Helicobacter pylori infection as a contributing factor to metabolic dysfunction-associated steatohepatitis: A population-based insight

Abstract

This letter discusses the research conducted by Abdel-Razeq et al, highlighting a significant association between Helicobacter pylori (H. pylori) infection and metabolic dysfunction-associated steatohepatitis (MASH) in individuals with a prior history of H. pylori infection. Using a comprehensive patient database, the study establishes an independent correlation between H. pylori and an elevated risk of MASH, even after adjusting for coexisting conditions such as obesity, type 2 diabetes, and dyslipidemia. Notably, the findings suggest that H. pylori may worsen liver pathology through inflammatory pathways, contributing to hepatic insulin resistance and lipid accumulation. Although the study provides strong evidence for this association, limitations related to diagnostic heterogeneity indicate a need for further research to clarify the underlying mechanisms and to explore the potential roles of genetic and microbiome factors in this relationship.

Key Words: Helicobacter pylori; Inflammation; Insulin resistance; Liver pathology; Metabolic dysfunction-associated steatohepatitis

Core Tip: Helicobacter pylori (H. pylori) infection may play an independent role in the development of metabolic dysfunction-associated steatohepatitis, underscoring its influence beyond gastric disease. This association remains significant even after adjusting for key metabolic risk factors, including obesity, type 2 diabetes, and dyslipidemia, suggesting that H. pylori could intensify liver inflammation and insulin resistance through inflammatory pathways, leading to hepatic lipid accumulation. These findings provide a basis for future research into genetic and microbiome-related factors that may modulate the impact of H. pylori on liver pathology, potentially paving the way for targeted interventions in patients vulnerable to metabolic liver disease.

TO THE EDITOR

I read with great interest the study by Abdel-Razeq et al[1], published in the World Journal of Hepatology. This study makes a substantial contribution to our understanding of the link between Helicobacter pylori (H. pylori) infection and metabolic dysfunction-associated steatohepatitis (MASH), particularly within the framework of non-alcoholic fatty liver disease (NAFLD). Given the global rise in both H. pylori infections and MASH, these findings have important public health and clinical implications, especially as we seek to uncover potential mechanisms through which H. pylori may aggravate liver pathology via metabolic pathways.

The study utilizes an extensive multicenter database of over 69 million patients, enabling a robust analysis of the prevalence and risk factors linked to MASH in individuals with a history of H. pylori infection. The authors demonstrate that, even after adjusting for major confounders including obesity, type 2 diabetes mellitus (T2DM), dyslipidemia, and hypertension-H. pylori infection remains independently associated with a significantly higher risk of developing MASH, with an odds ratio of 2.51 (95% confidence interval: 2.31-2.73). This association holds even when accounting for lifestyle and demographic variables, underscoring a potential direct role of H. pylori in MASH pathogenesis[1].

A major strength of this study lies in its rigorous approach to controlling for confounding variables. The authors carefully accounted for key comorbidities often associated with both H. pylori infection and MASH, including obesity and components of metabolic syndrome. This method strengthens the study’s internal validity and supports the conclusion that H. pylori infection may play an independent role in MASH progression. However, while these findings are compelling, further research is essential to clarify the specific mechanisms through which H. pylori might contribute to liver inflammation and fibrosis. Previous studies have demonstrated that H. pylori infection can trigger a low-grade systemic inflammatory response mediated by pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). This inflammatory response may contribute to insulin resistance in the liver and lipid accumulation in hepatocytes[2]. Specifically, H. pylori infection raises the levels of TNF-α and IL-6, which disrupt insulin signaling by inhibiting the tyrosine phosphorylation of insulin receptor substrates while promoting their serine phosphorylation[3].

Furthermore, a chronic inflammatory state can lead to abnormalities in lipid metabolism, resulting in increased lipid accumulation in the liver. This condition is closely associated with the development of NAFLD, which is further linked to an elevated risk of insulin resistance and diabetes[2,4]. Consequently, H. pylori infection not only affects gastric health but may also exacerbate pathological conditions such as chronic hepatitis, liver fibrosis, and cirrhosis, thereby negatively impacting liver function[5,6]. This underscores the urgent need for early detection and treatment of H. pylori infection to prevent and manage related metabolic diseases.

Additionally, the study’s large sample size and broad geographic representation provide valuable insights into the epidemiological patterns of MASH and H. pylori infection across the United States. Notably, the prevalence of metabolic comorbidities, such as obesity and T2DM, was significantly higher among MASH patients with H. pylori infection compared to controls, highlighting strong associations with these conditions. This finding aligns with previous research suggesting that H. pylori may influence lipid metabolism and insulin sensitivity, potentially through modifications in gut microbiota or changes in adipokine profiles that drive liver fat accumulation and inflammation. Future studies should explore the role of gut-liver axis dysbiosis in H. pylori-positive MASH patients, focusing on how alterations in the microbiome contribute to systemic inflammation and liver damage.

One limitation of this study, as noted by the authors, is the use of varied diagnostic methods for H. pylori infection, including enzyme-linked immunosorbent assay and urease breath tests, which may introduce heterogeneity in diagnostic accuracy. Additionally, reliance on non-invasive diagnostic methods for MASH, such as ultrasonography, could lead to potential misclassification bias. As liver biopsy remains the gold standard for diagnosing MASH, future research should prioritize standardized diagnostic criteria to enhance comparability across patient cohorts.

Another area for further investigation is the potential role of genetic factors in modulating the relationship between H. pylori and MASH. Genetic predispositions to metabolic syndrome or heightened inflammatory responses may amplify the impact of H. pylori on liver pathology[7]. For instance, polymorphisms in genes encoding cytokines or adipokines could affect the extent of hepatic inflammation and fibrosis in H. pylori-infected individuals[8]. Identifying genetic markers linked to increased susceptibility to MASH in the context of H. pylori infection could enable more effective risk stratification and support personalized treatment approaches[7,8].

The authors also acknowledge conflicting findings in the literature regarding the association between H. pylori and NAFLD-related liver disease, with some studies reporting no significant link. These inconsistencies may stem from variations in study populations, diagnostic criteria, and geographic differences in H. pylori strains. For instance, virulence factors such as cytotoxin-associated gene A and vacuolating cytotoxin A differ among strains and have been associated with varying degrees of systemic inflammation and metabolic dysregulation[9,10]. Future studies could benefit from stratifying patients based on H. pylori strain virulence, which may help reconcile these discrepancies and provide a more detailed understanding of the H. pylori-MASH association[11].

CONCLUSION

In conclusion, Abdel-Razeq et al[1] present a valuable population-based analysis linking H. pylori infection to an elevated risk of MASH, expanding our understanding of the potential extra-gastric effects of H. pylori. Their findings highlight the need for further exploration of the biological mechanisms underlying this association and suggest that H. pylori eradication might offer therapeutic benefits for patients at risk of MASH. Given the widespread prevalence of H. pylori infection worldwide, especially in developing countries, it is essential to deepen our understanding of its role in liver pathology[12]. This knowledge not only sheds light on the potential impact of H. pylori on NAFLD and related liver conditions but also opens new avenues for their prevention and management. By elucidating the association between H. pylori infection and liver metabolic disorders, we can gain valuable insights into its role in the pathogenesis of metabolic liver diseases. Moreover, this research establishes a foundation for future longitudinal and interventional studies aimed at investigating the clinical effects of H. pylori treatment in NAFLD patients. Ultimately, these efforts have the potential to reshape current clinical guidelines regarding H. pylori management in individuals with metabolic liver disease, offering innovative strategies and perspectives to enhance overall patient health.