Persistently Active Helicobacter pylori Infection Is Associated with the Development of Metabolic Dysfunction-Associated Steatotic Liver Disease

<b>Background/Objectives:</b> Previous studies suggested a link between <i>Helicobacter pylori</i> (<i>H. pylori)</i> infection and steatotic liver disease, now termed metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to identify the association of active <i>H. pylori</i> infection and the new concept of MASLD in a longitudinal cohort. <b>Methods:</b> We reviewed 1497 health examinees who had two endoscopic biopsies for <i>H. pylori</i> activity without hepatic steatosis at the baseline abdominal ultrasonography. Subjects were classified into four groups based on <i>H. pylori</i> activity. Multivariable Cox models assessed the link between active <i>H. pylori</i> infection status and incident MASLD. <b>Results:</b> Over a median follow-up of 31.1 months, 247 subjects (16.5%) developed MASLD. The groups were: <i>H. pylori</i> naïve (n = 57, 15.6%), de novo (n = 31, 15.3%), eradicated (n = 32, 16.1%), and persistent (n = 127, 17.4%). The <i>H. pylori</i> persistent group had a higher risk of MASLD compared to naïve group (hazard ratio: 1.41; 95% confidence interval: 1.01-1.96; <i>p</i>-value = 0.045). The association between <i>H. pylori</i> infection and incident MASLD was significant only with ongoing infection. <b>Conclusions:</b> Persistent <i>H. pylori</i> infection increases the risk of MASLD, indicating that active infection may contribute to MASLD development. Eradicating active <i>H. pylori</i> infection might help lower the incidence of MASLD.