Al-Azhar Assiut Medical Journal

ORIGINAL ARTICLE
Year
: 2016  |  Volume : 14  |  Issue : 3  |  Page : 109--114

Prevalence of Helicobacter pylori infection in patients with portal hypertensive gastropathy owing to liver cirrhosis in Upper Egypt


Khaled Abd-Alazeim Eid, Muhammad Abd El-Gawad Shawky, Amro Metwaly Hassan, Ahmed Qasem Mohammed, Mostafa Ismail Mohammed 
 Department of Tropical Medicine, Faculty of Medicine, Al-Azhar University, Assiut, Egypt

Correspondence Address:
Muhammad Abd El-Gawad Shawky
Postal code 71524, Assiut
Egypt

Abstract

Background Gastrointestinal bleeding and anemia in patients with liver cirrhosis are common problems caused by various etiologies such as bleeding esophageal and gastric varices, bleeding peptic ulcer whether Helicobacter pylori or non-H. pylori related, portal hypertensive gastropathy (PHG), and other causes. Impairment of the gastric protective barriers and production of inflammatory cytokines such as tumor necrosis factor-α and interleukins, which occur because of colonization of gastric mucosa by H. pylori, may make the stomach more susceptible to the effects of portal hypertension. Aim of work The aim of this study was to investigate the prevalence of H. pylori infection and its association with PHG in patients with liver cirrhosis. Patients and methods Overall, 50 patients with liver cirrhosis and PHG (cases) and 50 patients with cirrhosis without PHG (controls) were enrolled in this study. H. pylori stool antigen rapid bedside test and upper endoscopy were done for patients in both groups to diagnose PHG and H. pylori infection. Results The prevalence of H. pylori infection among patients with PHG was higher than those without PHG (34 vs. 10%, respectively; P=0.031), and prevalence of H. pylori infection was 22% among the whole of the studied groups. There was no correlation between H. pylori infection and severity of PHG (P=0.381), Child score, Model for End-Stage Liver Disease score, or serum albumin level. However, our study showed a significant correlation between splenic size and portal vein diameter in patients with cirrhosis and PHG (P=0.002). Conclusion There is significant association between H. pylori infection and PHG, but there is no significant correlation between H. pylori infection and the severity of PHG or the severity of liver cirrhosis. Also, there is significant correlation between splenic size and portal vein diameter in patients with cirrhosis and PHG.



How to cite this article:
Eid KA, Shawky MA, Hassan AM, Mohammed AQ, Mohammed MI. Prevalence of Helicobacter pylori infection in patients with portal hypertensive gastropathy owing to liver cirrhosis in Upper Egypt.Al-Azhar Assiut Med J 2016;14:109-114


How to cite this URL:
Eid KA, Shawky MA, Hassan AM, Mohammed AQ, Mohammed MI. Prevalence of Helicobacter pylori infection in patients with portal hypertensive gastropathy owing to liver cirrhosis in Upper Egypt. Al-Azhar Assiut Med J [serial online] 2016 [cited 2017 Jun 24 ];14:109-114
Available from: http://www.azmj.eg.net/text.asp?2016/14/3/109/200147


Full Text

 Introduction



Gastrointestinal bleeding is a major cause of hospital admission, morbidity, and mortality in patients with liver cirrhosis. It is caused by various etiologies such as portal hypertension related as bleeding gastroesophageal varices, bleeding portal hypertensive gastropathy (PHG), portal hypertension-related intestinal and colonic lesions, and non-portal hypertension-related causes such as bleeding peptic ulcer either Helicobacter pylori related or not [1].

PHG is characterized by gastric epithelial changes with minimal inflammation and occurs in patients with liver cirrhosis with portal hypertension or those with noncirrhotic portal hypertension. The prevalence of PHG in patients with portal hypertension has been reported to vary between 20 and 80% [2],[3], and the incidence of acute upper gastrointestinal tract bleeding from PHG varies widely (2–12%) [4]. PHG which may be presented by hematemesis, melena, and hematochezia may lead to anemia owing to either overt gastrointestinal bleeding or from occult blood loss [5]. PHG is diagnosed endoscopically as a wide range of mucosal changes such as mucosal edema, flat red spots, angiodysplasia-like lesions, pigmented black-brown spots, mucosal granularity, and reticulated mosaic-like pattern mucosa [6],[7].

H. pylori is frequently encountered in patients with liver cirrhosis [8]. It plays an important role in peptic ulcer development in patients with cirrhosis [9]. However, the effect of H. pylori on liver cirrhosis and PHG is still matter of controversy [10],[11]. Therefore, we evaluated the prevalence of H. pylori infection and its association with PHG in patients with liver cirrhosis in Upper Egypt.

H. pylori antigen is a protein component in the structure of the H. pylori bacilli and is shed in the stool of infected persons. H. pylori antigen has been approved by the Food and Drug Administration for the diagnosis of H. pylori infection and assessment of response to treatment, with the same applications as urea breath test. Serology result should not be used because it detects antibodies that persist after eradication of infection [12].

 Patients and methods



The study was a prospective case–control study conducted on patients with liver cirrhosis admitted to Tropical Medicine Department, Al-Azhar University, Assiut, from January 2015 to July 2015 after the approval from the ethical committee of Faculty of Medicine, Al-Azhar University, Assiut. An informed consent was obtained from each patient.

A total of 100 patients were enrolled in the study: 50 patients with liver cirrhosis and PHG as cases and 50 patients with liver cirrhosis but without PHG as a control group, who were age and sex matched with cases. Patients with active peptic ulcer disease, primary or secondary malignancy, past gastric surgery, recent injection sclerotherapy or band ligation for esophageal or gastric varices within 4 weeks, patients on NSAIDs or proton pump inhibitors, and those who underwent eradication therapy for H. pylori in the past 2 months were excluded from our study.

For all patients admitted to the hospital, detailed history taking, thorough clinical examination, routine laboratory investigations, and abdominal ultrasound (Esaote ID; CE0051, Genoa, Italy with a 4.5 MHz convex probe) were done. The diagnosis of liver cirrhosis was based on clinical, biochemical, and radiological findings. The detection of hepatitis C virus (HCV) antibodies, hepatitis B virus surface antigen, and Bilharzia antibody was done in all patients. Upper gastrointestinal tract endoscopy was performed for all patients (Pentax videoscope; Pentax EG-2990K Video Gastroscope, Japan) to verify the presence of PHG, assess its severity, and assess the presence of esophageal varices (EV) or fundal varices. Baveno classification was used to assess the severity of PHG. PHG scoring system proposed by Baveno III consensus workshop ([Table 1]) was used to assess PHG [13].{Table 1}

H. pylori infection was assessed by Atlas H. pylori antigen test (Atlas Medical, William James House, Cowley Road, Cambridge, CB4 0WX, UK) on the same day of endoscopic examination. Atlas H. pylori antigen test (Atlas Medical) is a rapid immunoassay using a monoclonal anti-H. pylori antibody on a strip for the detection of H. pylori infections in stool specimens. The H. pylori antigen reacts with the conjugate-pink red latex particles sensibilized with anti-H. pylori monoclonal antibody coated to the membrane of the strip. The formed H. pylori-conjugate complex, which migrates upward on the membrane by capillary action, binds to the specific antibody molecules fixed to the reaction zone. The test was performed according to the manufacturer’s recommendations.

The severity of liver disease was assessed using Child–Pugh classification ([Table 2]) and Model for End-Stage Liver Disease (MELD). The MELD score is calculated as follows: MELD score=10×[0.957×ln(creatinine)]+[0.378×ln(bilirubin)]+[1.12×ln(INR)]+6.43. It was calculated by an online calculator of the United Network for Organ Sharing (http://www.unos.org).{Table 2}

Statistical analysis was done using IBM-SPSS (Armonk, NY: IBM Corp) 22 for Windows 10 operating system. Categorical data parameters were presented in the form of frequency and percentage. Comparison was performed by χ2-test for categorical data. Quantitative data were expressed in the form of mean±SD. Comparison between groups was performed by using independent t-sample test. Analyses of variance test was used to check the significance between groups for quantitative data. Spearman’s correlation coefficient was used to get the correlation among parameters. Probability level (P) was assumed significant if it was less than 0.05.

 Results



A total of 100 patients with liver cirrhosis were enrolled in the study: 50 patients with cirrhosis with endoscopic diagnosis of PHG as cases and 50 patients with cirrhosis without PHG as a control group.

The mean age of cases group was 54.06±11.88 years and 66% were men, whereas the mean age of the control was 55.20±11.79 years and 50% were men.

The baseline characteristics of the two studied groups are listed in [Table 3].{Table 3}

The study showed no significant differences between cases and controls regarding age, sex, and presence of ascites. In the cases group, 15 (30%) patients were classified as Child class A, 32 (64%) as Child class B, and three (6%) as Child class C versus 27 (54%), 20 (40%) and three (6%) patients were Child class A, Child class B, and Child class C, respectively, in the control group, with no significant differences between cases and controls. No statistically significant differences were found between cases and control for the following laboratory data: fasting blood sugar, aspartate aminotransferase, alanine aminotransferase, bilirubin level, albumin level, international normalized ratio, creatinine level, white blood cells, hemoglobin level, platelets level, Child score, and MELD score ([Table 3]).

[Table 4] shows the etiology of cirrhosis among the studied groups. Hepatitis C was found in 75% of patients followed by hepatitis B in 18%, whereas other causes of cirrhosis were 7%.{Table 4}

There is a significant correlation between H. pylori infection and PHG. Results showed that H. pylori infection was more prevalent among cases (34%) than control (10%) (P=0.036) ([Figure 1] and [Table 5]).{Figure 1}{Table 5}

However, no significant correlation was found between H. pylori infection and severity of PHG (P=0.079) ([Table 6]).{Table 6}

There was a significant correlation between splenic diameter and portal vein (PV) diameter and PHG with P equal to 0.002 ([Table 7]).{Table 7}

Endoscopic examination of cases showed that 13 (26%) had grade I EV, 28 (56%) had grade II EV, seven (14%) had grade III EV, and two (4%) had grade IV EV, and endoscopic examination of controls showed that 18 (36%) had grade I EV, 26 (52%) had grade II EV, five (10%) had grade III EV, and one (2%) had grade IV EV. The study showed that there is no significant correlation between grade of EV and PHG (P=0.635) ([Table 8]).{Table 8}

 Discussion



PHG is not the most common cause of significant upper gastrointestinal tract bleeding in patients with portal hypertension, but bleeding is the most important complication of this disease. The incidence of acute upper gastrointestinal tract bleeding from PHG varies widely (2–12%) [4]. It is reported that ∼10% of PHGs cause anemia because of the chronic blood loss, and 2.5% of patients experienced acute bleeding [14].

The pathogenesis of PHG is likely to be complicated, but PHG seems to occur because of portal hypertension and alteration in gastric microcirculation, which produce mucosal surface hypoxia [15],[16] and affect epithelial cell integrity, probably mediated through local factors such as overproduction of nitric oxide, oxygen free radicals, endothelin-1, tumor necrosis factor-α, and prostaglandins [17].

However, there are other factors associated with the presence and severity of PHG. These include prior treatment of EV, etiology of portal hypertension (cirrhotic vs. noncirrhotic), severity of primary liver disease, and H. pylori infection [18].

Colonization of the gastric mucosa by H. pylori might have an indirect role in PHG as colonization is, at least theoretically, associated with inflammation. H. pylori virulence factors induce the production of proinflammatory cytokines such as tumor necrosis factor-α, which enhance mucosal inflammation [19].

This study showed no statistically significant difference between cases and control regarding age and sex because the sample was cross-matched (P=0.559 and 0.279, respectively). Also, this study showed no statistically significant association between PHG and fasting blood sugar, aspartate aminotransferase, alanine aminotransferase, bilirubin, albumin, international normalized ratio, creatinine, white blood cells, red blood cells, and platelets.

Our study showed no significant difference between cases and control regarding Child score with mean score for cases being 6.96±1.24 and for control being 6.60±1.50 (P=0.423). This agrees with the studies by Safwat et al. [20] and Abbas et al. [21] (P=0.59 and 0.735, respectively). In contrast, Kim et al. [22] showed that there is significant association between PHG and Child score.

The study also showed no statistically significant association between PHG and MELD score, with mean score for cases being 17.4±3.22 and for control being 16.7±1.94 (P=0.396). This agrees with the studies by Safwat et al. [20] and Abbas et al. [21] (P=0.468 and 0.921, respectively). This is in contrast to the study by El-Masry et al. [23], who revealed that the prevalence of H. pylori infection in HCV-infected patients was increased very significantly with increasing MELD score (P=0.003).

This study showed high prevalence of HCV infection (75%) among patients followed by hepatitis B (18%) and other causes of cirrhosis (7%).

This study showed significant difference between cases and control in the prevalence of H. pylori infection (34 vs. 10%) (P=0.036). This agrees with the studies by Safwat et al. [20] and Sathar et al. [24]. In contrast, Hammad et al. [25] showed that the H. pylori infection did not correlate with PHG, and there was statistically insignificant difference between the prevalence of H. pylori infection in patients with PHG (70%) and control group (63.3%) (P=0.523).

However, the prevalence of H. pylori infection in our study was less than what was expected to be in our country, as a developing country, which may reach up to 80% of the population [26]. However, the prevalence of H. pylori infection may differ in regions of the same country, owing to differences in the socioeconomic levels, educational levels, hygienic measures, and environmental sanitations [27]. This low prevalence also may be because of the use of stool antigen test in screening for H. pylori, which only diagnose those with current infection, rather than tests depending on immunoglobulin G antibodies, which do not differentiate between old and current infections, giving rise to high prevalence rates. Also the excess use of antibiotics and proton pump inhibitors in patients with liver cirrhosis may also help to eradicate H. pylori bacilli in some patients.

Our study also showed no statistically significant correlation between H. pylori infection and severity of PHG (P=0.079). This agrees with Pan et al. [18] and Abbas et al. [21] who showed no significant association between H. pylori infection and severity of PHG in patients with cirrhosis (P=0.332 and 0.749, respectively). In contrast, Safawat et al. [20] and Hammad et al. [25] showed significant relation between H. pylori infection and severity of PHG (P=0.041 and 0.002, respectively).

Our study showed significant differences between cases and control regarding splenic size and PV diameter, with average PV diameter of cases being 13.31±1.537 mm and of control being 11.88±0.885 mm (P=0.002). This agrees with Abbas et al. [21] who showed that the average splenic size of patients without PHG was 12.5±2.5 cm and those with PHG was 15.1±3.1 cm (P=0.000). On the contrary, Abbas and colleagues showed no significant association between PHG and PV diameter, with average PV diameter of patients without PHG being 10.3±2.4 mm and of patients with PHG being 11.0±2.3 mm (P=0.091).

This study showed no statistically significant correlation between PHG and degree of EV (P=0.635). This agrees with the study by Safwat et al. [20] (P=0.961). In contrast, Abbas et al. [21] and Pan et al. [18] showed significant association between cases and control regarding grade of EV (P=0.000 and 0.001, respectively).

 Conclusion



There is significant association between H. pylori infection and PHG, but there is no significant correlation between H. pylori infection and the severity of PHG or the severity of liver cirrhosis. Also there is significant correlation between splenic size and PV diameter in patients with cirrhosis and PHG.

Study limitations

Given the small sample size, we recommend a second study involving more patients.

Acknowledgements

The authors thank Professor Hamdy Mahfouz Moustafa, Head of Gastroenterology and Hepatology Department, Faculty of Medicine, Al-Azhar University, Assiut, Egypt.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Holland-Bill L. Chronic liver disease and 90-day mortality in 21 359 patients following peptic ulcer bleeding − a Nationwide Cohort Study. Aliment Pharmacol Ther 2015; 41:564–572.
2Sarin SK. The natural history of portal hypertensive gastropathy: influence of variceal eradication. Am J Gastroenterol 2000; 95:2888–2893.
3Primignani M. Natural history of portal hypertensive gastropathy in patients with liver cirrhosis. The New Italian Endoscopic Club for the study and treatment of esophageal varices (NIEC). Gastroenterology 2000; 119:181–187.
4Merli M. The natural history of portal hypertensive gastropathy in patients with liver cirrhosis and mild portal hypertension. Am J Gastroenterol 2004; 99:1959–1965.
5Thuluvath PJ, Yoo HY. Portal hypertensive gastropathy. Am J Gastroenterol 2002; 97:2973–2978.
6Papazian A. Portal hypertensive gastric-mucosa − an endoscopic study. Gut 1986; 27:1199–1203.
7Cales P. Gastroesophageal endoscopic features in cirrhosis. Observer variability, interassociations, and relationship to hepatic dysfunction. Gastroenterology 1990; 98:156–162.
8Dore MP. Active peptic ulcer disease in patients with hepatitis C virus-related cirrhosis: the role of Helicobacter pylori infection and portal hypertensive gastropathy. Can J Gastroenterol 2004; 18:521–524.
9Vergara M, Calvet X, Roque M. Helicobacter pylori is a risk factor for peptic ulcer disease in cirrhotic patients. A meta-analysis. Eur J Gastroenterol Hepatol 2002; 14:717–722.
10Al Mofleh IA. Does Helicobacter pylori affect portal hypertensive gastropathy? Saudi J Gastroenterol 2007; 13:95–97.
11Urso G. Role of Helicobacter pylori in patients with portal hypertensive gastropathy by liver cirrhosis hepatitis C virus-related. Minerva Gastroenterol Dietol 2006; 52:303–308.
12Ong SP, Duggan A. Eradication of Helicobacter pylori in clinical situations. Clin Exp Med 2004; 4:30–38.
13De Franchis R. Updating consensus in portal hypertension: report of the Baveno III Consensus Workshop on definitions, methodology and therapeutic strategies in portal hypertension. J Hepatol 2000; 33:846–852.
14Chung WJ. Management of portal hypertensive gastropathy and other bleeding. Clin Mol Hepatol 2014; 20:1–5.
15Fontana RJ. Portal hypertensive gastropathy in chronic hepatitis C patients with bridging fibrosis and compensated cirrhosis: results from the HALT-C trial. Am J Gastroenterol 2006; 101:983–992.
16Tarnawski AS. Microvascular abnormalities of the portal hypertensive gastric mucosa. Hepatology 1988; 8:1488–1494.
17Kawanaka H. Defective mitogen-activated protein kinase (ERK2) signaling in gastric mucosa of portal hypertensive rats: potential therapeutic implications. Hepatology 2001; 34:990–999.
18Pan WD, Xun RY, Chen YM. Correlations of portal hypertensive gastropathy of hepatitis B cirrhosis with other factors. Hepatobiliary Pancreat Dis Int 2002; 1:527–531.
19Patel MK, Trombly MI, Kurt-Jones EA. Innate immune responses to Helicobacter pylori infection: an overview. Methods Mol Biol 2012; 921:205–207.
20Safwat E, Hussein HA, Hakim SA. Helicobacter pylori in Egyptian patients with HCV- related liver cirrhosis and portal hypertensive gastropathy: prevalence and relation to disease severity. Life Sci J 2015; 12:168–173.
21Abbas Z. Effect of Helicobacter pylori and its virulence factors on portal hypertensive gastropathy and interleukin (IL)-8, IL-10, and tumor necrosis factor-alpha levels. Saudi J Gastroenterol 2014; 20:120–127.
22Kim DJ. Helicobacter pylori infection and peptic ulcer disease in patients with liver cirrhosis. Korean J Intern Med 2008; 23:16–21.
23El-Masry S. Helicobacter pylori and hepatitis C virus coinfection in Egyptian patients. J Glob Infect Dis 2010; 2:4–9.
24Sathar SA. Infection in patients with liver cirrhosis: prevalence and association with portal hypertensive gastropathy. Ann Gastroenterol 2014; 27:48–52.
25Hammad OM. Correlation of portal hypertensive gastropathy with Helicobacter Pylori infection, liver dysfunction, hypersplenism and oesophageal varices. Medical J Cairo Univ 2009; 77:597–601.
26Wu MS. A case-control study of association of Helicobacter pylori infection with morbid obesity in Taiwan. Arch Intern Med 2005; 165:1552–1555.
27Hunt RH. Helicobacter pylori in developing countries. World Gastroenterology Organisation Global Guideline. J Gastrointestin Liver Dis 2011; 20:299–304.