• Users Online: 78
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 27  |  Issue : 1  |  Page : 26-31

The role of Helicobacter pylori in minimal hepatic encephalopathy


1 Department of Internal Medicine, Al-Azhar University, Cairo, Egypt
2 Department of Neuropsychiatry, Al-Azhar University, Cairo, Egypt
3 Department of Clinical and Chemical Pathology, National Research Center, Cairo, Egypt

Date of Submission12-May-2014
Date of Acceptance08-Aug-2015
Date of Web Publication27-Apr-2015

Correspondence Address:
Seham S El-seid
Department of Internal Medicine, Al-Azhar University, Cairo
Egypt
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-7782.155849

Rights and Permissions
  Abstract 

Background
One of the causes of death in patients with liver cirrhosis is hepatic encephalopathy (HE). Hyperammonemia is the most important cause of HE.
Aim
The aim of this work was to determine the relation between the Helicobacter pylori infection and minimal hepatic encephalopathy (MHE) in cirrhotic patients and to assess the outcome after treatment of H. pylori.
Patients and methods
This study was carried out on 50 Egyptian cirrhotic patients. The patients were divided into two groups: group A1 (32 positive H. pylori) and group A2 (18 negative H. pylori). Both groups were compared with 20 (age and sex matched) healthy individuals (group B). Patients and controls were subjected to an assessment of history, clinical examination, upper gastrointestinal endoscopy with gastric biopsy for histopathological examination of H. pylori, abdominal ultrasound, neuropsychiatric assessment using the figure connection test (FCT), complete blood count, liver and kidney function tests, and determination of plasma ammonia level. Plasma ammonia level and FCT were measured before and after treatment of H. pylori among patients with positive H. pylori.
Results
Plasma ammonia levels and FCT were highly significantly increased in all cirrhotic patients (group A) compared with the controls (group B) (P < 0.01) and in the positive H. pylori patients (group A1) compared with the negative H. pylori patients (group A2) (P < 0.01) and in group A1 before treatment compared with after treatment (P < 0.01).
Conclusions
There is a highly significant association between H. pylori infection and MHE in cirrhotic patients. The treatment of H. pylori infection reduces the mean plasma ammonia levels and improves FCT results among the infected patients. Therefore, H. pylori infection is an effective treatable risk factor for the clinical management of MHE.

Keywords: Figure connection test, liver cirrhosis, minimal hepatic encephalopathy, plasma ammonia


How to cite this article:
El-seid SS, Attia FA, El-Raouf MA, Abd Al-Azeem GS, Mohammed NA, Anwar H. The role of Helicobacter pylori in minimal hepatic encephalopathy. Egypt J Intern Med 2015;27:26-31

How to cite this URL:
El-seid SS, Attia FA, El-Raouf MA, Abd Al-Azeem GS, Mohammed NA, Anwar H. The role of Helicobacter pylori in minimal hepatic encephalopathy. Egypt J Intern Med [serial online] 2015 [cited 2019 Jul 20];27:26-31. Available from: http://www.esim.eg.net/text.asp?2015/27/1/26/155849


  Introduction Top


Hepatic encephalopathy (HE) has a broad spectrum of neurological symptoms varying from minimal hepatic encephalopathy (MHE) to deep coma and death [1]. Patients with MHE appear clinically well and lack overt encephalopathy; subtle cognitive defects may be present [2]. The diagnosis of MHE is difficult and is made on the basis of neuropsychometric tests [3].

Helicobacter pylori bacteria are rich in urease enzyme producing ammonia from gastric leumen into circulation, causing HE have observed that eradication of H. pylori may reduce the concentration of ammonia in cirrhotic patients [5],[6],[7].

This study was carried out to determine the relation between H. pylori infection and MHE in cirrhotic patients and to assess the outcome after the treatment of H. pylori.


  Patients and methods Top


Study population

The study was carried out on 50 Egyptian patients with liver cirrhosis (group A) and 20 age-matched and sex-matched healthy participants as controls (group B). Patients were recruited from the outpatient clinic and from among the inpatients of the internal medicine department, Al-Zahraa University Hospital, Cairo, Egypt, from January 2013 to June 2013. All patients and controls provided their informed consent before inclusion in the study. Also, approval of ethical committee of faculty of medicine, AL-Azhar University, was obtained. Patients were subdivided into group A1 (positive H. pylori), which included 32 patients, 17 women and 15 men, age range 43-61 years, mean ± SD (53.63 ± 6.89 years), and group A2 (negative H. pylori), which included 18 patients, 11 women and seven men, age range 46-61 years, mean ± SD (50.50 ± 8.8 years). The presence or absence of H. pylori was diagnosed by upper gastrointestinal endoscopy and gastric biopsies for histopathological examination for H. pylori infection. Exclusion criteria: patients with overt HE, hematemesis and melena, a history of H. pylori eradication within the previous 3 months, psychological disorders other than MHE, and severe cardiac, pulmonary, cerebral, and renal disorders were excluded. All patients and controls were subjected to a full assessment of medical history and a thorough clinical examination. Patients with diseases and conditions that increase ammonia level such as overt HE, hematemesis and melena, psychological disorders other than MHE, severe cardiac, pulmonary, cerebral, and renal disorders, and a history of H. pylori eradication within the previous 3 months were excluded. Group A1 was subjected to anti H. pylori treatment in the form of Clarithromycin 500 mg twice daily plus Amoxicillin 1 g twice daily and Pantoprazol 80 mg daily for 2 weeks, followed by Pantoprazol 40 mg daily for the next 2 weeks [8]. We reassessed the effect of anti-H. pylori treatment on hyperammonemia and MHE by determination of plasma ammonia level and figure connection test (FCT).

Laboratory studies

Seven milliliter of fasting venous blood samples were taken from each participant and divided into parts: the first part (1 ml of blood) was placed in a tube containing EDTA for the determination of complete blood count. The second part (1 ml of blood) was placed in a tube containing heparin, the tube was filled completely, and kept tightly closed at all times. It was place immediately on ice and centrifuged, preferably at 4°C, for the determination of ammonia. The third part (3 ml of blood) was left to clot and centrifuged at 1000g for 15 min for routine investigations. The fourth part (1.8 ml of blood) was placed in a tube containing 0.2 ml citrate for the determination of prothrombin time.

Complete blood count was determined using a Coulter counter T890 (Coulter Counter, Harpenden, UK). Prothrombin time and prothrombin concentration (PC) were performed using the standard thromboplastin method. Liver function tests including assessment of serum AST, serum ALT, serum albumin, and serum bilirubin and kidney function tests including determination of blood urea and serum creatinine were carried out on a Hitachi auto analyzer, Hitachi 912 (Roche Diagnostics GmbH, Mannheim, Germany) using colorimetric techniques. Electrolytes including serum sodium and potassium were determined using the ion selective electrode on a Hitachi auto analyzer 912.

Plasma ammonia was determined using the enzymatic ultraviolet method on a Cobas Mira SW (8735) analyzer (Roche Diagnostics Corporation, Indianapolis, Indiana, USA) with glutamate dehydrogenase supplied from Randox Laboratories Ltd (Ardmore, Crumlin Co., Antrim, UK) [9]. Plasma ammonia was determined in all the groups studied and in the patients of group A1 after treatment of H. pylori infection.

Abdominal ultrasonography was performed to assess liver echogenicity, size, surface, any focal lesions, portal vein diameter, hepatic vein, intrahepatic bile radicle, size of spleen, and presence or absence of ascetic fluid.

Upper gastrointestinal endoscopy was performed using Pentax EPKI 5000 endoscopy (Pentax medical EPKI 5000, EG29K, Japan). Gastric biopsies were taken from the stomach of all patients for histopathological examination and detection of H. pylori infection.

Neuropsychiatric assessment was performed using the FCT [10].

We determined FCT in all normal healthy participants and this was considered the standard for FCT represented by minutes (2:35 ± 1:10) and compared it with that of the patients. Then, we determined FCT in group A1 after H. pylori eradication. This test is a derivative of the trail-making test and measures cognitive motor abilities. The test score is the time that a patient needs to perform the test, including the time needed to correct the errors. A low score indicates good performance.

Statistical analysis

Data were analyzed and computed using Microsoft Office 2007 (excel, SPSS Inc., Chicago, Illinois, USA) and statistical package for social science version 16. Parametric data were expressed as mean ± SD and nonparametric data were expressed as number and percentage of the total. Comparison of the mean ± SD of two groups was carried out using a paired and an unpaired Student's t-test. Measurement of the mutual correspondence between two values was performed using the Spearman correlation coefficient. P more than 0.05 was considered nonsignificant, P less than 0.05 was considered significant, and P less than 0.01 was considered highly significant.


  Results Top


The current study enrolled 50 Egyptian cirrhotic patients who were divided into two groups, (group A1) positive H. pylori and (group A2) negative H. pylori, together with 20 apparently healthy individuals as a normal control group (group B).

The demographic, laboratory data, and FCT of the cirrhotic patients studied are shown in [Table 1]. Group A1: positive H. pylori patients: this group included 32 Egyptian cirrhotic patients with positive H. pylori, 17 women (53.2%) and 15 men (46.8%), age range 43-61 years, mean age 53.63 ± 6.89 years. Group A2: negative H. pylori patients: this group included 18 Egyptian H. pylori-negative cirrhotic patients, 11 women (61.2%) and seven men (38.8%), age range 46-61 years, mean age 50.50 ± 8.8 years. Group B: this group included 20 apparently healthy individuals as a normal control group, 10 women (50%) and 10 men (50%), age range 40-62 years, mean age 52.7 ± 4.17 years.
Table 1: Laboratory data and figure connection test of patients in groups A1 and A2 (mean ± SD)

Click here to view


The plasma ammonia level and FCT in all the groups studied are shown in [Table 2] and [Table 3] and [Figure 1] and [Figure 2]. There was a highly significant increase in the plasma ammonia level and FCT in group A1 (positive H. pylori) compared with group A2 (negative H. pylori) (P < 0.01), in group A1 (positive H. pylori) compared with group B (control) (P < 0.01), and in group A1 before treatment compared with group A1 after treatment (P < 0.01).
Figure 1: Plasma ammonia level in group A1 before and after treatment of Helicobacter pylori infection.

Click here to view
Figure 2: Figure connection test (FCT) in group A1 before and after treatment of Helicobacter pylori infection.

Click here to view
Table 2: Plasma ammonia levels in all the groups studied (mean ± SD)

Click here to view
Table 3: Figure connection test in all the groups studied (mean ± SD)

Click here to view


In the positive H. pylori group (group A1), there was a significant positive correlation between ammonia level and the number of colonies of H. pylori in the gastric biopsy and also between FCT and the number of colonies H. pylori (r = 0.761, 0.628, P < 0.01, and P < 0.01), respectively. There was a significant positive correlation between FCT and ammonia (r = 0.928, P < 0.01) [Table 4], [Figure 3] and [Figure 4].
Figure 3: Positive correlation between figure connection test (FCT) and the number of Helicobacter pylori colonies.

Click here to view
Figure 4: Positive correlation between figure connection test (FCT) and plasma ammonia.

Click here to view
Table 4: Correlation between plasma ammonia and figure connection test and number of  Helicobacter pylori Scientific Name Search onies

Click here to view


There was a highly significant increase in the serum ammonia level and FCT in group A1 before treatment in comparison with after treatment of H. pylori infection.


  Discussion Top


The results of the current study showed that there was a statistically highly significant increase in the mean plasma ammonia levels in MHE patients who tested positive for H. pylori infection compared with those with MHE and negative H. pylori infection. This finding is in agreement with the result of Agrawal et al. [11], who showed that ammonia levels were higher in patients with liver cirrhosis who had H. pylori infection in comparison with patients with negative H. pylori.

Agrawal A et al. [4] showed that there was a significant association between H. pylori infection and MHE in patients with liver cirrhosis. Also, another study by Si et al. [12] reported that the ammonia level in the portal vein of cirrhotic patients with H. pylori infection was significantly higher than that in patients without infection. In a study carried out by Jiang et al. [13], a higher blood ammonia level was detected in H. pylori-positive patients with MHE compared with those negative for H. pylori, and this result has been confirmed by Chen et al. [14]. Muzaffar et al. [7] observed that H. pylori eradication reduced the ammonia concentration in cirrhotic patients. However, in several studies, H. pylori infection generated ammonia in the stomach, but the amount appeared to be too small to affect ammonia levels in patients with cirrhosis [15],[16].

The Shanid et al.'s study [17] showed that patients with liver cirrhosis had 35.7% seroprevalence, comparable with the data reported by Batmonabane et al. [18]. A significant association was found between H. pylori infection and portal hypertensive gastropathy (PHG) in cirrhotic patients; also, this infection is correlated to the severity of PHG. PHG provides a favorable environment for the colonization of H. pylori, leading to a high prevalence of this bacterium in cirrhotic patients with PHG. They suggested that edema of the gastric mucosa in cirrhosis might provide a favorable environment for the colonization of H. pylori, especially when there is severe hemorrhagic congestion [17].

Zullo et al. [19] found no significant difference between fasting venous blood ammonia concentrations in patients with H. pylori infection and those without H. pylori infection. This controversy could be explained by the fact that the amount of ammonia produced by H. pylori may depend on the number of bacteria and their distribution in the stomach, gastric pH, and gastric membrane permeability to ammonia, severity of liver impairment, and portal vein branch circulation [14].

Our study showed a highly statistically significant correlation in plasma ammonia level with the severity of H. pylori infection (colonies) and this is in agreement with Chen et al. [14], who observed that H. pylori may increase the blood ammonia concentration and induce HE when the bacterium is widely distributed in the stomach. We found a highly significant reduction in plasma ammonia levels in H. pylori-positive patients with MHE after triple-drug anti-H. pylori treatment. This finding indicates that H. pylori may contribute toward the development of hyperammonemia in patients with liver disease and MHE. This result is in agreement with the result of Agrawal A et al. [4], who showed that anti H. pylori therapy results in a reduction in blood ammonia levels and improvement in MHE, and also in agreement with Schulz et al. [20], who observed that eradication therapy in H. pylori-positive cirrhotic patients may have a beneficial influence on hyperammonemia and MHE.

The results of the present study showed that treatment of H. pylori infection resulted in a reduction in blood ammonia levels and an improvement in MHE, and this in contrast with previous studies that showed no association between eradication of H. pylori infection and improvement in HE [15],[21].

Rekha et al. [22] suggested that H. pylori infection may be a risk factor for HE only in individuals with advanced cirrhosis, but not in early liver disease, and their results do not rule out completely the role of H. pylori infection in the pathogenesis of HE in patients with more advanced liver disease. Therefore, eradication of H. pylori to reduce bacterial ammonia production in the stomach may be effective in patients with hyperammonemia with diffuse H. pylori infection in the stomach.

This current study showed a highly significant increase in the time of FCT in H. pylori-positive groups in comparison with H. pylori-negative groups, and in H. pylori-positive patients before treatment than after treatment. These results are in agreement with the results of Miquel et al. [23] and Shavakhi et al. [24], who reported that FCT showed a significant difference between H. pylori-positive and H. pylori-negative patients and an improvement after eradication of H. pylori. In contrast, Zullo et al. [19] showed that FCT does not improve after eradication of H. pylori.

The study concluded that eradication of H. pylori infection reduces the mean plasma ammonia levels and improves FCT results among the infected patients. Therefore, H. pylori infection is an effective treatable risk factor for the clinical management of MHE. On the basis of our findings, we recommend testing for H. pylori infection in those patients; also, patients with chronic liver disease should be screened for MHE using neuropsychiatric tests for early detection of different cognitive deficits that cannot be detected during a standard neurological examination, but adversely affect daily functioning. We recommended also before giving license of deriving especially the hepatic drivers must be mandatory screened for MHE by neuropsychiatric tests to minimize attacks of road accidents.


  Acknowledgements Top


Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Tianzuo Z, Wolfgang S. The diagnosis and treatment of minimal hepatic encephalopathy. Dtsch Arztebl Int 2012; 109:180-187.  Back to cited text no. 1
    
2.
Prakash R, Mullen KD. Mechanisms, diagnosis and management of hepatic encephalopathy. Nat Rev Gastroenterol Hepatol 2010; 7: 515-525.  Back to cited text no. 2
    
3.
Duarte-Rojo A, Estradas J, Hernández-Ramos R, Ponce-de-León S, Córdoba J, Torre A. Validation of the psychometric hepatic encephalopathy score (PHES) for identifying patients with minimal hepatic encephalopathy. Dig Dis Sci 2011; 56:3014-3023.  Back to cited text no. 3
    
4.
Agrawal A, Gupta A, Chandra M, Koowar S. Role of Helicobacter pylori infection in the pathogenesis of minimal hepatic encephalopathy and effect of its eradication. Indian J Gastroenterol 2011; 30:29-32.  Back to cited text no. 4
    
5.
Perazzo JC, Tallis S, Delfante A, Souto PA, Lemberg A, Eizayaga FX, Romay S Hepatic encephalopathy: an approach to its multiple pathophysiological features. World J Hepatol 2012; 4:50-65.  Back to cited text no. 5
    
6.
Montgomery JY, Bajaj JS. Advances in the evaluation and management of minimal hepatic encephalopathy. Curr Gastroenterol Rep 2011; 13:26-33.  Back to cited text no. 6
    
7.
Muzaffar A, Muhammad R, Akbar Y, Zafrullah, Roohi B, Bhuvnesh Kumar M. Frequency of Helicobacter Pylori among hepatic encephalopathic patients in liver cirrhosis. JLUMHS 2012; 11:93-96.  Back to cited text no. 7
    
8.
De Francesco V, Ierardi E, Hassan C, Zullo A. Helicobacter pylori therapy: present and future. World J Gastrointest Pharmacol Ther 2012; 3:68-73.  Back to cited text no. 8
    
9.
Morgan M, Stubbs M. Hepatic encephalopathy in patients with cirrhosis. Int J Clin Rev 2011; 02:04.  Back to cited text no. 9
    
10.
Weissenborn K. PHES: one label, different goods?! J Hepatol 2008; 49:308-312.  Back to cited text no. 10
    
11.
Agrawal A, Gupta A, Chandra M, Koowar S. Role of Helicobacter pylori infection in the pathogenesis of minimal hepatic encephalopathy and effect of its eradication. Indian J Gastroenterol 2011; 30:29-32.  Back to cited text no. 11
    
12.
Si J, Cao Q, Gao M, Fang L, Qian G, Wang Y. Changes in serum ammonia concentration in cirrhotic patients with Helicobacter pylori infection. Chin Med J (Engl) 2000; 113:1080-1081.  Back to cited text no. 12
    
13.
Jiang HX, Qin SY, Min ZG, Xie MZ, Lin T, Hu BL, Guo XY Association of Helicobacter pylori with elevated blood ammonia levels in cirrhotic patients: a meta-analysis. Yonsei Med J 2013; 54:832-838.  Back to cited text no. 13
    
14.
Chen S, Wang L, Zhu Q, Cai J, Chen T, Si J. Effect of H. pylori infection and its eradication on hyperammonemia and hepatic encephalopathy in cirrhotic patients. World J Gastroenterol 2008; 14:1914-1918.  Back to cited text no. 14
    
15.
Huber M, Rossle M, Siegerstetter V, Ochs A, Haag K, Blum HE, et al. Helicobacter pylori infection does not correlate with plasma ammonia concentration and hepatic encephalopathy in patients with cirrhosis. Hepatogastroenterology 2001; 48:541-544.  Back to cited text no. 15
    
16.
Scotiniotis I, Lucey M, Metz D. Helicobacter pylori infection is not associated with subclinical hepatic encephalopathy in stable cirrhotic patients. Dig Dis Sci 2001; 46:2744-2751.  Back to cited text no. 16
    
17.
Shanid AS, Sojan GK, Srijaya S, Premaletha N, Kattoor RV. H-pylori infection in patients with liver cirrhosis: prevalence and association with PHG. Annals of Gastronterology 2013; 26:1-6.  Back to cited text no. 17
    
18.
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; 10:133-136.  Back to cited text no. 18
    
19.
Zullo A, Hassan C, Morini S. Hepatic encephalopathy and Helicobacter pylori: a critical reappraisal. J Clin Gastroenterol 2003; 37:164-168.  Back to cited text no. 19
    
20.
Schulz C, Schütte K, Malfertheiner P. Does H. pylori eradication therapy benefit patients with hepatic encephalopathy?: systematic review. J Clin Gastroenterol 2014; 48:491-499.  Back to cited text no. 20
    
21.
Kini D, Aggarwal R, Saraswat VA, Naik SR. Role of Helicobacter pylori infection in hyperammonemia and subclinical hepatic encephalopathy in cirrhosis of liver. Indian J Gastroenterol 2001; 20:237-240.  Back to cited text no. 21
    
22.
Rekha C, Phanidhar S, Sagar AV, Revathi A, Asra WA. Role of Helicobacter pylori and hyperammonemia in subclinical hepatic encephalopathy in cirrhosis of liver. Indian J Clin Biochem 2007; 22:136-139.  Back to cited text no. 22
    
23.
Miquel J, Barcena R, Boixeda D, Fernedanz J, SanRoman AL, Martomanz-ArgilaC, Ramosa F Role of Helicobacter pylori infection and its eradication in patients with subclinical hepatic encephalopathy. Eur J Gastroenterol Hepatol 2001; 13:1067-1072.  Back to cited text no. 23
    
24.
Shavakhi A, Shariatifar B, Chuloo S, Minakari M, Sami M. Effect of Helicobacter pylori eradication on hepatic encephalopathy. Hep Mon 2008; 8:121-124.  Back to cited text no. 24
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Patients and methods
Results
Discussion
Acknowledgements
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed1012    
    Printed17    
    Emailed0    
    PDF Downloaded178    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]