Impact of MAFLD on the Incidence of Helicobacter pylori‐negative Gastric Cancer

Aim

The incidence of Helicobacter pylori‐negative gastric cancer (HPNGC) is increasing worldwide. Recently, metabolic dysfunction‐associated fatty liver disease (MAFLD) has been reported to be associated with various cancers, but its association with HPNGC has not been reported. We aimed to identify important independent factors associated with HPNGC, including MAFLD.

Methods

This multicenter observational cohort study enrolled patients with gastric cancer (n=1,078) and health checkup examinees (n=17,408). We analyzed patients with HPNGC (n=26) and healthy participants with no Helicobacter pylori infection or any abnormal findings on upper gastrointestinal endoscopy (n=1,130). A logistic regression model was used to identify independent factors associated with HPNGC. The priority of the factors associated with HPNGC was evaluated using a decision tree algorithm and random forest analysis.

Results

Among all patients with gastric cancer, 2.4% (26/1,078) were diagnosed with HPNGC (mean age, 64 years; male/female, 13/13). In the logistic regression analysis, age, smoking, and MAFLD (odds ratio, 6.5359; 95% confidence interval, 2.5451–16.7841; p<0.0001) were identified as independent factors associated with HPNGC. MAFLD was also identified as the most important classifier for the presence of HPNGC in decision tree analyses. HPNGC was observed in 5.2% of patients with MAFLD and 0.8% of patients without MAFLD. In the random forest analysis of the HPNGC, MAFLD was identified as the distinguishing factor with the highest variable importance (0.32).

Conclusions

MAFLD was the most influential independent factor associated with HPNGC. These findings suggest that fatty liver and metabolic dysfunction may be involved in the pathogenesis of HPNGC.

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