Helicobacter pylori (HP) is a Gram-negative microaerophilic bacterium that mainly invades the gastroduodenal wall and can cause inflammation and ulceration up to malignant transformation of the mucosa. It can also cause many intestinal and extra intestinal complications. It was discovered in 1982 and since then its prevalence is increasing and widespread mainly in developing countries [18].
Nonalcoholic fatty liver disease (NAFLD) is one of the most important hepatic diseases that were studied. It is defined as hepatic steatosis in ≥ 5% of hepatocytes in patients with no or little alcohol intake. It is divided into NAFL or simple steatosis, which often not complicated with cirrhosis or HCC, and nonalcoholic steatohepatitis (NASH) which may progress to complications [19, 20].
Insulin resistance is a corner stone in MET S beside high blood pressure and abnormal cholesterol levels as it is a cluster of metabolic derangements that can lead to many complications including increased risk of DM type II and risk of heart diseases [11]. The main components for diagnosis of MET S are elevated serum triglycerides, elevated blood pressure, fasting blood glucose, increased waist circumference as an indicator for upper body obesity, and decreased high-density lipoproteins levels obtained from the recent accepted consensus [4]. We need 3 or more of these factors for diagnosis. NAFLD is considered the hepatic component of metabolic syndrome [21].
There has been speculations regarding the possible association of HP infection and development of NAFLD, which is usually associated with obesity, diabetes, and cardiovascular diseases [22].
This study was conducted to evaluate the possible association between H. pylori infection and metabolic syndrome especially with the presence of nonalcoholic fatty liver disease, and to explore if there is a possible role of HP infection in NAFL occurrence and progression especially in the presence of other metabolic abnormalities of MET S.
The study included 300 patients of which metabolic syndrome patients (200 patients) were selected according to recent criteria of Alberti et al. [4] and further subdivided into 2 groups according to the presence or absence of NAFLD, in addition to 100 age-matched healthy controls. All patients were subjected to full history taking and clinical examination laboratory investigations for diagnosis of MET S. All MET S patients had abdominal ultrasonography for detection of hepatic steatosis. NAFLD fibrosis risk score was calculated online for MET S patients with NAFLD to discover patients with marked fibrosis—according to Angulo et al. [16] which divided the patients into NO or mild fibrosis (F0–F2) and marked fibrosis (F3–F4) that might progress to NASH. H. pylori stool antigen (SAT) testing was done in all subjects.
Prevalence of HP infection in all study subjects was 57.7%; this is in agreement with Hooi et al. [23] who reported in their systematic review and meta-analysis that more than half of world population have H. pylori infection. Moreover, Eshraghian [13] reported that prevalence of HP infection is increasing in developing countries, and in some areas, it may reach 80%. Also, in our study, rural patients showed significantly higher prevalence of HP infection than urbans especially in MET S with NAFLD group (Table 5). Muhsen et al. [24] attributed that to low socioeconomic level and bad hygienic conditions which are the major risk factors for intrafamilial transmission of HP infection. Regarding gender differences, some studies showed no difference [25], while others [26] found a male predominance of HP infection in Hyderabad, and Agah et al. [27] found female predominance in HP-induced gastric ulcer. Our study found no gender difference.
In this study, we found that HP infection was more frequent in MET S with NAFLD patients (73%) than in MET S without NAFLD (47%) (Table 4), suggesting that HP infection might be associated with the risk of NAFLD development in those patients. In agreement with our results, Abdel-Razik et al. [28] reported in their study that HP infection increased the risk of NAFLD. Moreover, they suggested that IR, inflammatory mediators, and disturbance in lipid metabolism associated with HP infection are the main mechanisms of NAFLD development. They suggested that eradication of HP might reduce NAFLD risk. In contrast to our study, Okushin et al. [12] reported through logistic regression that HP infection was not associated with NAFLD, that may be due to studying many other variants as BMI, platelet count, and ALT and not focusing on HP infection.
In this study, 60% of MET S patients were HP positive compared to controls, with statistical significance (Table 4). Other studies [29] found a positive correlation between HP infection and MET S. Moreover, Lim et al. [30] suggested that H. pylori infection may play an independent role in the pathogenesis of metabolic syndrome in patients under 65 years old.
Regarding clinical characteristics of the patients, we found significantly higher values of body weight, BMI, and waist circumference in patients having MET S patients with NAFLD than those without NAFLD (Table 2) which is in agreement with previous studies [12, 31]. Our study shows a statistically significant association between elevated triglycerides, cholesterol, and LDL, and low HDL levels, and NAFLD (Table 3). Also, we found that uncontrolled hyperglycemia is positively associated with NAFLD (Table 3), which is in agreement with previous studies of Friedman et al. [32] who reported that the main metabolic abnormalities predisposing to NAFLD are hyperglycemia, dyslipidemia, IR, and obesity. Also, a positive association between HP infection and elevated S.TGs, cholesterol levels and hyperglycemia was noticed in our study (Table 7).
Regarding the degree of fibrosis in patients of MET S with NAFLD, using fibrosis risk score [16], we found that HP infection is associated with increased degree of fibrosis significantly (Table 6) with progression to marked fibrosis which may complicate with NASH with overall predictive value of 75% (Table 8) especially in patients with hyperglycemia. That is supported by the study done by Shen et al. [33] who reported that IR resulting from lipid metabolic disturbances and fatty acids accumulation in liver is the main modulator and link between HP infection and hepatic steatosis. Also, the study done by Doğan et al. [34] supports our results as they declared that H. pylori infection is strongly linked to the pathogenesis of early-stage NAFLD, which is described as simple steatosis. On the other hand, Polyzos et al. [10] indicated that H. pylori infection may not contribute to the progression of NAFL to NASH.
From the previous discussion, it is clear that HP infection is positively associated with occurrence and progression rate of hepatic steatosis (nonalcoholic fatty liver) especially in MET S patients. So, it can be suggested also that testing and eradication of H. pylori infection might be indicated in patients having metabolic syndrome which could have a role in decreasing the occurrence as well as the burden of NAFLD in such patients.
However, this study has limitations being a case control study, so further prospective studies are needed to confirm the role of HP in progression of NAFL to NASH in patients with metabolic syndrome.