1 Transplantation and Liver Surgery, Helsinki University Hospital, 2 Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki and Helsinki University Hospital Diagnostics and 3 Department of Internal Medicine, Division of Nephrology, Helsinki University Hospital, Helsinki, Finland
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Abstract |
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Methods. Between 1991 and 1994, serum H. pylori antibodies were determined in samples taken just before transplantation from 500 consecutive recipients of kidney transplants. Clinical data were collected retrospectively by means of questionnaires sent to the patients and from the national kidney transplantation registry.
Results. The prevalence of seropositivity of H. pylori was 31% in the 500 renal transplant subjects, and the seropositivity increased with age. There were no differences in patient or graft survival between the seronegative and seropositive patients. During the first 3 months after transplantation, five seronegative and one seropositive patient had gastroduodenal ulcers, with bleeding complications in three of the seronegative ones. After 3 months, there were more ulcers in the seropositive group (6 vs 3%) and more oesophagitis in the seronegative group (9 vs 7%). During the 6-year follow-up, two cases of gastroduodenal malignancies were found in the helicobacter-positive group and none in the seronegative group.
Conclusions. Helicobacter pylori infections did not result in significant postoperative gastric complications. Two of the 155 seropositive patients developed gastroduodenal malignancies.
Keywords: Helicobacter pylori; kidney transplantation; malignancy; ulcer
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Introduction |
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The recognition of Helicobacter pylori has largely changed the understanding of the aetiology of peptic ulcer disease. Nowadays, H. pylori is accepted as a major aetiologic factor in gastritis and gastro-duodenal ulceration [2]. Epidemiological studies have demonstrated, moreover, an association between H. pylori and gastric cancer, and in 1994 H. pylori was classified as a group I carcinogen by the International Agency for Research on Cancer [3].
The aim of this study was to determine the presence of H. pylori in a group of recipients of kidney transplants and to evaluate the correlation of upper gastrointestinal complications and dyspeptic symptoms with H. pylori infection in these patients after kidney transplantation. We also wanted to determine if H. pylori infection had any influence on graft or patient survival.
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Subjects and methods |
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Gastrointestinal complications
All living recipients were sent a questionnaire, in which they were asked to write down any upper gastrointestinal complaints they had after kidney transplantation as well as the results of examinations and the treatments they had for those complaints. Data from medical records, with a special interest on macroscopic and microscopic findings of the oesophago-gastro-duodenoscopies performed, were requested (with patients written consent) from all hospitals reported by the patient. In the case of deceased patients and of those who did not return their questionnaires, the data was collected from follow-up information sent regularly to the national kidney transplantation registry by the nephrologists responsible for the follow-up of these patients.
Serum analysis
Serum samples were obtained just before kidney transplantation from all the recipients, and were kept frozen at -20°C before analysis. IgG and IgA antibodies for H. pylori were measured by an in-house enzyme immunoassay. The antigen used was an acid glycine extract from H. pylori NCTC 11637. The absorbance readings were converted to reciprocals of the end point titres. Seven hundred was considered positive for IgG and 70 for IgA. The sensitivity and specificity of this test have been shown to be 99 and 97% for IgG and 61 and 99% for IgA [4].
Ethics
The study was approved by the Ethics Committee of Surgical Hospital, Helsinki University Hospital.
Statistics
Pearson's 2 and MannWhitney U-test were used to compare groups of patients. Patient and graft survival was evaluated using the life table method.
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Results |
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Gastroduodenal complications
Gastroduodenal complications in the first 3 months
oesophago-gastro-duodenoscopy was performed on 17 (3.4%) patients who had gastrointestinal complaints during the first 3 postoperative months after kidney transplantation (Table 3). Gastroduodenal ulcer was diagnosed by endoscopy in five seronegative and one seropositive patients during the first 3 months (Table 4
). All of these patients were treated successfully. Five of the six patients with postoperative ulcers received low-dose ASA prophylaxis. In four of the six ulcer patients the ulcer developed after rejection therapy, and furthermore, one of these patients was diagnosed simultaneously to have a cytomegalovirus (CMV) viraemia (Table 4
).
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Gastroduodenal complications in the follow-up
During follow-up, oesophago-gastro-duodenoscopy was performed on 92 patients (35 seropositive). The findings are presented in Table 3. None of the seronegative patients turned out to have H. pylori in the biopsies. There were more ulcers in the seropositive patient group (6 vs 3%), but oesophagitis was more common in the seronegative group (9 vs 7%).
Overall, nine of the 25 ulcer patients (three seropositive) had an acute rejection during the first 3 months. Helicobacter pylori infection was histologically verified in 24 seropositive patients of whom 16 got eradication therapy. During follow-up, 28 (18%) of the H. pylori-positive patients and 59 (17%) of the seronegative patients used proton pump inhibitors or H2 blockers for a period of 6 months. This was done partly because of their former histories of gastroduodenal ulcers and partly because of their dyspeptic complaints.
In the seropositive group there was one ulcer perforation, one year after the transplantation which required laparotomy and ulcer ligation. In both patient groups, one patient underwent fundoplication due to severe reflux oesophagitis after transplantation.
Gastroduodenal malignancies
In the seropositive patient group two patients developed gastroduodenal malignancies. One female patient developed a gastric carcinoma 5 years after transplantation, at the age of 70 and a 64-year-old male was diagnosed to have a carcinoid tumour in the duodenal bulb 3 years after the transplantation. Both patients were treated surgically. In addition, one seropositive patient developed a carcinoma of the hypopharynx, which infiltrated the oesophagus and was diagnosed in oesophago-gastro-duodenoscopy 6 years after the transplantation. No upper gastrointestinal malignancies were found in the seronegative patient group.
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Discussion |
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The number of new H. pylori infections has been shown to be decreasing in developed countries, and consequently, the prevalence of the infection is higher in older age groups [7,8]. In the present series, H. pylori seropositivity was 31%, but the median age of seropositive subjects was significantly higher compared to the seronegative ones. These figures do not differ from another series, which described the age-dependent incidence of H. pylori infection in the general Finnish population [9]. A similar prevalence has also been shown by other authors in renal transplant patients [1012].
Upper gastrointestinal problems were common in kidney transplantation patients before the appearance of modern ulcer medications. In one report from the 1970s, 29% had gastroduodenal complications, of which the biggest group consisted of gastroduodenal haemorrhage. The mortality secondary to upper gastrointestinal haemorrhage was 29% in that study [13]. In a more recent study from the 1990s, the rate of the total gastrointestinal complications was 16%, 9.6% being gastroduodenal complications. In this study the mortality as a result of gastrointestinal complications was about 1% [14].
The fact that despite the ulcer prophylaxis, 9% of our patients had oesophagitis and 5% had gastroduodenal ulcers after the transplantation signifies that there is a potential for a large number of postoperative gastrointestinal problems. Still, the gastrointestinal mortality rate was only 0.4%, which is slightly lower than in the previous study. In our series, six patients, of whom only one was seropositive, experienced gastroduodenal ulcers soon after transplantation. Factors contributing to those were low-dose ASA in five patients, prior rejection therapy with high-dose corticosteroids in four and prior CMV infection in one patient. The association between corticosteroid treatment and ulcer disease has been controversial; but recently, the risk has been considered to be increased only in those who concurrently receive non-steroidal anti-inflammatory drugs [15]. Corticosteroids play a more important role in delaying the healing of lesions caused by non-steroidal anti-inflammatory drugs than in causing de novo ulceration [15,16]. CMV, a common post-organ-transplantation pathogen, which often is activated by rejection therapy, also causes ulcerations in the gastroduodenal mucosa [17,18]. CMV-viraemia was found in one of these six patients, but regrettably, biopsies of ulcers were not systematically examined for CMV.
Kidney transplant recipients have an increased risk of neoplasia, most of the tumours being of cutaneus origin. In a series of 2890 consecutive Finnish kidney transplant patients, 230 post-transplantation malignancies were found. Of these, 39 were of gastrointestinal origin and eight were in the gastroduodenal segment [19]. The two seropositive patients with gastroduodenal malignancies in the present series are included in these figures. Regretably, the H. pylori status of the rest of the patients has not been evaluated. There has been a lot of discussion of the role of H. pylori in the genesis of gastric carcinoma. It now seems that H. pylori is one of the cofactors involved in the development of neoplastic transformation of gastric mucosa [20]. In the present series there were two gastroduodenal malignancies in the seropositive group and none in the negative group. This raises the question whether or not it might be wise to eradicate H. pylori before transplantation.
In conclusion, H. pylori infections are common among kidney transplant patients, but they do not significantly increase the risk of postoperative gastroduodenal complications. During an acute rejection episode effective ulcer prophylaxis seems to be essential in all patients regardless of their H. pylori status, especially in patients who are also receiving prophylactic ASA treatment.
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Acknowledgments |
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Notes |
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References |
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