Impact of metabolic dysfunction-associated fatty liver disease on the incidence of Helicobacter pylori-negative gastric cancer

Tomoyuki Nakane; Shuhei Fukunaga; Dan Nakano; Tsubasa Tsutsumi; Hiroshi Tanaka; Tomonori Chou; Shinpei Minami; Akihiro Ohuchi; Tsutomu Nagata; Kota Takaki; Hiroshi Takaki; Ichiro Miyajima; Ryuichi Nouno; Shinobu Yoshinaga; Michita Mukasa; Yoshinobu Okabe; Takumi Kawaguchi

doi:10.1111/hepr.14010

Impact of metabolic dysfunction-associated fatty liver disease on the incidence of Helicobacter pylori-negative gastric cancer

Hepatol Res. 2023 Dec 29. doi: 10.1111/hepr.14010. Online ahead of print.

Authors

Tomoyuki Nakane¹, Shuhei Fukunaga¹, Dan Nakano¹, Tsubasa Tsutsumi¹, Hiroshi Tanaka¹, Tomonori Chou¹, Shinpei Minami¹, Akihiro Ohuchi¹, Tsutomu Nagata¹, Kota Takaki², Hiroshi Takaki², Ichiro Miyajima², Ryuichi Nouno², Shinobu Yoshinaga³, Michita Mukasa¹, Yoshinobu Okabe¹, Takumi Kawaguchi¹

Affiliations

¹ Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
² Division of Gastroenterology, Department of Medicine, Kumamoto Central Hospital, Kikuchi, Japan.
³ Medical Examination Section, Medical Examination Part Facilities, Public Utility Foundation Saga Prefectural Health Promotion Foundation, Saga, Japan.

PMID: 38156966
DOI: 10.1111/hepr.14010

Abstract

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 = 1078) and health checkup examinees (n = 17 408). We analyzed patients with HPNGC (n = 26) and healthy participants with no H. pylori infection or any abnormal findings on upper gastrointestinal endoscopy (n = 1130). 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% (26/1078) 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. Metabolic dysfunction-associated fatty liver disease was also identified as the most important classifier for the presence of HPNGC in decision-tree analyses. Helicobacter pylori-negative gastric cancer 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: Metabolic dysfunction-associated fatty liver disease was the most influential independent factor associated with HPNGC. These findings suggest that fatty liver and metabolic dysfunction could be involved in the pathogenesis of HPNGC.

Keywords: Helicobacter pylori; clinicopathologic features; early gastric cancer; endoscopic submucosal dissection; uninfected.

Grants and funding

JP23fk0210090/Japan Agency for Medical Research and Development