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k STORAGE hal J Gastroenterol 1993; 25: 419-424 ORIGINAL ARTICLES Irtput N .~ --------- . ...... .. --•-- Helicobacter pylori infection, cigarette smoking and alcohol consumption. A histological and clinical study on 286 subjects G BATTAGLIA, F DI MARIO 1, M PASINI, PM DONISI2, PAOLA DOTTO t, MARIA EUGENIA BENVENUTI, V STRACCA-PANSA2, M PASQUINO. Servizio di Gastroenterologia ed Endoscopia Digestiva, OCR Venezia, IDivisione di Gastroenterologia "R. Farini", Universith di Padova and 2Servizio di Anatomia Patologica, OCR Venezia, Italy YHelicobacter pylori (Hp) is connected with ac- tivelchronic gastritis, gastric and duodenal ulcer. It is not known whether exogenous factors are involved in Hp infection. The aim of this prospective study, per- formed on 286 consecutive subjects undergoing upper gastrointestinal endoscopy, was to evaluate the influence of smoking and alcohol consumption on Hp infectioJn. For each patient the following parameters were taken into account: sex, age, smoking (no, <10, >10 cig/day) and alcohol (no, <40, >40 g ethanol/day) intake, antiulcer therapy (no, H2-blockers, omepra- zole, sucralfate), presence of gastric or duodenal ulcer (DU). At least two biopsies from both the an- trum and the corpus were obtained for histological examination; the gastritis was classified and scored according to the Sydney system. Statistics: chi squa- red test (corrected), Fisher's exact test. Results: 43 pts had Hp +++ (27M, 16F; age 57.8 yrs, range 23- 91), 47 Hp ++ (25M, 22F; age 61.1, range 19-86), 81 Hp + (48H, 33F; age 56, range 16-84), 115 Hp- (75M, 40F; age 57.8, range 19-84). Hp infection was found to be significantly correlated with presence of ulcer symptoms, gastritis, lymphoid follicles and, among DU patients, with active DU. The other parameters considered did not influence Hp infection.1 In con- clusion smoking habits and alcohol consumption do not affect Hp infection of the stomacl~i _.1 L2dex tennsr Alcohol consumption, Dyspepsia, Gastritis, Helicobacter pylori, Intestinal metaplasia, Smoking habits. Address to correspondence: Dr. G Battaglia, Servizio di Gastroenterologia ed Endoscopia Digestiva, OCR "SS. Giovanni e Paolo", 30100 Venezia, Italy Accepted for publication: 17 June 1993 Helicobacter Pylori (Hp) is a bacterium which cau- ses active/chronic gastritis (1-12). It has been sug- gested that Hp infection is connected with duodenal ulcer (DU) onset which might explain the high rates of Hp-positive DU patients observed in a number of studies (1-4, 7, 10, 13-19)- and relapse (20-23). Mo- reover, gastric ulcer (GU) also seems to be influenced by micro-organism (1-4, 7, 10, 13, 15-17, 19). It has not been fully clarified how Hp infects humans: it ap- pears clear, however, that its prevalence increases with age and has an inverse relationship with socio- economic status, i.e. the poorer the hygienic condi- tions, the greater the degree of Hp infection (24-26). It is not known whether exogenous factors are in- volved in Hp infection: alcohol consumption has not been found to affect Hp presence (27-30) and nor has smoking (28, 30). A number of drugs have been tried in the hope of finding anti-Hp activity: among anti- ulcer medications, 1-I2-blockers have no effect on Hp gastric infection (22, 31-34), while omeprazole seems to have clearance properties (35). With this in mind, the aim of our study was to assess whether some exogenous factors, which largely affect gastroenterological patients who are referred to an endo- scopic unit, such as smoking and alcohol consumption, influence the presence of Hp in the stomach; moreover, we take into account previous anti-ulcer therapy and, in every case, we correlated such factors with Hp infection in terms of "Hp density" and severity of gastritis. We paid particular attention to dyspeptic symptoms and to histological features (inflammation, intestinal metapla- sia, lymphoid follicles). The study was performed on an unselected population of subjects undergoing upper gastrointestinal endoscopy. Patients and methods We consecutively recruited all patients referred for upper GI endoscopy to the Venice gastroenterology unit during two consecutive months. Exclusion crite- ria were: previous therapy with either colloidal bis- muth subcitrate or antibiotics, upper GI bleeding, pre- vious major GI surgery, severe portal hypertension,

420 G BATTAGLIA et al: Alcohol, smoking and Hp Table I. Clinical data in the sample studied divided according to the degree of Helicobacter pylori infection ("density" of bacte- ria in the gastric specimens of the antrum). .-•---- -..._.... _--------- ---~ • -- ~ ---- ---• -•---- ------.. .-. , ._ .... . __ ._.--- °--- - Hp density +++ ++ +_. :: - P ---------- ,..--- ------• •------------.. Total number 43 47 81 115 Males (age): 27 25 48 75 ns mean 57.8 61.1 56.0 ' 57.8 ns range 23-91 19-86 16-84 19-84 Cigarette smoking: no 34 34 55 80 <10/per day I 4 6 5 ns >I0/per day 8 9 20 30 Ethanol intake: no 19 18 43 54 <40 g/per day 19 24 35 48 ns >40 g/per day 5 5 3 13 Anti-ulcer therapy: no 19 19 26 42 H2-blockers 16 22 38 43 ns omeprazole 3 4 14 2 cytoprotectors 1 I 2 1 Ulcer-like dyspepsia/ epigastric pain 26 14 19 25 <0.0001 Gastric ulcer: active 2 4 7 9 healed 4 5 15 17 ns Duodenal ulcer: active 7 9 16 2 <0.0001 healed I 1 l 14 25 severe concomitant diseases, chronic non steroidal anti-inflammatory drugs (NSAID) use. At entry, and before upper GI endoscopy, each pa- tient gave the following data: sex, age, smoking ha- bits (average number of cigarettes smoked per day), alcohol consumption (average ethanol intake per day, in grams), current anti-ulcer therapy (H2-blockers, omeprazole, sucralfate), presence of ulcer symptoms (epigastric pain and/or "ulcer-like dyspepsia"). The upper GI endoscopy carefully registered any ul- ceration, either in the active or scarred phase, both in the stomach and in the duodenum. At least two biopsy specimens were taken from the antrum (lesser and greater curvature) and from the corpus. Another antral biopsy was done to permit rapid diagnosis of Hp infec- tion by means of a quick urease test (CP-test, Gist-bro- cades FARMA SpA). Hp infection was diagnosed when at least one of the two methods (urease test and histological evaluation) proved positive. The histologi- cal examination was in every case performed by the same two pathologists, using a blind crossover; the Sydney System classification of gastritis was used by both gastroenterologists and pathologists (36). The modified Giemsa stain (37) was used to discover Hp in the histological specimens. A semiquantitative method describes the presence of Hp in the gastric mucosa in four degrees: absent, mild (presence of bacterium. in less than 1/3 of the epithelial surface), moderate (bet- ween 1/3 and 1/2 of the epithelial surface) and severe (2/3 or more of the epithelial surface) infection. Chro- nic inflammation, related to lymphoplasmocytic in- filtration in the lamina propria and graded according to the Sydney System as mild, moderate or severe (38), was taken into account to confirm its relationship with Hp infection. Like other recent contributions, which have em- phasized the relationship between gastritis activity and histological type in the antrum and corpus (12) and the similar frequency of Hp infection in the an- trum and corpus (39), our series revealed that Hp was either present in both antrum and corpus or absent from both sites (that is, no case revealed Hp in the

G BarTACLtA er al: Alcohol, smoking and Hp 421 1 Table Ti. Histological characteristics (Sydney system) in the sample studied divided according to the degree of Helicobac- ter pylori infection ("density " of bacteria in the gastric speci- mens of the antrum). ~•~._ Hp density +++ ++ + p Total number 43 47 81 115 Inflammation: no/mild 9 6 22 49 moderate 26 39 43 52 <0.0001 severe 8 2 16 14 Intestinal metaplasia: focal 5 4 15 14 plurifocal` 1 8 10 15 ns diffuse 0 0 1 2 Lymphoid follicles 13 13 21 7 <0.001 corpus but not in the antrum or viceversa); for our purposes, we therefore only took histological findings in the antrum into account. ` Statistical analysis was performed by Student's t test for unpaired data, analysis of variance (ANOVA one way) and Fisher exact test. Values of p less than 0.05 were considered as significant. Results Two hundred and eighty-six patients entered the study; 175 were males and 1 l 1 females and their ages ranged between 19 and 91 yrs; 203 were non- smokers, and 134 teetotallers. One hundred and six subjects were not on anti-ulcer therapy, and 84 repor- ted either ulcer-like dyspespia or epigastric pain or both.. Twenty-two patients had an endoscopically documented active GU, while 41 were scarred by a previous ulcer lesion of the stomach. Thirty-four and 61 subjects presented, respectively, an active and a scarred DU. I No false-positive CP-tests..were recorded, while 64 out of 171 cases of histologically diagnosed Hp infec- tion were negative at CP-test (false-negative: 37.4%). GU patients were found Hp-positive less frequent- ly than DU patients (58.7% vs 71.6%). Non-ulcer subjects were Hp-positive in 51.6% of cases. Table I reports the clinical characteristics of the sample studied divided according to the degree of Hp infection in the antrum. Smoking habits and alcohol consumption resulted unrelated to Hp infection while, in the other hand, the greater the Hp "density" the hi- ;her the percentage of symptoms. Among DU sub- ects, patients with active lesions were more frequent- y Hp-positive than Hp-negative. Histological analysis confirmed the relationship existing between gastritis and Hp: the more "dense" its presence the higher the degree of inflammation. The presence of lymphoid follicles was strictly corre- lated to Hp presence while intestinal metaplasia resul- ted unrelated to Hp infection (Table II). Hp was not found over intestinal metaplasia except in 4 cases: 2 cases with focal intestinal metaplasia, presence of lymphoid follicles and Hp+++; I case with plurifocal intestinal metaplasia, absence of lymphoid follicles and Hp++; I case with diffuse intestinal metaplasia, absence of lymphoid follicles and Hp+++. Discussion Hp infection on human gastric mucosa is currently being investigated in many clinical studies: the ways of infection, the relationship with the various patholo- gies of the upper gastrointestinal tract (neoplasms in- cluded), the effects of different therapeutic schedules on both infection and subsequent follow-up are the main aspects studied. Up to now, little is known about the existence of any relationship between the exogenous factors in- volved in many of the upper gastrointestinal diseases, and Hp prevalence on gastric mucosa. The few data that have appeared in the Literature are substantially negative: a high prevalence of Hp positivity in 193 patients with non-ulcer dyspepsia, and the lack of a relationship between alcohol and/or cigarette con- sumption and the presence of Hp, was reported by Heatley and co-workers (28). In another study (27) alcohol consumption was found not to be involved with Hp infection. Both these studies, however, were retrospective and appeared only in abstract form. A French study on 144 patients (29) suggested that al- cohol consumption is associated with antral gastritis and only consequently with the growth of Hp; it must be emphasized, however, that the sample studied was divided according to alcohol consumption below or over 80 g per day, that is an intake twice as much as we registered, and teetotallers were not taken into consideration. Graham and coworkers, on the con- trary, in 485 healthy asyaptomatic volunteers found no association between Hp infection and smoking or alcohol consumption (30). We performed the present prospective study, specifically aimed at discovering the possible role of smoking and alcohol consumption on the Hp infection of the gastric antrum, on subjects consecutively referred to an endoscopic unit. Even though the Sydney classification of gastritis was recently the object of a number of criticisms (40), we chose to follow it since the major concern of

422 G BATTAGLIA et al: Alcohol, smoking and Hp our study was the relationship between Hp and both the above mentioned exogeneous factors: the Sydney system, in fact, seerns particularly effective in describing Hp-related histological variables. Our study found that alcohol intake and cigarette consumption did not affect Hp infection: the preva- lence of drinkers and smokers among the Hp positive and negative patients was comparable. Even when we divided the studied sample according to the density of the infection we were not able to demonstrate any relationship between these factors. Our results, there- fore, are in agreement with those obtained in asymp- tomatic volunteers studied by means of an ELISA test (which detects anti-Hp Immunoglobulin G) (30). The prevalence of Hp in the gastric antrum of asymptomatic subjects varies from 13% to 37% (3, 11, 26, 41-43) and seems to be age-related (13). On the contrary, we found that 59/171 (34.5%) of our Hp positive patients were symptomatic, this fact being possibly explained by both the high prevalence of documented peptic ulcer disease and the sample se- lected (i.e. subjects referred to an endoscopic unit). However, in agreement with other Authors (44), we found a close relationship between the presence of ul- cer symptoms and Hp infection: the more "dense" the presence of Hp in the gastric mucosa, the higher the prevalence of symptomatic subjects. This finding seems to be only partially related to the presence of an active ulcer: for example, only 9 out of the 26 symptomatic subjects with the highest density of Hp have an active peptic ulcer disease. In any case, Hp infected subjects were significantly more frequently seen in the active phase than in scarred phase of DU, indirectly supporting the pathogenetic role of the bac- terium on the reactivation of DU disease (20-23). H2-blockers did not affect Hp infection in our sam- ple, confirming the previous finding of both in vitro and in vivo studies (22, 31-34). In accordance with the Literature (1-12) we found that Hp- determines active gastritis, with a direct relationship between the density of the bacterium and degree of the inflammation (Table 11). Contrary to the report from Craanen and coworkers (45), intestinal metaplasia (an inhospitable site for Hp) seems to be unaffected by the infection in our sample. The preva- lence of intestinal metaplasia in our Hp-infected sub- jects was lower than that reported by Craanen (25.15% and 33.9%, respectively), while it was hi- gher in patients without Hp infection (25.21% and 15.2%), which explains the different results in the two series. In 27.5% of Hp infected subjects we iden- tified lymphoid follicles, a percentage very close to that observed by Wotherspoon and coworkers (28%) (46). 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