Data from <i>Helicobacter pylori</i> Infection and Metabolic Dysfunction–Associated Steatotic Liver Disease: A Prospective Study and Meta-Analysis

<jats:p>&lt;div&gt;Abstract Background:&lt;p&gt;&lt;i&gt;Helicobacter pylori&lt;/i&gt; 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.&lt;/p&gt; Methods:&lt;p&gt;We analyzed UK Biobank (UKB) participants ages 40 to 69 years with objectively measured &lt;i&gt;H. pylori&lt;/i&gt; serostatus data (&lt;i&gt;N&lt;/i&gt; = 4,246). Cox models estimated hazard ratios (HR) and 95% confidence intervals (CI), 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 &lt;i&gt;H. pylori&lt;/i&gt; seropositivity and MASLD risk.&lt;/p&gt; Results:&lt;p&gt;About 35.1% of the participants were seropositive for &lt;i&gt;H. pylori&lt;/i&gt; in the UKB. With a median follow-up of 11.1 years, we identified 32 MASLD cases. &lt;i&gt;H. pylori&lt;/i&gt; seropositivity was marginally associated with higher MASLD risk (HR, 1.88; 95% CI, 0.92–3.82), whereas cytotoxin-associated gene A (&lt;i&gt;CagA&lt;/i&gt;) seropositivity was significantly associated with higher risk (2.40; 1.17–4.92). Participants seropositive for both &lt;i&gt;H. pylori&lt;/i&gt; and &lt;i&gt;CagA&lt;/i&gt; had a higher MASLD risk than participants seronegative for both markers (2.58; 1.19–5.61). The meta-analysis showed that &lt;i&gt;H. pylori&lt;/i&gt; was associated with a 24% higher MASLD risk (risk ratio, 1.24; 95% CI, 1.17–1.31).&lt;/p&gt; Conclusions:&lt;p&gt;&lt;i&gt;H. pylori&lt;/i&gt; infection, particularly &lt;i&gt;CagA&lt;/i&gt; seropositivity, was associated with higher MASLD risk in prospective studies.&lt;/p&gt; Impact:&lt;p&gt;Our findings support a potential role of &lt;i&gt;H. pylori&lt;/i&gt; virulence serology (&lt;i&gt;CagA&lt;/i&gt;) in MASLD development. If confirmed, these findings could have implications for risk stratification and inform targeted eradication or prevention strategies.&lt;/p&gt;&lt;/div&gt;</jats:p>