role of h. pylori in congestive gastropathy

ROLE OF THE PRESENCE AND TREATMENT OF H. PYLORI AND OTHER TREATMENT MODALITIES ON

THE COURSE OF CONGESTIVE GASTROPATHY

Shindy Mohammed ShendyTropical medicine department, Theodor Bilharz Research Institute

Gastric mucosal lesions that were described with liver cirrhosis and portal hypertension include acute gastric lesions, hemorrhagic gastritis, erosive gastritis or acute gastric erosions (Franco et al., 1977). McCormick and his colleagues postulated congestive gastropathy rather than gastritis in 1985. These lesions were classified into mild gastropathy when mosaic pattern of multiple erythematous areas outlined by a white reticular network or a scarlatina- like pattern of fine pink speckling was detected and severe gastropathy of cherry red spots on a finely granular mucosa (D’Amico et al., 1990). In these studies, the prevalence of mild gastropathy ranged from 20% – to- 94% and of severe gastropathy from 7% – to – 41% in patients with cirrhosis and portal hypertension.

The pathogenesis of PHG is still unclear. Elevated portal pressure can induce changes of local hemodynamics, thus causing congestion in the upper stomach and gastric tissue damage. These changes may then activate cytokines and growth factors, such as tumor necrosis factor alpha, which are substances that activate endothelial constitutive nitric oxide synthase and endothelin 1 in the portal hypertensive gastric mucosa. Overexpressed nitric oxide synthase produces an excess of nitric oxide, which induces hyperdynamic circulation and peroxynitrite overproduction. The overproduction of peroxynitrite, together with endothelin overproduction may cause an increased susceptibility of gastric mucosa to damage. When combined with impaired mucosal defense and healing, these factors may together produce PHG in patients with portal hypertension (Ohta et al., 2002).

Reduced gastric mucosal defense caused by H pylori may account for the pathogenesis of GI lesions in liver cirrhosis. H. pylori is strongly associated with peptic ulcer disease and chronic gastritis, however, several studies showed no relationship between H. pylori infection and congestive gastropathy in liver cirrhosis (Fujiwara et al., 1998).

After oesophageal and fundal varices, portal hypertensive gastropathy (PHG) is the second most frequent cause for bleeding in cirrhotic patients. It accounts for 1 to 8% of primary upper gastrointestinal hemorrhage. Also, it accounts for 30 to 60% of secondary acute or chronic bleeding, mainly after sclerosing therapy of varices. Endoscopy is diagnostic either by showing a typical 'mosaic-pattern' in mild, and a single or confluent 'cherry red spots' in severe forms. Helicobacter pylori or NSAID-induced gastropathy are to be distinguished by biopsies. Secondary prophylaxis with propranolol especially after sclerosing therapy is recommended, primary prophylaxis not (Hermann R, 1997). Evidence in the literature suggests that hypertensive gastropathy might not represent a favorable environment for Helicobacter pylori thus making the diagnostic sensitivity of the biopsy lower than expected (Farinati F et al, 1998).

The aim of this work is to investigate the role and the eradication of H. pylori in the treatment of portal hypertensive gastropathy in comparison with other suggested treatments such as Daflon, sucralfait, propranolol and verapamil. Our intimate aim is to find a simple treatment; if possible; for such common gastro-intestinal disease.

Materials and methods:

This study includes 64 patients who have liver cirrhosis and portal hypertensive gastropathy with or without H. pylori infection. Patients were admitted to Theodor Bilharz Research Institute and were subjected to history taking and clinical examination. Urine, stool, sigmoidoscopy, upper endoscopy and gastric biopsies for histopathology and H. pylori staining before and after treatment were done in all patients. Abdominal ultrasound examination was performed to evaluate the liver disease and its manifestations. CBC, liver function tests, kidney function tests and blood sugar were done routinely in all patients. Most of the patients were diagnosed by previous liver biopsy during the course of their disease. H. pylori serology using ELISA was done in all patients. Patients in this study were divided into the following groups:Group I: included 21 patients with congestive gastropathy and H. pylori infection and were treated

with eradication therapy for H. pylori (PPI, amoxicillin and clarithromythin in the standard doses) followed by PPI for 2 weeks.

Group II: included 20 patients without H. pylori infection and without history of injection sclerotherapy are treated with sucralfait 2gm twice daily and Daflon 500 mg three times daily for three months (Daflon is a purified flavinoid fraction corresponding to diosomin90% and hesperidin flavinoid 10% tablets; Les laboratories, Servier, France).

Group III: 23 patients without H. pylori infection and with history of injection sclerotherapy are treated with propranolol 40 mg three times daily and verapamil 80 mg three times daily for three months.

Statistical AnalysisStatistical analysis was performed using the SPSS 12 for window statistical Package Results are

expressed as absolute values and mean ± SD. Statistical analysis of the data was carried out using the ANOVA test. For correlation studies, the Pearson correlation coefficient was used. A p -value of < 0.05 was considered significant.

RESULTS:Table 1: Some clinical features of patients in the three groups:

Group No. of patients AgeSex H pylori positivity Bleeding status

Male Female Serology biopsy present absent

Group I 21 48.9±13.6 13 8 21 21 0 21

Group II 20 44.85±12.8 11 9 2 0 0 20

Group III 23 44.86±14.5 14 9 5 0 23 0

Table 2: Symptomatic improvement of dyspeptic symptoms in all groups:

GroupNumber of patients sufferingfrom dyspeptic manifestations

No improvement

Mild improvement

Marked improvement

Group I 20/21 0 5 15Group II 14/20 4 7 3Group III 17/23 3 8 6

Effect of therapy on OV and PHG in the three groups (Tables 3, 4 & 5): Table 3: Oesophageal varices and portal hypertensive gastropathy in patients with H pylori infection

(group I):OV PHG PHG, in biopsy

Grade Before ttt After ttt Degree Before ttt After ttt Degree Before ttt After tttGrade I : 5 5 Absent 00 3 Absent 0 6Grade II : 6 6 Mild 10 15 Mild 10 11Grade III: 9 10 Severe 11 3 Severe 11 4Grade IV : 1 0Signif: P=0.7 NS P= 0.001 sign. P=0.000 sig

Table 4: Oesophageal varices and portal hypertensive gastropathy in patients treated with Daflon and sucralfait (group II):

OV PHG PHG, in biopsyGrade Before ttt After ttt Degree Before ttt After ttt Degree Before ttt After ttt

Grade I : 6 6 Absent 0 6 Absent 0 6Grade II : 8 8 Mild 8 14 Mild 8 13Grade III: 4 4 Severe 13 1 Severe 13 2Grade IV : 2 2Signif: P=0.8 NS. P= 0.005 : sig. P=0.001 : sig

Table 5: Oesophageal varices and portal hypertensive gastropathy in patients with history of injection sclerotherapy, treated with propranolol and verapamil (group III):

OV PHG PHG, in biopsyGrade Before ttt After ttt Degree Before ttt After ttt Degree Before ttt After ttt

Grade 0: 15 14Absent 0 5 Absent 0 6

Grade I : 6 7Grade II : 2 2 Mild 8 17 Mild 8 16Grade III: 0 0 Severe 15 1 Severe 15 1Grade IV : 0 0

Signif: P= 0.6 NS P= 0.006 : Sig P= 0.003 : Sig

Comparison of the response of oesophageal varices, and gastropathy to therapy between the three groups using Levene's Test for Equality of Variances for independent samples test found that only oesophageal varices improved significantly in group I in comparison to group II. No differences in the response of PHG in the three groups.

Oesophageal varices were found the only predictive variable among all studied variables for the presence and severity of PHG.

Most of these patients are suffering from dyspeptic symptoms in the form of epigastric discomfort and pain after meals, flatulence and distension. This was more marked in patients with H pylori infection. There is substantial improvement after treatment in all patients that was most marked in patients of group I after eradication of H pylori.

DiscussionIn this study, portal hypertensive gastropathy (PHG) and H pylori infection were found a common

asssociation in Egyptian patients with liver cirrhosis. H pylori infection may be another factor that helps in the development of PHG. This is proved in this study by the significant improvement in such condition after eradication therapy. Such improvement was noticed mainly in the severe cases which become mild after treatment in group I. However, there is no significant change in the mild cases of gastropathy. Thus, H pylori may only add to the severity of the condition but not the initiative factor. Increased expression of inducible nitric oxide synthase (iNOS) has been reported in gastric mucosa of patients with Helicobacter pylori infection or portal hypertensive gastropathy (PHG) but probably there is no additive or synergistic impact between H. pylori and PHG on iNOS expression. Furthermore, It was found that expression of iNOS was significantly higher in patients with severe PHG than in those with mild PHG and without PHG (Arafa UA et al; 2003).

Sucralfait and the venotonic medication; Daflon; also produced significant improvement in PHG, even in mild cases. Sucralfait being a cytoprotective agent to the gastric mucosa added to daflon produced such effect in these patients despite no effect on the large vessels; esophageal varices. These simple and safe medications can be added to the management of these patients particularly those with dyspeptic symptoms from PHG.

After injection sclerotherapy and band ligation, the development of PHG increases (Primignant M et al 2000 and Dong L et al 2003). The use of propranolol and calcium channel blocker; verapamil as secondary prophylaxis for both esophageal varices and PHG seems effective. In this study they produced significant improvement in PHG with changing of most severe cases to mild and complete disappearance of 6 mild lesions. In spite of this marked improved; some cases still have milder grades of varices on treatment (recurrent or not completely eradicated by previous endoscopic therapy).

In this study, esophageal varices were found the only predictive variable for the presence and severity of PHG. This finding is similar to the finding of Dong L. et al. (2003) who found that gastroesophageal varicosity was closely related to PHG, but their degrees are not related.

In some studies, H. pylori was found less frequently in congestive gastropathy patients than in the control group and presence and severity of congestive gastropathy is independent of the H. pylori status (Dai L and Wu X; 1999, Dong L et al 2003, and Batmanabane et al 2004). These researchers suggested that there might be no need for its routine eradication in patients with PHG and it was concluded that portal hypertensive gastropathy does not provide a favorable environment for the colonization of H. pylori.

The prevalence of gastropathy in different studies (and this study) was correlated with the duration of disease, presence and size of esophagogastric varices, and a previous history of endoscopic variceal sclerotherapy (Primignant M et al 2000).

In this study, there is substantial improvement in all patients that was most marked in patients having additional H pylori infection (group I), after eradication therapy. Thus, gastritis due to H pylori adds more loads on the symptomatology of these patients and it is advised to eradicate this infection in patients with cirrhosis.

It is concluded from this study that H pylori may aggravate this disease process and its eradication may be beneficial in patients with liver cirrhosis and portal hypertension. Also, other treatment modalities were effective in decreasing the severity of this disease, which means that this disease process may be aggravated by other factors than H pylori i.e. multifactorial. Such treatment can be

used in combination with or after eradication therapy. More prolonged studies are recommended to prove that such effect is long lasting and is not due to other factors.

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role of h. pylori in congestive gastropathy

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