Association of Helicobacter pylori IgA antibodies with the risk of peptic ulcer disease and gastric cancer

AIM: To compare the prevalence of Helicobacter pylori (H pylori) IgG and IgA antibodies between adult subjects, with defined gastric diseases, nondefined gastric disorders and those representing the population. METHODS: Data on H pylori IgG and IgA antibodies, determined by enzyme immunoassay, were analyzed in 3 252 subjects with DGD including 482 patients with gastric ulcer, 882 patients with duodenal ulcer, 1 525 patients with chronic gastritis only and 363 subjects with subsequent gastric cancer, 19 145 patients with NoDg and 4 854 POPUL subjects. The age-adjusted prevalences were calculated for 1-and 20-year age cohorts. RESULTS: The prevalences of IgG antibodies were equally high (89-96%) in all 20-year age cohorts of the DGD groups, whereas the prevalences of IgG antibodies were lower and increased by age in the POPUL and NoDg groups. The prevalences of IgA antibodies were also higher in the DGD groups; among them CA (84-89%) and GU groups (78-91%) showed significantly higher prevalences than DU (68-77%) and CG patients (59-74%) (OR 2.49, 95%CI 1.86-3.34 between the GU and DU groups). In the CA, GU, and DU groups, the IgA prevalences showed only minor variation according to age, while they increased by age in the CG, POPUL, and NoDg groups (P≤0.0001). The IgA response, but not the IgG response, was associated with an increased risk of CA (OR 2.41, 95%CI 1.79-3.53) and GU (OR 2.57, 95%CI 1.95-3.39) in comparison with CG patients. CONCLUSION: An IgA antibody response during H pylori infection is significantly more common in CA and GU patients as compared with CG patients.     

Anti-CagA and anti-VacA antibodies in Helicobacter pylori-infected patients with and without peptic ulcer disease in Serbia and Montenegro

BACKGROUND: The expression of two Helicobacter pylori proteins, CagA and VacA, is associated with more severe pathogenesis and clinical outcomes of the infection. However, this association varies among geographical regions and ethnic groups. We therefore evaluated CagA and VacA seroprevalence in H. pylori-positive dyspeptic patients in Serbia and Montenegro. METHODS: In 173 consecutive dyspeptic patients referred to endoscopy (67M, mean age 49 +/- 15, 76 smokers), immunoblot assay was used to detect serum antibodies against CagA and VacA. Presence of H. pylori infection was assessed using a rapid urease test (RUT), routine histology and serology (anti-IgG ELISA). Duodenal ulcer (DU) was diagnosed in 28, gastric ulcer (GU) in 3 and non-ulcer dyspepsia (NUD) in the remaining 142 patients. RESULTS: 129 (74.6%) patients were H. pylori-positive, 27 (96.4%) with DU, 3 (100%) with GU and 99 (69.7%) with NUD (P < 0.01); 121 (93.8%) patients carried anti-CagA antibodies and there was no difference between the DU and NUD groups. VacA antibodies were detected in sera of 50 (38.75%) and were more prevalent in patients with DU compared to the NUD group (P < 0.05). CONCLUSIONS: In Serbia and Montenegro there is high seroprevalence of CagA-positive H. pylori strains in dyspeptic patients with and without peptic ulcer, while VacA-positive strains are more closely related to peptic ulcer disease.     

Association between the IgG subclass response, inflammation and disease status in Helicobacter pylori infection

BACKGROUND: In many viral, bacterial and parasitic infections the Immunoglobulin G (IgG) subclass response has been shown to correlate with severity of inflammation and disease outcome. The aim of the present study was to investigate the association between the IgG subclass response to Helicobacter pylori infection and disease and inflammation. METHODS: Eighty-three symptomatic patients undergoing endoscopic examination were included in the study. Upon endoscopic examination, the presence of ulceration was noted and biopsy specimens were collected from the gastric antrum, body and transitional zone. Blood was also collected from each patient. Gastric biopsy sections were graded using the Sydney system. H. pylori specific IgG, IgG1, IgG2, IgG3 and IgG4 were measured by ELISA. The IgG subclass was also examined retrospectively in sera collected from 20 patients previously proven to have duodenal ulcer (DU). RESULTS: The results of histological examination and IgG serology showed 35 subjects to be H. pylori negative and 48 to be H. pylori positive. Of the 48 H. pylori positive subjects, 25 were diagnosed with functional dyspepsia (FD), 14 with current DU and 9 with evidence of past DU. Significantly higher levels of IgG2 antibodies were found in patients with DU as compared with patients with FD (P < 0.01). In addition, significantly higher IgG3 subclass antibody levels were associated with chronic inflammatory cells in the body (P < 0.05) and active inflammatory cells in the transitional zone (P < 0.01). A significantly increased level of IgG1 antibodies was associated with lower levels of colonization in the gastric antrum. CONCLUSION: The results of this study suggest that the IgG subclass response in subjects infected with H. pylori may be a marker of DU disease as well as increased levels of inflammation.     

消化性溃疡患者血管活性肠肽与十二指肠胃反流和幽门螺杆菌感染关系的研究

背景：消化性溃疡（PU）和十二指肠胃反流（DGR）患者的血浆血管活性肠肽（VIP）含量常高于正常水平，而幽门螺杆菌（H.pylori)感染可能参与PU的发病。目的：探讨PU患者的VIP和DGR和H.pylori感染的关系。方法：采用放射免疫测定（RIA）检测34例胃溃疡（GU）患者、42例十二指肠球部溃疡（DU）患者和30例健康人的血浆VIP含量；放射性核素^99mTc-EHIDA显像法测定DGR；双抗体夹心酶联免疫吸附测定（ELISA）检测血清H.pylori IgG抗体，Giemsa染色检测胃黏膜H.pylori。结果：GU组的血浆VIP含量显著高于DU组和正常对照组（P＜0．01）；DGR阳性率亦显著高于DU组（P＜0．05）。DGR阳性组的血浆VIP含量显著高于DGR阴性组（P＜0．01）。H.pyori阳性组的血浆VIP含量显著低于H.pylori阴性组（P＜0．05）。结论：PU患者血浆VIP含量升高可能是DGR发生的重要因素之一。     

胃癌与十二指肠溃疡患者血清胃蛋白酶原比较

目的 比较胃癌患者与十二指肠溃疡患者血清胃蛋白酶原水平的差异及探讨其与H．pylori感染的关系。方法 采用时间分辨荧光免疫分析方法检测108例胃癌和96例十二指肠溃疡患者血清胃蛋白酶原Ⅰ、Ⅱ（PGⅠ，PGⅡ），ELISA方法检测血清H．pylori抗体。结果 胃癌和十二指肠溃疡患者之间PGⅠ水平有显著性差异，胃癌组和十二指肠溃疡组中H．pylori阳性和阴性间PGⅠ、PGⅡ、PGⅠ，PGⅡ水平等无显著性差异。结论 胃癌患者血清PGⅠ水平显著低于十二指肠溃疡患者，H．pylori感染对胃癌和十二指肠溃疡患者血清胃蛋白酶原水平和PGⅠ，PGⅡ比值均无影响。     

Non-Helicobacter pylori and non-NSAID peptic ulcer disease in the Japanese population

BACKGROUND: Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs) are recognized as the major causes of peptic ulcer disease. The status of H. pylori infection in the background population may influence the incidence of H. pylori-negative peptic ulcer disease. OBJECTIVE: To examine the incidence of H. pylori-negative peptic ulcer disease without intake of NSAIDs in Japan. PATIENTS: A total of 398 patients who had no eradication therapy for H. pylori prior to this study, including 246 patients with gastric ulcer (GU) and 152 patients with duodenal ulcer (DU), were enrolled. METHODS: H. pylori status was assessed by rapid urease tests, histological examinations (haematoxylin & eosin stain, Giemsa stain and/or immunostaining) and serum IgG antibody. Two biopsy specimens were taken from the antrum within 3 cm of the pyloric and two from the middle corpus of the stomach, along the greater curvature. Patients were asked a series of questions regarding risk factors, including the use of NSAIDs. The presence of gastritis, gastric atrophy and intestinal metaplasia was examined according to the updated Sydney system. RESULTS: Of the 246 patients with GU, 12 patients (4.9%) were considered to be H. pylori-negative. Of the 152 patients with DU, two patients (1.3%) were considered to be H. pylori-negative. Hence, a total of 14 patients were found to be H. pylori-negative. Nine of them were taking NSAIDs. Consequently, the frequency of H. pylori-negative ulcer without intake of NSAIDs was 1.3%. There was no significant difference in the frequencies of H. pylori-negative patients between the GU and DU groups. CONCLUSION: The incidence of H. pylori-negative peptic ulcer disease without intake of NSAIDs was very low in the Japanese population.     

Clinical relevance of Helicobacter pylori CagA-positive strains: gastroduodenal peptic lesions marker.

OBJECTIVES: peptic ulcer is characterized by its recurrent nature, which necessitates maintenance treatment in most patients. But this natural history can be changed in patients with peptic ulcer associated to Helicobacter pylori, as shown by the low rates of recurrence and decreased hemorrhagic recidivism associated with this infection. Whether CagA or VacA strains are associated with a greater risk of peptic ulcer is controversial. This study was designed to examine endoscopic findings and their relation with H. pylori phenotype (CagA or VacA). METHODS: 106 selected dyspeptic patients underwent upper gastrointestinal tract endoscopic examination between September 1996 and May 1997 [69 with H. pylori (Hp) and 37 without this infection]. Endoscopic findings were classified as gastric ulcer (GU), duodenal ulcer (DU), gastric erosions (GE), duodenitis (Du), chronic gastritis (CG) and normal mucosa (NM). Hp phenotype was analyzed with a western blot test. RESULTS: 75% of H. pylori strains were CagA-positive and 54.2% were VacA-positive. 82.4% of the cases of DU were associated with a CagA+ phenotype, but the association was not statistically significant. Otherwise 100% of gastric ulcers were associated with CagA+ strains (p < 0.005). VacA phenotype was not associated with any particular endoscopic finding. Peptic ulcer (DU or GU) was also associated with the CagA+ phenotype (p < 0.05). CONCLUSIONS: the CagA+ H. pylori phenotype seems to be a peptic lesion marker, but was more frequently related with GU than with DU in our sample of Spanish patients.     

Association of CagA and VacA presence with ulcer and non-ulcer dyspepsia in a Turkish population

AIM: The mostly known genotypic virulence features of H. pylori are cytotoxin associated gene A (cagA) and Vacuoliting cytotoxin gene A (VacA). We investigated the association of these major virulence factors with ulcer and non-ulcer dyspepsia in our region. METHODS: One hundred and forty two dyspeptic patients were studied (average age 44.8+/-15.9 years, range 15-87 years, 64 males and 78 females). Antral and corpus biopsies were taken for detecting and genotyping of H. pylori. 107 patients who were H. pylori positive by histological assessment were divided into three groups according to endoscopic findings: Duodenal ulcer (DU), gastric ulcer (GU) and non-ulcer dyspepsia (NUD). The polymerase chain reaction (PCR) was used to detect CagA and VacA genes of H. pylori using specific primers. RESULTS: H. pylori was isolated from 75.4 % (107/142) of the patients. Of the 107 patients, 66 (61.7 %) were cagA-positive and 82 (76.6 %) were VacA-positive. CagA gene was positively associated with DU and GU (P<0.01, P<0.02), but not with NUD (P>0.05). Although VacA positivity in ulcer patients was higher than that in NUD group, the difference was not statistically significant (P>0.05). CONCLUSION: There is a significantly positive association between CagA genes and DU and GU. The presence of VacA is not a predictive marker for DU, GU, and NUD in our patients.     

Anti Helicobacter pylori IgG and IgA response in patients with gastric cancer and chronic gastritis

BACKGROUND/AIMS: Immune response against Helicobacter pylori is important for the course and outcome of infection. We conducted study looking for the difference in anti H. pylori IgG and IgA between patients with intestinal type of gastric cancer, superficial and atrophic gastritis. METHODOLOGY: For this study, 133 patients infected with H. pylori were enrolled: 50 with superficial gastritis, 42 with atrophic gastritis and 41 with gastric cancer. Anti H. pylori IgG and IgA ELISA tests were performed. The difference in antibody titers of IgG and IgA, frequency of IgA > IgG ratio and combination of low IgG and IgA > IgG ratio were analyzed. RESULTS: The patients with gastritis had higher titer of IgG that the patients with gastric cancer (p < 0.01). The patients with superficial gastritis had higher titer of IgA than the patients with gastric cancer (p < 0.05). IgA > IgG ratio is more frequent in patients with gastric cancer than in the patients with superficial gastritis (p < 0.01). Low IgG and IgA > IgG is more frequent in the patients with gastric cancer than in the patients with gastritis (p < 0.01). CONCLUSIONS: The patients with gastric cancer elicit different anti H. pylori IgG and IgA response than the patients with superficial and atrophic gastritis. Low IgG and IgA predominance seems characteristic for gastric cancer.     

Oxidative stress in gastric mucosa in Helicobacter pylori infection.

BACKGROUND: Infection with Helicobacter pylori is believed to be associated with generation of reactive oxygen molecules which leads to oxidative stress in the gastric mucosa; but the relation between oxidative stress and gastrointestinal mucosal damage has not been documented. AIM: To look for evidence of oxidative stress and lipid peroxidation in the gastric mucosa in H. pylori-associated peptic ulcer. METHODS: 34 duodenal ulcer (DU) patients with H. pylori infection, 14 DU patients without H. pylori infection and 10 healthy subjects without H. pylori infection were studied. H. pylori infection was diagnosed by histology and rapid urease test on endoscopic biopsies from the gastric body and antrum. Reduced glutathione (GSH) and malondialdehyde (MDA) content were measured in biopsies taken from the gastric antrum. Statistical analysis was done using Student's t test. RESULTS: Tissue levels of GSH were significantly lower (91.7 [35.4] nmole/100 mg versus 147.3 [41.2] nmole/100 mg; p < 0.001) and MDA higher (163.0 [83.4] nmole/100 mg versus 109.2 [51.3] nmole/100 mg; p < 0.01) in patients with DU associated with H. pylori infection as compared to those without H. pylori infection. GSH levels were significantly lower and MDA levels higher in DU patients with or without H. pylori infection as compared to control subjects. Serum MDA levels in DU patients with H. pylori infection were also significantly higher than in patients without H. pylori infection. CONCLUSION: Depletion of gastric mucosal glutathione in H. pylori-infected DU patients may be due to failure of the antioxidant defense system. Failure of the glutathione-dependent defense system results in accumulation of free radicals which can initiate membrane damage by lipid peroxidation.     

Gastric and duodenal ulcer in the same patient

No extensive endoscopic studies have been performed on the prevalence and the clinical outcome of association of gastric ulcer (GU) and duodenal ulcer (DU). The present investigation, partially retrospective and partially prospective, takes into account 715 patients with active ulcer demonstrated by endoscopy, followed-up for a mean period of 3.8-years; 23 of them (3.2%) were found to have synchronous or asynchronous gastric and duodenal ulcers. The following characteristics were investigated: age of onset of both diseases, ulcer family history, cigarette and alcohol consumption, nonsteroidal anti-inflammatory drugs abuse, serum pepsinogen group I, ABO and Lewis blood groups, healing and relapse rate under H2-blocker treatment. The first diagnosis (by either X-Ray or endoscopy) was DU in 500 subjects (70%), GU in 210 (29.3%) and synchronous gastric and duodenal ulcers in 5 (0.7%). After a median period of 10 years, 2.8% of DU patients developed a GU; after 2-12 yrs 1.9% of GU patients developed a DU. The clinical and biochemical findings of our GU/DU patients suggest that the two ulcers are related by chance. In conclusion: asynchronous GU/DU patients do not seem to have a distinct disease in the large spectrum of ulcer disease. Larger studies must be planned on synchronous GU/DU with the aim of assessing whether or not it represents a particular type of ulcer disease.     

Genetic alterations in benign lesions： Chronic gastritis and gastric ulcer

AIM:To investigate the occurrence of chromosome 3,7,8,9,and 17 aneuploidies,TP53 gene deletion and p53protein expression in chronic gastritis,atrophic gastritisand gastric ulcer,and their association with H pylori in-fection.METHODS:Gastric biopsies from normal mucosa(NM,n=10),chronic gastritis(CG,n=38),atrophic gastritis(CAG,n=13)and gastric ulcer(GU,n=21)were studiedusing fluorescence in situ hybridization(FISH)and im-munohistochemical assay.A modified Giemsa stainingtechnique and PCR were used to detect H pylori.An as-sociation of the gastric pathologies and aneuploidies withH pylori infection was assessed.RESULTS:Aneuploidies were increasingly found from CG(21%)to CAG(31%)and to GU(62%),involving mainlymonosomy and trisomy 7,trisomies 7 and 8,and triso-mies 7,8 and 17,respectively.A significant associationwas found between H pylori infection and aneuploidiesin CAG(P=0.0143)and GU(P=0.0498).No TP53 dele-tion was found in these gastric lesions,but p53-positiveimmunoreactivity was detected in 45%(5/11)and 12%(2/17)of CG and GU cases,respectively.However,therewas no significant association between p53 expressionand H pylori infection.CONCLUSION:The occurrence of aneuploidies in be- nign lesions evidences chromosomal instability in earlystages of gastric carcinogenesis associated with H pyloriinfection,which may confer proliferative advantage.Theincrease of p53 protein expression in CG and GU may bedue to overproduction of the wild-type protein related toan inflammatory response in mucosa.     

Alpha1-antitrypsin deficiency may be a risk factor for duodenal ulcer in patients with Helicobacter pylori infection

BACKGROUND: Most individuals with Helicobacter pylori infection in Western countries have no evidence of peptic ulcer disease (PUD). We therefore assessed the PiZ deficiency variant of the major plasma protease inhibitor alpha1-antitrypsin (alpha1AT) as a risk factor for PUD in H. pylori-infected individuals. METHODS: The cohort comprised 100 patients with endoscopically or surgically proven PUD (30 patients with duodenal ulcer (DU) and 70 patients with gastric ulcer (GU)) and 162 age- and sex-matched controls with PUD-negative endoscopic findings and no history of PUD. Plasma samples were screened for alpha1AT deficiency (PiZ) with an enzyme-linked immunosorbent assay (ELISA) and phenotyped by isoelectric focusing. H. pylori infection was evaluated with an IgG ELISA technique. RESULTS: Among the 262 patients 17 (6.5%) were positive for the PiZ alpha1AT deficiency, a frequency of the same magnitude as in the Swedish general population (4.7%). Of the PiZ carriers 76% (13 of 17) had H. pylori antibodies compared with 61% (151 of 245) of the non-PiZ carriers (NS). The prevalence of DU tended to be higher in H. pylori-positive PiZ carriers than in non-PiZ carriers (15.4%, 4 of 26 versus 0 of 4). Furthermore, among patients with DU a high PiZ allele frequency (13.3%, 4 of 30) was found compared with the general population (4.7%) (odds ratio (OR), 3.2; 95% confidence interval (CI), 1.09-8.94; P = 0.02). All DU patients carrying the PiZ allele were positive for H. pylori. In addition, four of five PiZ carriers with H. pylori infection and PUD had DU. CONCLUSIONS: The PiZ allele may be a contributing factor in the development of DU in H. pylori-positive individuals.     

Concentrations of α- and β-defensins in gastric juice of patients with various gastroduodenal diseases

AIM: To determine the concentration of α- and β-defensins in gastric juice of patients with various gastroduodenal diseases. METHODS: Concentrations of human neutrophil peptides (HNPs) 1-3, the major forms of α-defensins, and human β-defensin (HBD)-I and HBD-2 were measured by radioimmunoassay in plasma and gastric juice of 84 subjects, consisting of 54 Helicobacter pylori-infected and 30 uninfected subjects. They included 33 patients with chronic gastritis (CG), 12 with gastric ulcer (GU), 11 with duodenal ulcer (DU), 11 with benign gastric polyp (BGP) and 16 with normal mucosa (N group) on upper endoscopy. Plasma pepsinogen Ⅰ and Ⅱ levels, biomarkers for gastric mucosal inflammation and atrophy, were also measured. RESULTS: Gastric juice HNPs 1-3 levels in patients with CG, GU and BGP were significantly higher than those in patients with DU and N. Gastric juice HBD-2 concentrations in patients with CG and GU were significantly higher than those in the N group, but were significantly lower in DU patients than in GU patients. Gastric juice HBD-1 levels and plasma levels of these peptides were similar in the patient groups. Concentrations of gastric juice HNPs 1-3 and HBD-2 of in H pylori-infected patients were significantly different from those in uninfected subjects. HNPs 1-3 concentrations in gastric juice correlated negatively with plasma pepsinogen Ⅰ levels and Ⅰ/Ⅱ ratios. HBD-2 levels in gastric juice correlated positively and negatively with plasma pepsinogen Ⅱ concentrations and Ⅰ/Ⅱ ratios, respectively. CONCLUSION: HNPs 1-3 and HBD-2 levels in gastric juice are diverse among various gastrointestinal diseases, reflecting the inflammatory and atrophic events of the background gastric mucosa affected by H pylori。     

Comparison of gastric histology among Swedish and Japanese patients with peptic ulcer and Helicobacter pylori infection

BACKGROUND: The natural course of Helicobacter pylori gastritis may vary between different ethnic groups. Gastric histopathology and the occurrence of H. pylori organisms in the stomach were investigated in healed duodenal (DU) and gastric (GU) ulcer patients recruited in Sweden (S) and Japan (J) in an identical trial. METHODS: In 203 patients (JGU = 39, JDU = 55, SDU = 109), various morphological gastritis variables and H. pylori were assessed from biopsy specimens obtained using a specific sampling protocol and interpreted according to guidelines of the updated Sydney grading system. RESULTS: The ratio of GU:DU was observed to be very different between the recruited Japanese (39:55) and Swedish (0:109) patients. A comparison of data from SDU and JDU showed that the prevalence of H. pylori infection and the antral predominant gastritis demonstrated by both SDU and JDU were essentially identical. A comparison of data from JDU and JGU demonstrated a greater prevalence of H. pylori infection in the antrum, but not corpus, of JDU compared to JGU patients. The prevalence of atrophy and intestinal metaplasia was higher in both the antrum and corpus of JGU compared to JDU in all patients. CONCLUSIONS: The site specified biopsy methodology and standardized interpretation criteria utilized in this study clearly show that the histotopographic profile of Swedish and Japanese DU patients is essentially the same.     

Gastric Carcinoid Tumors Without Autoimmune Gastritis in Japan: A Relationship with Helicobacter pylori Infection

In Japan, most cases of gastric carcinoid tumor (GCT) are unassociated with either autoimmune gastritis (AIG) showing type-A chronic atrophic gastritis (CAG-A) or Zollinger-Ellison syndrome (ZES). However, the pathogenesis of this tumor remains unknown. Recent studies have determined that Helicobacter pylori infection induces gastric carcinoid in Mongolian gerbils and that H. pylori lipopolysaccharide exerts a mitogenic effect on ECL cells. We examined five patients with histologically diagnosed GCT, 40 patients with H. pylori-positive gastric ulcer (Hp+GU), 24 patients with H. pylori-positive duodenal ulcer (Hp+DU), and 12 patients with AIG showing CAG-A topographically. We compared the prevalence of H. pylori infection, and the levels of gastrin and pepsinogen (PG) in the serum of patients with GCT with those of patients with Hp+GU, or Hp+DU, and AIG. We also investigated the histological characteristics of the tumor and the gastric corpus mucosa in the GCT patients. The levels of serum gastrin and PG I and II were measured using an RIA kit. In all five (100%) patients with GCT, H. pylori infection was present, without any evidence of AIG or ZES. The serum levels of gastrin in the GCT patients were higher than those in either Hp+GU or Hp+DU patients and lower than those in the AIG patients. In contrast, serum PG I levels and the PG I/II ratio were lower in the GCT group than in the Hp+GU or Hp+DU groups. Histologically, all GCTs were ECL cell tumors and peritumoral corporal mucosal atrophy was observed in four of the five patients with GCT. In conclusions, H. pylori infection and hypergastrinemia were found in the patients with GCT without AIG. This finding suggests that H. pylori infection may induce corporal mucosal atrophy and hypergastrinemia that can produce a GCT with time.     

胃、十二指肠溃疡幽门螺杆菌感染及相关病因回顾性分析204例

目的:研究福建省立医院胃、十二指肠溃疡患者幽门螺杆菌(H.pylori)感染及其他致病因素对疾病发生的作用.方法:选取2003-2008年福建省立医院胃镜中心进行检查并确诊为消化性溃疡的患者204例,所有患者在胃镜检查前记录详细情况,包括H.pylori感染,胃黏膜活检尿素酶法(14C-UBT),吸烟史(每日>10支)...     

Helicobacter pylori Infection and Serum Pepsinogen A, Pepsinogen C, and Gastrin in Gastritis and Peptic Ulcer: Significance of Inflammation and Effect of Bacterial Eradication

Objectives: To study the relationship between Helicobacter pylori infection, gastric inflammatory scores, and fasting gastrin and pepsinogen A and C concentrations, and to evaluate the effect of treatment on these parameters. Methods: Gastrin and pepsinogen A and C concentrations were measured in 36 patients with gastritis, 10 gastric ulcer patients, 12 duodenal ulcer patients, and in 15 subjects with normal gastric mucosa, by standard radioimmunoassay techniques. Fifteen patients with H. pylori infection underwent triple therapy (bismuth subsalicylate, amoxicillin, metronidazole) and were reassessed 1 month later. Results: Fasting gastrin and pepsinogen A and C concentrations were significantly higher in H . pylori-positive gastritis and peptic ulcer patients than in subjects with normal mucosa and in patients with H.pylori -negative gastritis. There was a significant correlation between inflammatory scores and serum gastrin ( r = 0.45, p < 0.0001), and pepsinogen A ( r = 0.33, p < 0.006) and pepsinogen C ( r = 0.55, p < 0.0001) concentrations. Neither sex nor age affected basal gastrin and pepsinogen concentrations. Eradication of H. pylori infection was successful in 12 patients and resulted in a significant fall in serum gastrin and in pepsinogen A and C concentrations, and in a concomitant improvement of the inflammatory scores. Serum peptide levels and gastritis scores were unchanged in those patients in whom H. pylori infection persisted. Conclusions: These findings suggest that hy-pergastrinemia and hyperpepsinogenemia are secondary to H. pylori infection and are related to mucosal inflammation.     

Prevalence and pathogenesis of duodenal ulcer in chronic alcoholic pancreatitis

BACKGROUND: The prevalence of duodenal ulcer (DU) has been considered high in patients with chronic pancreatitis; however, its pathogenesis is unclear. We hypothesized that Helicobacter pylori infection plays the major pathogenetic role. STUDY: One hundred seven cases (97 men, 10 women) of chronic alcoholic pancreatitis (CAP) were prospectively investigated from 1997 to 2001. One hundred thirty-seven DU patients and 59 nonulcer dyspepsia patients formed the two control groups. Pancreatic function was evaluated by determination of fecal fat excretion and fasting blood glucose concentration. Upper gastrointestinal endoscopy was performed in all patients, and gastric mucosal biopsies were taken for assessment of H. pylori infection with a modified Giemsa stain and rapid urease test. RESULTS: Fifteen (14%) of the 107 patients with CAP had active DU. There was a trend toward an association between the presence of diabetes mellitus and/or steatorrhea and the occurrence of DU in patients with CAP (p = 0.06). The rate of H. pylori infection was significantly higher in patients with CAP and DU than in those with only CAP (86.7% vs. 54.3%, p = 0.02) but the rate similar to that in patients with simple DU (75.2%). Trends toward higher prevalence of H. pylori infection in CAP with DU were noticed when they were compared with the nonulcer dyspepsia group (86.7% vs. 66.1%). There was no significant difference in prevalence of H. pylori between CAP patients without DU and dyspeptic patients (54.3% vs. 66.1%). CONCLUSIONS: These data demonstrate that the prevalence of DU in CAP is relatively high. H. pylori infection seems to play the major pathogenetic role in DU associated with CAP.     

Recurrence of Helicobacter pylori infection and the long-term outcome of peptic ulcer after successful eradication in Japan.

Recurrence of peptic ulcer after successful eradication of Helicobacter pylori is closely associated with reinfection. The aim of this study was to examine the recurrence of peptic ulcer and reinfection with H. pylori after successful eradication. To eradicate H. pylori infection, patients with active peptic ulcer disease were assigned to two treatment groups depending on the year of their enrollment (AM group and OAMR group). Patients in the AM group received 400 mg of cimetidine twice per day, 300 mg of amoxicillin three times per day, and 250 mg of metronidazole three times per day for 2 weeks. Patients in the OAMR group received 20 mg of omeprazole once per day, 500 mg of amoxicillin granules three times per day, 250 mg of metronidazole three times per day, and 150 mg of roxithromycin twice per day for 1 week. After endoscopy verified ulcer scarring and successful eradication of H. pylori infection, study patients were followed up monthly and did not undergo acid-suppressive therapy. Endoscopy was performed at 6-month intervals for the 1st year. After the 1st year, follow-up endoscopies were performed annually. In total, 107 patients with peptic ulcer (duodenal ulcer [DU], 65; gastric ulcer [GU], 42) were followed up for a mean period of approximately 2 years. Recurrence of infection occurred in 10 (9.3%) of 107 patients (AM group, 9; OAMR group, 1) after 210 patient-years of follow-up; the recurrence rate was 4.8% per patient-year. Recurrence of H. pylori infection was significantly higher in the AM group (23.1%) than in the OAMR group (1.5%). H. pylori infection recurred in two patients 6 months after eradication therapy, in seven 1 year after, and in one 2 years after. Thereafter, no further cases of H. pylori recurrence were observed. During follow-up periods, seven cases of ulcer recurrence were observed (DU, 4; GU, 3). The rate of peptic ulcer recurrence within 2 years after eradication therapy was significantly higher than that after more than 2 years. Four cases of ulcer recurrence (DU, 3; GU, 1) also had recurrence of H. pylori infection. One recurrent case of DU without reinfection was associated with nonsteroidal anti-inflammatory drugs. The remaining two cases of GU recurred without H. pylori reinfection. In conclusion, peptic ulcer recurrence rarely occurred (3 [2.9%] of 103) in patients cured of H. pylori infection. Reinfection after apparent successful eradication was rarely noted when a powerful therapeutic regimen in eradication was used. Therefore, to eradicate H. pylori, a highly effective therapeutic regimen should always be used.