**1. Introduction**

*Helicobacter pylori* (*H. pylori*) is a gram-negative aerobic bacteria, which was first discovered by Warren and Marshall in 1983. They proved that it can colonize and infect the highly acidic environment of the stomach. Later, they proved that *H. pylori* causes peptic ulcer disease (PUD) [1]. *H. pylori* is a causative agent of acute and chronic gastritis and a major predisposing factor for peptic ulcer disease, gastric cancer, and gastric lymphoma [1]. In 2018, *H. pylori* was responsible for 810,000 new cases of non-cardia gastric cancer worldwide [2], and about 8 in 10 cases of gastric cancer are due to *H. pylori* infection [2]. It infects almost half of the world's population and is almost ubiquitous everywhere. More than 80% of PUD is caused by *H. pylori*, and the estimated lifetime risk of PUD in *H. pylori*-infected patients is approximately 15% [3]. Gastric cancer is the third leading cause of cancer-related death worldwide, and *H. pylori* is responsible for 74.7% of all non-cardia gastric cancer [3]. Gastric cancer and PUD together cause 1 million deaths annually [3]. *Helicobacter* 

*pylori* infection is a widespread condition that often remains asymptomatic in 90% of cases. However, this serves to be a major disadvantage as this infection can progress and result in chronic gastritis. *H. pylori* has been identified as one of the main causes of chronic gastritis. The prolonged inflammation caused by *H. pylori* can lead to significant changes in the gastric mucosa such as loss of gland and normal epithelium being replaced by collagen tissue. All this can lead to atrophic gastritis. Moreover, chronic gastritis can lead to intestinal metaplasia, a condition where the gastric epithelial cell undergoes transformation to cells that partially resemble those typically found in the small or large intestine. Both atrophic gastritis and intestinal metaplasia commonly called as chronic atrophic gastritis (CAG) are precancerous conditions, which have the potential to evolve into gastric cancer (GC) [4].

## **2. Prevalence and risk factors**

*H. pylori* is a common bacterial infection that has infected 4.4 billion people worldwide, almost half of the world's population, with varying prevalences of 24–85% in different countries [1]. According to a systematic review, there is wide variation in the prevalence between regions and countries, with the highest prevalence in Africa (79%), Latin America and the Caribbean (65%), and Asia (59%). It is lowest in North America (37%) and Oceania (24.6%) [5]. It is almost ubiquitous in Southeast Asia. The prevalence varies among different countries within the same region, and it varies among different ethnic/racial groups [5]. *H. pylori* infection is chronic, and it is commonly acquired during childhood. The exact means of acquisition is unknown. It is spread from person to person through oral-oral and oral-fecal transmission. Common risk factors include age, lower socioeconomic status, certain race/ethnic groups, poor hygienic conditions such as poor sanitation, lack of access to clean water and water contamination, people with a family history of infection, certain occupations such as sheep herding, healthcare, etc. [1].

### **3. Pathogenesis**

*H. pylori* colonizes the stomach's acidic environment by means of 6–8 sheathed flagella, which enable it to inhabit the gastric mucus layer. Various chemotactic factors and metals are responsible for the mobility of *H. pylori* [1]. It contains intrinsic enzymes that play an important role in colonization. First, an enzyme called urease splits urea into carbon dioxide (CO2) and ammonia, which attenuates the acidity of the stomach environment. Second, the hydrogenase enzyme enables bacteria to use hydrogen as a source of energy. Various adhesion molecules and surface receptors help attach bacteria to gastric epithelial cells [1]. Various virulence factors, such as cytotoxin-associated gene A (Cag A) and non-Cag A factors like vacuolating cytotoxin (Vac A), duodenal ulcer promoting gene A (Dup A), outer inflammatory protein (Oip A), and gamma-glutamyl transpeptidase (GGT), induce changes in the epithelial cells, such as apoptosis, and act as proinflammatory agents [1]. Bacteria with certain virulence factors are more pathogenic than others and cause peptic ulcer disease and gastric cancer. In response to the colonization and attachment of bacteria, host cells initiate an inflammatory response mainly mediated by TH1 cells [1]. Various cytokines and interleukins are released, which are either pro-inflammatory or anti-inflammatory, leading to chronic inflammation [1]. *H. pylori* infection remains

asymptomatic except in some cases where it leads to peptic ulcer, chronic gastritis, atrophic gastritis, and eventually gastric cancer [1, 6].
