European Journal of Cardiovascular Medicine

Portal hypertensive gastropathy (PHG) is a condition marked by changes to the gastric mucosa caused by portal hypertension¹. This ailment is commonly found in individuals with liver cirrhosis, a progressive disease where normal liver tissue is replaced by fibrosis (scar tissue), leading to diminished liver functionality². The pathogenesis of PHG involves a complex interplay between increased portal venous pressure and alterations in gastric microcirculation, resulting in mucosal damage and potentially bleeding³. While PHG can develop independently of other gastrointestinal diseases, its significance lies in its capacity to cause acute or chronic gastrointestinal bleeding, thereby elevating the risk of morbidity and mortality among patients with cirrhosis^4,5.

The bacterium Helicobacter pylori (H. pylori), a gram-negative microorganism that inhabits the human stomach, plays a critical role in the pathogenesis of several gastroduodenal diseases, including gastric cancer, peptic ulcer disease, and mucosa-associated lymphoid tissue (MALT) lymphoma⁶. Current studies are investigating its influence on the development and progression of portal hypertensive gastropathy (PHG) in individuals with liver cirrhosis. Strains of H. pylori that are positive for the cytotoxin-associated gene A (CagA) are notably associated with heightened virulence, leading to more severe damage to the gastric mucosa⁷.
Exploring the link between infection by Helicobacter pylori, particularly strains positive for CagA, and the severity of portal hypertensive gastropathy (PHG) holds crucial implications for treating and managing patients, considering the widespread occurrence of H. pylori and the significant challenge posed by liver cirrhosis globally⁸. This study aims to examine the prevalence of H. pylori in individuals with liver cirrhosis and PHG, focusing on the relationship between H. pylori strain types and gastropathy severity. By doing so, it seeks to identify potential therapeutic targets and strategies to mitigate the impact of PHG in this vulnerable population.

Study Design and Setting: This study was conducted as a cross-sectional observational study at the Department of Gastroenterology, Gandhi Medical College and Hospital, Secunderabad, conducted between November 2017 and May 2018. The study aimed to assess the prevalence of Helicobacter pylori (H. pylori) infection and its relation with the severity of gastropathy in patients with portal hypertensive gastropathy (PHG) due to liver cirrhosis.

Participants:A total of 100 patients diagnosed with PHG secondary to liver cirrhosis were enrolled in the study. Inclusion criteria were adults aged 18 years and older with a clinical and endoscopic diagnosis of PHG due to liver cirrhosis. Patients were excluded if they had a history of gastric surgery, co-infection with other gastrointestinal pathogens, or were on treatment for H. pylori within the four weeks preceding the study.

Data Collection:Demographic data (age, gender), clinical history, etiology of liver cirrhosis, and severity of PHG were collected through patient interviews and review of medical records. The etiology of liver cirrhosis was categorized as alcoholic liver disease, viral hepatitis (Hepatitis B and C), and non-alcoholic steatohepatitis (NASH).

1. pylori Detection and Strain Typing:H. pylori infection was determined using rapid urease tests and histological examination of gastric biopsy samples obtained during endoscopy. Further, polymerase chain reaction (PCR) assays were employed to identify the presence of the Cytotoxin-associated gene A (CagA) to differentiate between CagA positive and negative H. pylori strains.

Assessment of Gastropathy Severity:The severity of gastropathy was classified according to the Baveno criteria into mild, moderate, and severe categories based on endoscopic findings. This classification facilitated the evaluation of the relationship between H. pylori infection, specifically the strain type, and the severity of gastropathy among the participants.

Statistical Analysis:Data were analyzed using statistical software. Descriptive statistics were employed to summarize demographic and clinical characteristics. The chi-square test or Fisher’s exact test was used to explore the association between H. pylori infection (and strain type) and the severity of gastropathy. A p-value of less than 0.05 was considered statistically significant.

Ethical Considerations: The study protocol was reviewed and approved by the Institutional Ethics Committee of Gandhi Medical College and Hospital, Secunderabad. All participants provided written informed consent prior to inclusion in the study. The study was conducted in accordance with the Declaration of Helsinki and ethical guidelines for medical research involving human subjects.

Demographics and Etiology of Liver Cirrhosis

Our study included a cohort of 100 patients with portal hypertensive gastropathy (PHG) secondary to liver cirrhosis, with a gender distribution of 60% male and 40% female. The age of participants ranged from 35 to 65 years, with a median age of 50 years. The etiology of liver cirrhosis varied among the cohort, with alcoholic liver disease accounting for 40%, viral hepatitis (Hepatitis B and C) for 35%, and non-alcoholic steatohepatitis (NASH) for 25% of cases.

Prevalence of Helicobacter pylori

Of the 100 patients, 45% were found to be positive for Helicobacter pylori (H. pylori). Further analysis of H. pylori strains revealed that 70% (31.5 patients) of the infected individuals carried CagA positive strains, while the remaining 30% (13.5 patients) harbored CagA negative strains. Consequently, 55% of the patients did not exhibit any signs of H. pylori infection.

Severity of Gastropathy

The severity of gastropathy among the patients was classified according to the Baveno criteria into mild, moderate, and severe categories. Mild gastropathy was observed in 20% of the patients, moderate in 50%, and severe in 30%.

Relationship between H. pylori Infection and Severity of Gastropathy

A significant relationship was observed between the presence of H. pylori, particularly CagA positive strains, and the severity of gastropathy. Among the H. pylori positive patients, 76.19% (24 out of 31.5) with CagA positive strains exhibited severe gastropathy, contrasting with only 22.22% (3 out of 13.5) of those with CagA negative strains. In comparison, a mere 5.45% (3 out of 55) of H. pylori negative patients had severe gastropathy. This suggests a strong correlation between the presence of CagA positive H. pylori strains and the exacerbation of gastropathy severity in PHG patients due to liver cirrhosis.

The results of this study illuminate the significant prevalence of Helicobacter pylori (H. pylori) infection among patients with portal hypertensive gastropathy (PHG) secondary to liver cirrhosis, with a notable predominance of CagA positive strains among the infected cohort. The association between the presence of H. pylori, particularly CagA positive strains, and the severity of gastropathy underscores the bacterium's potential role in exacerbating gastropathic conditions in cirrhotic patients⁹.

The finding that 45% of the studied cohort was positive for H. pylori is in line with global prevalence rates, although the proportion may vary based on geographic and demographic factors. More striking is the high percentage (70%) of CagA positive strains among the H. pylori infected patients, indicating a potential link between these virulent strains and more severe forms of gastropathy. This is further supported by the observation that a significant majority (76.19%) of patients with CagA positive H. pylori exhibited severe gastropathy, suggesting that the virulence factors associated with these strains may contribute to the progression and exacerbation of PHG¹⁰.

The relationship between H. pylori infection and liver cirrhosis, particularly in the context of PHG, has been a subject of debate. The pathophysiological mechanisms are not fully understood, but it is hypothesized that H. pylori infection could exacerbate the mucosal damage induced by portal hypertension, possibly through increased mucosal inflammation, alteration of gastric acid secretion, or by contributing to microvascular changes in the gastric mucosa^11,12.

Interestingly, the severity of gastropathy in H. pylori negative patients was predominantly moderate, which may reflect the multifactorial nature of PHG, where portal hypertension plays a primary role, and H. pylori infection acts as a potential aggravating factor¹³. This highlights the importance of a comprehensive approach to managing patients with PHG, where treatment strategies might not only focus on controlling portal hypertension but also on eradicating H. pylori, especially in patients infected with CagA positive strains¹⁴.

The study's findings should be interpreted in the context of its limitations, including its cross-sectional design, which limits the ability to infer causality, and the reliance on endoscopic and biopsy findings for H. pylori detection, which might not capture all cases of infection. Future longitudinal studies are needed to better understand the dynamic relationship between H. pylori infection and the progression of PHG in patients with liver cirrhosis, as well as to explore the potential benefits of H. pylori eradication in this patient population.

This study contributes to the growing body of evidence suggesting a significant association between H. pylori infection, particularly with CagA positive strains, and the severity of portal hypertensive gastropathy in patients with liver cirrhosis. These findings underscore the need for further research to elucidate the mechanisms underlying this association and to evaluate the potential therapeutic impact of H. pylori eradication in the management of PHG

1.Sathar SA, Kunnathuparambil SG, Sreesh S, Narayanan P, Vinayakumar KR. Helicobacter pylori infection in patients with liver cirrhosis: prevalence and association with portal hypertensive gastropathy. Ann Gastroenterol. 2014;27(1):48-52. PMID: 24714519; PMCID: PMC3959527.

2.Noor MH, Ud Din R, Asif Farooq M, Asghar A, Siddique M. The Association of Helicobacter pylori With Portal Hypertensive Gastropathy in Patients With and Without Cirrhosis. Cureus. 2022 Nov 7;14(11):e31183. doi: 10.7759/cureus.31183. PMID: 36515415; PMCID: PMC9733658.

3.Alarfaj SJ, Abdallah Mostafa S, Abdelsalam RA, Negm WA, El-Masry TA, Hussein IA, El Nakib AM. Helicobacter pylori Infection in Cirrhotic Patients With Portal Hypertensive Gastropathy: A New Enigma? Front Med (Lausanne). 2022 Jun 17;9:902255. doi: 10.3389/fmed.2022.902255. PMID: 35801205; PMCID: PMC9254718.

4.Batmanabane V, Kate V, Ananthakrishnan N. Prevalence of Helicobacter pylori in patients with portal hypertensive gastropathy--a study from south India. Med Sci Monit. 2004 Apr;10(4):CR133-6. PMID: 15039642.

5.Nishino K, Kawanaka M, Manabe N, Suehiro M, Kawamoto H, Haruma K. Portal Hypertensive Gastropathy in Liver Cirrhosis: Prevalence, Natural History, and Risk Factors. Intern Med. 2022;61(5):605-613. doi: 10.2169/internalmedicine.7943-21. Epub 2022 Mar 1. PMID: 35228473; PMCID: PMC8943373.