Association between Helicobacter pylori infection and risk of nonalcoholic fatty liver disease: An updated meta-analysis

Highlights

• The link between H. pylori infection and NAFLD has attracted considerable interest.

• It is currently uncertain whether H. pylori infection increases risk of NAFLD.

• In this meta-analysis H. pylori infection is associated with a higher risk of NAFLD.

• This risk is independent of age, sex, adiposity measures, smoking and diabetes.

Abstract

Background

Recent studies that have examined the association between Helicobacter pylori infection and risk of nonalcoholic fatty liver disease (NAFLD) have produced conflicting data. We have performed a systematic review and meta-analysis to assess the association between H. pylori infection and risk of NAFLD.

Methods

We searched PubMed, Web of Science and Scopus databases using predefined keywords to identify observational studies (published up to November 2018), in which NAFLD was diagnosed by histology, imaging or biochemistry. Data from selected studies were extracted and meta-analysis was performed using random-effects modeling. The statistical heterogeneity among studies (I²-index), subgroup analyses and the possibility of publication bias were assessed.

Results

Thirteen observational (11 cross-sectional/case-control and 2 longitudinal) studies involving a total of 81,162 middle-aged individuals of predominantly Asian ethnicity (47.5% of whom had H. pylori infection diagnosed by urea breath test, faecal or serological tests) were included in the final analysis. Meta-analysis of data from cross-sectional and case-control studies showed that H. pylori infection was associated with increased risk of prevalent NAFLD (n = 11 studies; random-effects odds ratio [OR] 1.20, 95% CI 1.07–1.35; I² = 59.6%); this risk remained significant in those studies where analysis was fully adjusted for age, sex, smoking, adiposity measures, diabetes or dyslipidemia (random-effects OR 1.19, 95% CI 1.07–1.32, I² = 0%). Meta-analysis of data from longitudinal studies showed that H. pylori infection was also associated with increased NAFLD incidence (n = 2 studies; random-effects hazard ratio 1.14, 95% CI 1.05–1.23; I² = 0%). Sensitivity analyses did not alter these findings. Funnel plot did not reveal significant publication bias.

Conclusions

H. pylori infection is associated with mildly increased risk of both prevalent and incident NAFLD in middle-aged individuals. More prospective studies, particularly in non-Asian populations, and mechanistic studies are required to better elucidate the link between chronic H. pylori infection and NAFLD.

Introduction

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver diseases in many parts of the world [[1], [2], [3]]. The global prevalence of NAFLD has been estimated to be nearly 25% with highest prevalence in the Middle East (31.8%) and Asia (27.4%) and lowest in Africa (13.5%) [2].

Growing evidence suggests that intestinal dysbiosis may be involved in NAFLD pathogenesis, mainly through its effects on innate immune system, gut permeability, intestinal production of short-chain fatty acids, and fermentation of indigestible carbohydrates [4,5]. Experimental evidence in animals is also emerging that there is a link between intestinal dysbiosis, evidence of Helicobacter pylori infection and NAFLD pathogenesis [[4], [5], [6], [7]]. H. pylori, a Gram-negative bacterium colonizing the gastric epithelium, is a cofactor in the development of peptic ulcers, gastric cancer and gastric mucosa-associated lymphoid-tissue lymphoma [6]. H. pylori infection represents one of the most frequent gastrointestinal infections in humans [6]. A comprehensive meta-analysis recently showed that H. pylori infection varies between different geographic locations, with greater prevalence in developing countries (e.g., ~50–65% in Asia and Latin America) than in developed countries (~20–35% in United States and Europe) [8]. Although the evidence is not conclusive, chronic H. pylori infection has been also associated with inflammatory bowel diseases, asthma and other allergic manifestations, as well as a variety of other extra-gastrointestinal conditions, including cardiovascular, hematologic and metabolic diseases [9].

In recent years, there has been growing scientific interest in the association between H. pylori infection and NAFLD in man [9,10]. Indeed, several observational studies have examined the association between H. pylori infection and risk of NAFLD in middle-aged individuals who were largely asymptomatic for peptic ulcers or functional dyspepsia, and who did not take H. pylori eradication therapy [[11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23]]. Since the findings of these observational studies have been inconsistent, it remains uncertain whether H. pylori infection is associated with increased risk of NAFLD.

In this systematic review and meta-analysis, we sought to investigate whether, and to what extent, H. pylori infection was associated with risk of NAFLD. Given the growing clinical and economic burden of NAFLD worldwide, we believe that clarification of the magnitude of potential adverse effects of H. pylori infection on NAFLD risk might also have clinical implications for the prevention and treatment of this common and burdensome disease.