Relationship Of Helicobacter Pylori Infection With Nonalcoholic Fatty Liver Disease: A Meta-analysis

Background and aimsHelicobacter pylori(H.pylori)infection is associated with metabolic syndrome,atherosclerosis,cardiovascular disease and diabetes.H.Pylori infection may play a pathogenic role in the development of oxidative stress,immune cross reaction,elevated blood pressure,changes in blood lipid level,impaired glucose tolerance and insulin resistance.Nonalcoholic fatty liver disease(NAFLD)is closely related to obesity,type2 diabetes,insulin resistance,dyslipidemia and hypertension,which form a series of metabolic disorders.Research shows H.Pylori infection plays a crucial role in the development of liver cell injury and non-cancerous and malignant liver diseases including NAFLD.This is due to a variety of mechanisms,the most important of which is that the toxic products of H.Pylori and the oxidative damage of hepatocytes promote liver injury.Today,H.Pylori infection and NAFLD have gained more and more recognition,both of which have a serious impact on global human health.However,the association between H.pylori infection and NAFLD remains controversial.Therefore,we assessed the exact relationship between H.pylori infection and NAFLD by integrating all available data.MethodsPub Med,EMBASE and Cochrane library databases were searched.Only random effect models are used.For raw data,ORs and RRs with their 95%CIs were calculated.For data adjusted for confounders,a ORs and a HRs with their 95%CIs were calculated.Cochrane Q test and I~2 statistic were used for heterogeneity test,P<0.1 and/or I~2>50%was considered to be statistically significant heterogeneity.Subgroup and meta-regression analyses were performed in studies of corrected and unadjusted confounding factors to explore sources of heterogeneity.Detect interactions between subgroups.Sensitivity analyses were performed by omitting one study at a time.The Egger test was used to assess publication bias,and P<0.1 was considered to be significantly associated with publication bias.ResultsA total of 2025 articles were retrieved.After screening,34 studies and 218573 patients were finally included.Based on unadjusted data from 26 cross-sectional studies and 3case-control studies,H.pylori infection was significantly associated with NAFLD(OR=1.26,95%CI=1.17-1.36,P<0.001).Heterogeneity was statistically significant(I~2=88.7%;P<0.001).Subgroup analyses did not identify any source of heterogeneity.Meta-regression analyses showed that the study design(P<0.001)and diagnostic methods of NAFLD(P<0.001)might be the sources of heterogeneity.Sensitivity analyses did not identify any source of heterogeneity.Egger test did not show any significant publication bias(P=0.294).Based on adjusted data from 15 cross-sectional studies and 1 case-control study,H.pylori infection was significantly associated with NAFLD(a OR=1.25,95%CI=1.08-1.44,P<0.001).Heterogeneity was statistically significant(I2=90%,p<0.001).Subgroup analyses did not identify any source of heterogeneity.Meta-regression analyses showed that the study design(P=0.015)and diagnostic methods of NAFLD(P=0.023)might be the sources of heterogeneity.Sensitivity analyses did not identify any source of heterogeneity.Egger test did not show any significant publication bias(P=0.591).Compared with control subjects without NAFLD,patients with moderate(OR=1.67,95%CI=1.17-2.39,P=0.005)and severe(OR=1.71,95%CI=1.30-2.24,P<0.001)NAFLD,but not those with mild NAFLD(OR=1.14,95%CI=0.9-1.45,P=0.286),had significantly higher proportions of H.pylori infection.Based on the adjusted data from 3 cohort studies,the meta-analysis showed that H.pylori infection was associated with the occurrence of NAFLD(a HR=1.18,95%CI=1.05-1.34;P=0.007).Heterogeneity was statistically significant(I2=70.8%,P=0.032).Based on the unadjusted data from 3 cohort studies,the meta-analysis showed that H.pylori infection was not significantly associated with the occurrence of NAFLD(RR=1.41,95%CI=0.80-2.48;P=0.237).Heterogeneity was statistically significant(I2=98.3%,P<0.001).ConclusionsH.pylori infection is associated with NAFLD,especially moderate and severe NAFLD.Impact of H.pylori eradication on the prevention of NAFLD should be further explored.This may provide a new method for clinical prevention and treatment of NAFLD.