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 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
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-7782.155849

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  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 2024 Mar 19];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)

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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.

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

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

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

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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.

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

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

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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

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    Figures

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

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



 

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