ying Deng, Department of Spleen, Stomach and Hepatobiliary, Zhongshan Hospital of Traditional Chinese Medicine, Zhongshan 528401, Guangdong Province, China
Yu-Zi Jiang, Yi-Yuan Zheng, Laboratory Center, Department of Hepatopathy, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai 200071, China
Co-first authors: Zhe-Kun Xiong and Yu-Zi Jiang.
Author contributions: Zheng YY conceived this work; Xiong ZK and Jiang YZ contributed equally as co-first authors; Xiong ZK, Jiang YZ, Lin YH, Cao JD, and Deng TY researched the literature and wrote the manuscript; all authors thoroughly reviewed and endorsed the final manuscript.
AI contribution statement: AI tools were used solely for language editing and translation support. ChatGPT assisted in improving the clarity and grammar of the English text. The scientific content, data analysis, interpretation, and conclusions were developed entirely by the authors. The authors reviewed and approved all AI-assisted modifications and assume full responsibility for the final manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Yi-Yuan Zheng, PhD, Laboratory Center, Department of Hepatopathy, Shanghai Municipal Hospital of Traditional Chinese Medicine, No. 274 Zhijiang Middle Road, Shanghai 200071, China. iceroser@126.com
Received: January 26, 2026 Revised: February 25, 2026 Accepted: March 24, 2026 Published online: July 21, 2026 Processing time: 163 Days and 10.9 Hours
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) has no significant impact on liver-metastatic patterns or survival outcomes in patients with pancreatic cancer. While the negative findings are clinically appealing, several issues may limit a definitive biological interpretation. First, the use of steatosis-weighted, noninvasive surrogates may be prone to misclassification in pancreatic cancer, where cachexia, sarcopenia, and systemic inflammation can distort these components, thereby attenuating true associations toward the null. Second, accumulating evidence has suggested that MASLD is highly heterogeneous, in which adverse oncologic outcomes are more consistently linked to metabolic inflammation and fibrosis rather than steatosis alone and pooling these phenotypes may dilute signals from high-risk subgroups. Third, in pancreatic cancer with short survival, death is a major competing event, conventional time-to-event analyses without competing-risk frameworks may thereby underestimate the metastasis-related effect. Additionally, mechanistic research supports the concept of a pre-metastatic hepatic niche that is driven by inflammation and metabolic reprogramming in pancreatic cancer. Therefore, we conclude that the statistical absence of correlation should not be conflated with the absence of biological causation. Instead, future studies incorporating fibrosis-focused phenotyping, treatment-aware modeling, and competing-risk analyses are warranted to clarify which MASLD subtypes may meaningfully influence metastasis and survival.
Core Tip: This article challenges the conclusion that metabolic dysfunction-associated steatotic liver disease is irrelevant to pancreatic cancer outcomes. We argue that the reported lack of association stems from the use of noninvasive surrogates that fail to capture the complexity of metabolic inflammation in cachectic patients. By ignoring the heterogeneity of metabolic dysfunction-associated steatotic liver disease and the statistical impact of competing risks, current analyses likely underestimate the pro-metastatic potential of the fibrotic liver niche. Furthermore, by contrasting these limitations with mechanistic evidence of a pre-metastatic niche, we emphasize that statistical absence of correlation does not equal biological absence of causation, advocating for fibrosis-focused future research.
