The interplay between Helicobacter pylori infection and rs738409 PNPLA3 in metabolic dysfunction-associated steatotic liver disease

PLoS One. 2024 Sep 23;19(9):e0310361. doi: 10.1371/journal.pone.0310361. eCollection 2024.

Abstract

Background: Recent studies have suggested an association between H. pylori and metabolic-disfunction associated fatty liver disease (MASLD). However, epidemiologic studies have yielded inconsistent results. We aim to evaluate the association of H. pylori and G-allele PNPLA3 in MASLD diagnosis, and markers of severity.

Methods: A multi-center cross-sectional study was conducted. A total 224 functional dyspepsia (FD) patients cohort who underwent gastroscopy was selected. Biochemical, clinical parameters, ultrasound, FIB-4 score, LSM by VCTE, gastric biopsies, H. pylori status, and rs738409 PNPLA3 were evaluated. A second retrospective cohort of 86 patients with biopsy-proven MASLD who underwent gastroscopy with gastric biopsies was analyzed.

Results: In the FD cohort MASLD was observed in 52%, and H. pylori-positive in 51%. H. pylori infection was associated with MASLD prevalence, but in multivariate analyses adjusted for G-allele PNPLA3, it became not significant. Then in MASLD-only dyspeptic cohort, H. pylori infection was significantly linked to elevated serum AST levels and increased liver stiffness measurements, suggesting a potential role in liver injury and fibrosis. Histopathological analysis in biopsy-proven MASLD patients further supported these findings, showing a significant association between H. pylori infection and increased NAS score, fibrosis stage, and prevalence of MASH. Notably, the combination of H. pylori infection and G-allele PNPLA3 appeared to exacerbate MASLD severity beyond individual effects.

Conclusions: Our results suggest that H. pylori infection may play a role in the progression of liver injury and fibrosis in patients with MASLD, especially in those with specific genetic predispositions.

Publication types

  • Multicenter Study

MeSH terms

  • Acyltransferases
  • Adult
  • Alleles
  • Cross-Sectional Studies
  • Dyspepsia / complications
  • Dyspepsia / genetics
  • Dyspepsia / microbiology
  • Fatty Liver / complications
  • Fatty Liver / genetics
  • Female
  • Helicobacter Infections* / complications
  • Helicobacter Infections* / genetics
  • Helicobacter pylori*
  • Humans
  • Lipase* / genetics
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Membrane Proteins* / genetics
  • Middle Aged
  • Phospholipases A2, Calcium-Independent
  • Polymorphism, Single Nucleotide
  • Retrospective Studies

Substances

  • PNPLA3 protein, human
  • Lipase
  • Membrane Proteins
  • Acyltransferases
  • Phospholipases A2, Calcium-Independent