Reports of strong associations in small observational studies without appropriate adjustment for potential confounding factors were not generally confirmed by larger and better- design ed studies .
The available evidence indicates that there is no strong association between H pylori and dyspepsia , but there is insufficient evidence to confirm or refute the existence of a modest association
BACKGROUND Previous studies have yielded conflicting results and substantial uncertainty about any independent association of Helicobacter pylori infection with dyspepsia , and about any benefits of antibiotic treatments for nonulcer or uninvestigated dyspepsia .
OBJECTIVES To perform a systematic review of the literature to determine whether chronic infection with H pylori is relevant to nonulcer or uninvestigated dyspepsia .
Helicobacter pylori Infection and the Risk for Duodenal and Gastric Ulceration
Infection with Helicobacter pylori probably increases the risk for developing duodenal and gastric ulcer disease . Previous studies have shown that 75 % to 100 % of patients with duodenal ulcer and 35 % to 86 % of patients with gastric ulcer have evidence of an H. pylori infection [ 1 ] . The finding that eradication of H. pylori in patients with duodenal ulcer is associated with a statistically significant decrease in the recurrence rate of the disease further supports the association [ 2 - 5 ] . However , these observations may just reflect the frequent coexistence of duodenal ulcer with antral gastritis [ 6 ] , which has been shown to be caused by H. pylori [ 7 , 8 ] . Wormsley [ 9 ] has noted that the Henle-Koch postulates have not been satisfied for causation of duodenal ulcer by H. pylori because the organism has not been shown to produce the disease . The evidence is weaker that H. pylori causes gastric ulcer because only a single study with 26 patients has shown that antimicrobial therapy directed against H. pylori decreased the gastric ulcer recurrence rate [ 5 ] . None of the previous studies evaluated patients with duodenal or gastric ulcers before they were diagnosed or hospitalized with their disease . The usual temporal sequence is that patients with peptic ulcer disease are examined to detect H. pylori infection at the time the diagnosis is made or after they have had treatment to eradicate the organism . Consequently , peptic ulceration could possibly predispose persons to colonization by H. pylori [ 9 ] . We did a prospect i ve study in a large population -based cohort using serum specimens that were obtained from study participants before they were diagnosed with peptic ulcer . We tried to determine whether H. pylori infection , as shown by the presence of specific IgG antibodies , is a risk factor for the subsequent development of either duodenal or gastric ulceration . Methods Study Population Japanese-American men born from 1900 to 1919 , who were identified by the Honolulu Heart Program in 1965 by using the comprehensive 1942 Selective Service draft registration files [ 10 ] , composed the study population . Of 11 148 eligible men , 8006 ( 72 % ) were interviewed and examined from 1965 to 1968 , 180 ( 2 % ) died before they could be examined , and 2962 ( 26 % ) did not participate in the program . Study participants ranged in age from 45 to 68 years . The data collected included birthplace , marital status , history of alcohol use , blood pressure , and body mass index ( the weight in kilograms divided by the square of the height in meters ) . Serum cholesterol values were determined by the Auto Analyzer N-24A method , and serum glucose values were determined by the Auto Analyzer N-2B method 1 hour after a 50-g glucose load had been given [ 11 ] . A total of 7498 ( 94 % ) men returned for a second examination between 1967 and 1970 , and a serum specimen was obtained at this time . Serum specimens for a 20 % r and om sample of the men were sent to the U.S. Public Health Service Hospital in San Francisco , whereas specimens for the remaining 5924 men were stored at 20C at the study site . Four hundred eighty-one patients with previous gastrectomy or a previous diagnosis of peptic ulcer disease were excluded from the study . The average age of the remaining 5443 patients at the time of their second examination was 56.6 years . Surveillance Methods Surveillance of the cohort to identify incident patients with peptic ulcer was done by a continuous review of discharge records of all general hospitals on Oahu . Based on a 19-year follow-up survey of the study patients from the time of their examination in 1965 to 1968 , only 1.3 % of the men could not be located on Oahu . Thus , surveillance was nearly complete . Two hundred fifty-eight patients were hospitalized with peptic ulcer disease from 1968 to 1989 . One hundred sixty ( 62 % ) patients had their diagnosis confirmed by examination of tissue obtained by either surgery or biopsy , 36 ( 14 % ) were diagnosed by radiologic examination , and 62 ( 24 % ) were clinical ly diagnosed based on the endoscopic or surgical report of the presence of an ulcer . One hundred sixty-nine incident patients had gastric ulcer , 73 had duodenal ulcer , and 16 had gastric and duodenal ulcers . Seventeen of the 169 patients with gastric ulcer , 6 of the 73 patients with duodenal ulcer , and 2 of the 16 patients with gastric and duodenal ulcers were removed from study because they had an insufficient amount of serum in the freezer repository . Selection of Controls Each of the remaining patients was matched with one control from the study cohort based on age at examination ( 47 to 70 years ) and date of serum collection . If a potential control had a diagnosis of gastric cancer before or after the serum was obtained , he was excluded from the study . As a consequence , 160 patients ( 3.1 % ) were removed from the control pool of 5185 men because of the reported association between H. pylori infection and gastric cancer [ 12 , 13 ] . Of the remaining 5025 men , 336 ( 6.7 % ) were excluded because they previously had cardiovascular disease or other cancer , and 1532 ( 30.5 % ) were excluded because they were diagnosed with cardiovascular disease or other cancer after their serum collection . This exclusion was done because the serum specimens from these patients are going to be used for other studies . A total of 3157 patients remained in the pool of controls from which 233 ( 7.4 % ) were matched to incident case- patients with peptic ulcer . Each control participant was alive at the time of hospitalization of the matched case-patient , so that death was not a competing factor . Serologic Testing The presence of serum IgG antibodies to H. pylori was determined by enzyme-linked immunosorbent assay ( ELISA ) , using the Pyloristat kit ( Whittaker Bioproducts , Inc. , Walkersville , Maryl and ) . As vali date d by the manufacturer , the results of this assay closely mirror those of a previously described IgG ELISA [ 13 - 18 ] . In brief , serum specimens from patients were diluted 1:20 for use in the kit , and IgG levels of sera were determined according to the manufacturer 's instructions . The serum specimens were coded so that the laboratory technician could not distinguish case- patients from controls . A ratio of 1.00 or greater was considered positive , a ratio of less than 0.80 was considered negative , and a ratio of 0.80 to 0.99 was considered equivocal , as calibrated in the kit . Two patients with gastric ulcer and two patients with duodenal ulcer or their controls had equivocal values , so they were excluded from the study . Statistical Analysis A matched casecontrol study design was used to identify the patients and controls for serum tests . As a result , odds ratios , based on the results of the H. pylori IgG antibody test , were determined using conditional logistic regression methods [ 19 ] . When odds ratios were indeterminable , approximate confidence intervals ( CIs ) were determined by the method of Breslow and Day [ 19 ] . Tests for trend in the logit of risk were derived from conditional logistic regression models by using grouped H. pylori test results ( coded as 1 , 2 , 3 , and 4 ) . All conditional logistic regression models were fitted using iterative maximum likelihood methods and a special application of the proportional hazards regression model [ 20 ] . Results The characteristics of the 229 patients with peptic ulcer and of their matched controls are presented in Table 1 . The two groups of men were similar with respect to demographic characteristics and laboratory values . Table 1 . Characteristics of Patients with Peptic Ulcer and of Controls The mean age at diagnosis was 67.5 years ( range , 52.7 to 87.2 years ) for the 150 patients with gastric ulcer , 64.5 years ( 49.4 to 80.0 years ) for the 65 patients with duodenal ulcer , and 63.5 years ( 52.4 to 83.1 years ) for the 14 patients with gastric and duodenal ulcers . Table 2 shows the association between the H. pylori test result and peptic ulcer by specific type . Ninety-three percent ( 139 of 150 ) of the patients with gastric ulcer and 78 % ( 117 of 150 ) of the matched controls had a positive H. pylori-specific IgG antibody level , yielding an odds ratio of 3.2 ( P = 0.001 ) . ( The odds ratio is determined by dividing 32 pairs by 10 -/+ pairs . ) Ninety-two percent of the case- patients with duodenal ulcer and 78 % of the matched controls had a positive test result , yielding an odds ratio of 4.0 ( P = 0.03 ) . If a patient had either a gastric or duodenal ulcer , then the odds ratio was 3.4 ( P = 0.0001 ) . Only 14 patients had both gastric and duodenal ulcers . The odds ratio was 1.3 ( P > 0.2 ) , based on these patients . Table 2 . Odds Ratio for the Association between Helicobacter pylori Seropositivity and Type of Peptic Ulcer Because some of the hospitalized patients with peptic ulcer may have developed their ulcers after the use of adrenocorticosteroids or nonsteroidal anti-inflammatory drugs , we systematic ally review ed the hospital records of the patients . A similar review could not be done for the controls because they were not hospitalized . We found that 18 of the 150 patients with gastric ulcer and 9 of the 65 patients with duodenal ulcer had taken these medications at the time of hospitalization . If these patients and their matched controls were excluded , the odds ratio would have been 3.3 ( 95 % CI , 1.6 to 7.0 ) for gastric ulcer , 3.3 ( CI , 0.9 to 12.1 ) for duodenal ulcer , and 3.3 ( CI , 1.7 to 6.4 ) for either gastric or duodenal ulcer . Of the 215 patients with either gastric or duodenal ulcer , 100 also had a hospital-based diagnosis of cardiovascular disease or cancer .  If these patients were excluded from the study , as were controls with these diseases , 115 patients with gastric or duodenal ulcer would have remained in the study . Ninety-four percent of these case- patients and 77 % of their controls had a positive test result for H. pylori antibody . The odds ratio for peptic ulcer was 4.3 ( CI , 1.8 to 10.5 ) in this group of patients . When the patients with gastric ulcer who had positive antibody
Reports of strong associations in small observational studies without appropriate adjustment for potential confounding factors were not generally confirmed by larger and better- design ed studies .
The available evidence indicates that there is no strong association between H pylori and dyspepsia , but there is insufficient evidence to confirm or refute the existence of a modest association
BACKGROUND Previous studies have yielded conflicting results and substantial uncertainty about any independent association of Helicobacter pylori infection with dyspepsia , and about any benefits of antibiotic treatments for nonulcer or uninvestigated dyspepsia .
OBJECTIVES To perform a systematic review of the literature to determine whether chronic infection with H pylori is relevant to nonulcer or uninvestigated dyspepsia .