Helicobacter pylori cagA/vacAs1-m1 strain is associated with high risk of fibrosis in metabolic-dysfunction-associated steatotic liver disease

Introduction and Objectives: Recent studies have suggested an association between H. pylori and metabolic dysfunction associated steatotic liver disease (MASLD). We aim to evaluate the association of H. pylori virulence genes with non-invasive markers of liver injury and fibrosis in MASLD subjects.Patients and Methods: A total of 362 dyspeptic patients who underwent gastroscopy were selected. Biochemical, clinical parameters, ultrasound, FIB-4 score, liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE), gastric biopsies, and H. pylori virulence genes (cagA, vacA) were evaluated.Results: A cohort comprised of 61 % women and 39 % men with a median age of 52 (40−60) years. MASLD was observed in 42 %, and H. pylori-positive in 45 %. No differences were observed regarding H. pylori status at comorbid metabolic conditions. In MASLD cohort, H. pylori-positive was associated with higher AST, ALT, FIB-4 and LSM. Indeed, carriers of cagA/vacA-s1/m1-positive allelic combination were associated with higher AST, ALT, FIB-4 and LSM but not cagA/vacA-s1/m1-negative. The OR for high-risk of significant/advanced- fibrosis by VCTE (8 kPa) with H. pylori-positive was 2.56 (95 % CI, 1.2−5.75) and for cagA/vacA-s1/-m1-positive allelic carriers was 4.01 (95 % CI, 1.38−11.56), but non-significant association in cagA/vacA-s1/-m1-negative. After adjusting for age, gender, diabetes, BMI and hypertension the OR for VCTE 8 kPa with H. pylori-positive was 2.43 (95 % CI, 1.88−12.44), and cagA/vacA-s1/m1-positive allelic carriers was 4.06 (95 % CI, 1.22−14.49).Conclusions: In our cohort of FD patients with MASLD, H. pylori was associated with non-invasive markers of liver injury and fibrosis. Carriers of cagA/vacA-s1/m1-positive allelic combination showed an independent risk of significant/advanced fibrosis by VCTE.Fil: Maiorana, Facundo Nicolás. Universidad Nacional de Misiones. Facultad de Ciencias Exactas Químicas y Naturales. Departamento de Bioquímica Clínica. Laboratorio de Biotecnología Molecular; ArgentinaFil: Neschuk, Magali. Universidad Nacional de Misiones. Facultad de Ciencias Exactas Químicas y Naturales. Departamento de Bioquímica Clínica. Laboratorio de Biotecnología Molecular; ArgentinaFil: Caronia, María Virginia. Universidad Nacional de Misiones. Facultad de Ciencias Exactas Químicas y Naturales. Departamento de Bioquímica Clínica. Laboratorio de Biotecnología Molecular; ArgentinaFil: Elizondo, Karina. Instituto Universidad de la Fundación "Héctor Barceló"; ArgentinaFil: Schneider, Adolfo. Instituto Universidad de la Fundación "Héctor Barceló"; ArgentinaFil: Veron, Georgina. Instituto Universidad de la Fundación "Héctor Barceló"; ArgentinaFil: Zapata, Pedro Dario. Universidad Nacional de Misiones. Facultad de Ciencias Exactas Químicas y Naturales. Departamento de Bioquímica Clínica. Laboratorio de Biotecnología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; ArgentinaFil: Barreyro, Fernando Javier. Universidad Nacional de Misiones. Facultad de Ciencias Exactas Químicas y Naturales. Departamento de Bioquímica Clínica. Laboratorio de Biotecnología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentin

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

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.Fil: Maiorana, Facundo. Universidad Nacional de Misiones. Facultad de Cs.exactas Químicas y Naturales. Departamento de Bioquímica Clinica; ArgentinaFil: Neschuk, Magali. Universidad Nacional de Misiones. Facultad de Cs.exactas Químicas y Naturales. Departamento de Bioquímica Clinica; ArgentinaFil: Caronia, María Virginia. Universidad Nacional de Misiones. Facultad de Cs.exactas Químicas y Naturales. Departamento de Bioquímica Clinica; ArgentinaFil: Elizondo, Karina. Instituto Universidad de la Fundación "Héctor Barceló"; ArgentinaFil: Robledo, María Laura. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Patología; ArgentinaFil: Schneider, Adolfo. Instituto Universidad de la Fundación "Héctor Barceló"; ArgentinaFil: Veron, Georgina. Instituto Universidad de la Fundación "Héctor Barceló"; ArgentinaFil: Zapata, Pedro Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina. Universidad Nacional de Misiones. Facultad de Cs.exactas Químicas y Naturales. Departamento de Bioquímica Clinica; ArgentinaFil: Barreyro, Fernando Javier. Universidad Nacional de Misiones. Facultad de Cs.exactas Químicas y Naturales. Departamento de Bioquímica Clinica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentin