Helicobacter pylori infection and metabolic dysfunction-associated steatotic liver disease: a prospective study and meta-analysis

BACKGROUND: Helicobacter pylori (H. pylori) infection and metabolic dysfunction-associated steatotic liver disease (MASLD) are significant global health concerns, but their association remains unclear, with evidence mainly from cross-sectional studies and Asian populations. METHODS: We analyzed UK Biobank (UKB) participants aged 40-69 years with objectively measured H. pylori serostatus data (N=4,246). Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for demographic, lifestyle, and cardiometabolic factors. We meta-analyzed seven prospective cohorts (all from non-European populations) and the UKB (8 cohorts in total with 36,145 participants and 6,979 cases) to evaluate the association between H. pylori seropositivity and MASLD risk. RESULTS: About 35.1% of the participants were seropositive for H. pylori in the UKB. With median follow-up of 11.1 years, we identified 32 MASLD cases. H. pylori seropositivity was marginally associated with higher MASLD risk (HR, 1.88; 95% CI, 0.92-3.82), whereas CagA seropositivity was significantly associated with higher risk (2.40; 1.17-4.92). Participants seropositive for both H. pylori and CagA had a higher MASLD risk than participants seronegative for both markers (2.58; 1.19-5.61). The meta-analysis showed that H. pylori was associated with a 24% higher MASLD risk (Risk Ratio, 1.24; 95% CI, 1.17-1.31). CONCLUSIONS: H. pylori infection, especially CagA seropositivity, was associated with higher MASLD risk in prospective studies. IMPACT: Our findings support a potential role of H. pylori virulence serology (CagA) in MASLD development. If confirmed, these findings could have implications for risk stratification and inform targeted eradication or prevention strategies.