Association between Helicobacter pylori infection and the severity of metabolic dysfunction-associated fatty liver disease: a large-scale cross-sectional study

Background The relationship between Helicobacter pylori (H. pylori) infection and metabolic dysfunction-associated fatty liver disease (MAFLD) has garnered increasing attention; however, its correlation with disease severity remains inadequately characterized. This study aimed to investigate the association between H. pylori infection and the severity of MAFLD in a large Chinese cohort. Methods This cross-sectional study consecutively enrolled 2,610 patients diagnosed with MAFLD at the Department of Gastroenterology, The Third People's Hospital of Yunnan Province, between January 2023 and June 2025. Patients were stratified into mild, moderate, and severe MAFLD groups based on abdominal ultrasound findings and further categorized according to H. pylori status determined by ¹³C/¹⁴C-urea breath test. Clinical characteristics, metabolic profiles, and laboratory parameters were compared. Multivariate logistic regression analysis was employed to identify independent risk factors for MAFLD progression. Results Among the 2,610 participants (71.9% male; mean age 47.8 ± 11.6 years), the overall prevalence of H. pylori infection was 28.2%. Patients in the H. pylori-positive group exhibited significantly higher levels of fasting glucose (GLU), white blood cell count (WBC), and neutrophil count (NE) compared to the negative group (all P < 0.05). In subgroup analyses stratified by MAFLD severity, aspartate aminotransferase (AST) levels were consistently higher in H. pylori-positive patients across all severity grades (all P < 0.05). H. pylori positivity was associated with elevated WBC and lymphocyte (LYM) counts in the mild MAFLD group; higher alanine aminotransferase (ALT) and total cholesterol (TC) in the moderate group; and higher ALT and LYM in the severe group (all P < 0.05). A strong positive correlation was observed between H. pylori infection and MAFLD severity (*r* = 0.638, P < 0.001). Multivariate logistic regression confirmed H. pylori infection as an independent risk factor for severe MAFLD (mild vs. severe: OR = 297.00, 95% CI: 92.13–957.48, P < 0.001; moderate vs. severe: OR = 21.57, 95% CI: 5.91–78.75, P < 0.001). High-density lipoprotein cholesterol (HDL-C) and TC were also independently associated with MAFLD severity. Conclusions H. pylori infection is significantly and independently associated with the severity of MAFLD. The elevated GLU, WBC, and NE levels in infected patients suggest that H. pylori may exacerbate MAFLD through mechanisms involving glycemic dysregulation and low-grade systemic inflammation. Screening for H. pylori infection may have clinical utility in the risk stratification of patients with MAFLD.