MetALD Was an Independent Risk Factor for the Recurrence of Early Esophageal Squamous Cell Carcinoma After Endoscopic Resection: A Multicenter Cohort Study Using Directed Acyclic Graphs.

BACKGROUND

Alcohol consumption and metabolic dysfunction are risk factors for esophageal squamous cell carcinoma (ESCC); however, their combined effects on recurrence remain unclear. This study aimed to evaluate whether metabolic dysfunction-associated steatotic liver disease (MASLD) with moderate alcohol intake (MetALD) independently contributes to ESCC recurrence following curative endoscopic submucosal dissection (ESD).

METHODS

We conducted a multicenter cohort study involving 63 moderate drinkers with early-stage ESCC who underwent curative ESD. MetALD was defined as MASLD with moderate alcohol consumption. Recurrence-free survival was compared between patients with MetALD and those without steatotic liver disease. Multivariable Cox regression, decision tree, random forest analyses, and directed acyclic graphs assessed independent predictors of recurrence.

RESULTS

During a median follow-up of 2.3 years, 25.4% of patients experienced recurrence. Multivariable analyses identified alcohol non-abstinence and MetALD as independent predictors. In supplementary analyses, hepatic steatosis and alcohol non-abstinence-but not metabolic dysfunction alone-were significantly associated with recurrence. Decision tree and random forest analyses highlighted alcohol non-abstinence and MetALD as the most influential predictors. Directed acyclic graphs demonstrated direct causal pathways from both factors to ESCC recurrence. Among non-abstinent patients, those with MetALD had a markedly higher recurrence rate (54%) compared with moderate drinkers without SLD (27%), underscoring the synergistic oncogenic effect of alcohol and metabolic dysfunction.

CONCLUSIONS

MetALD is an independent risk factor for ESCC recurrence after curative ESD, especially among non-abstainers. These findings suggest the synergistic oncogenic potential of moderate alcohol intake and MASLD, and underscore the importance of lifestyle and metabolic interventions in post-ESD management.