- Email: [email protected]
Relationship between interleukin-1β mRNA level in gastric fundic mucosa and gastric juice pH in patients infected with Helicobacter pylori
April 1998
Esophageal, Gastric, and Duodenal Disorders A225
When GC were considered according to age the prevalence of CagA in HP+ve was 97/125(78%) vs 248/375(66%) in older and younger than 60 years respectively. Table 2: multivariate analysis comparing patients with DU or GU vs NUD (OR adjusted for age and sex) according to HP and CagA. NUD DU GU N (%) N (%) OR N (%) OR H pylori+ve/CagA-ve 290 (23) 56 (20) 3.5 11 (15) 1.1 H pylori+ve/CagA+ve 528 (41) 194 (70) 6.7 48 (68) 2.9 CONCLUSIONS: -1 CagA, though associated with more severe diseases, (DU 78%, GU 81% and GC 69% respectively) did not reach the high prevalence generally reported; -2 Infection by CagA +ve HP increased the risk of DU and, to a lesser extent, of GU compared to infection by CagA -ve HP (OR 6.7 vs 3.5 and 2.9 vs 1.1 for CagA +ve vs CagA -ve DU and GU respectively). • G0921 PREVALENCE OF HELICOBACTER PYLORI (ItP) CagA: CROSSSECTIONAL STUDY IN 1452 PATIENTS THROUGH ITALY. M Menegatti. D Palli, M Miglioli, C Saieva, D Vaira & The Italian Helicobacter pylori Study Group. 1st Medical Clinic Bologna, Epidemiology Unit CSPO Florence, Italy. Recent studies reported that the prevalence of CagA +ve strains varies among countries and even region. We investigate the prevalence of CagA and its correlation to gastroduodenal pathology. METHODS: We previously assessed the prevalence of HP in patients undergoing their first endoscopy through Italy. Of the 3281 patients enrolled 1452 (44.3%) serum samples were still available and are the object of present analysis. Patients underwent endoscopy with biopsies (histology by H & E and Giemsa) and a blood sample was collected for serology. Anti-HP IgG were assessed by ELISA (Helori test, Eurospital, Trieste, Italy) (sensitivity and specificity of 94% and 87% respectively). Anti-CagA was evaluated by ELISA (Helori CTX, Eurospital, Trieste, Italy) with purified CagA as antigen (sensitivity and specificity of 96% and 90% respectively compared to Western Blotting and RIBA -RIBATM SIA- Chiron Corporation, Emeryville, California, USA). Study participants were classified according to sex, age, scholarity, endoscopic diagnosis, anti-HP and -CagA reactivity. Logistic models were used for multivariate analysis of association between HP and -CagA positivity and other factors and adjusted odds ratios (OR) were estimated. RESULTS: 76 subjects had border-line CagA results and were excluded. Table 1: prevalence of CagA in HP +ve patients CagA Normal Gastritis Duodenal Gastric Mucosa Ulcer Ulcer HP+ve H P + v e H P + v e H P + v e +ve 117(56) 322(59) 171(85) 41(80) -ve 93 (44) 219 (40) 30 (15) 10 (20) Total 210(20) 541(52) 201(19) 51(5)
according Gastric Cancer HP+ve 6(86) 1 (14) 7(1)
to endos Other Disease HP+ve 14(52) 13 (48) 27(3)
Total HP+ve 671(65) 366 (35) 1037(100)
Table 2: association of endoscopic findings with HP or CagA positivity: multivariate analysis [OR (adjusted for age, sex and education; due to small number gastric cancers were combined into the "other' group).] ENDOSCOPY N° liP ve % [OR(CI95%)] CagA+ve [OR(CI95%)] 38.9 [1] Normal mucosa 342 61.4 [1] 48.3 [1.4(1.1-1.8)] Gastritis-duodenitis 712 76.0 [1.7 (1.3-3.9)] 74.1 {4.0(2.1-7.6)] Gastric ulcer 58 87.9 [ 3.1 (1.3-7.2)] 84.1 [7.8(5.1-12.1)] Duodenal ulcer 214 93.9 [8.8 (4.7-16.2)] 44.0 [1.1 (0.¢2.1)] Other 50 68 [0.9 (0.5-1.8)] 52.5 Total 1376 75.4 CONCLUSION: In this large unselected series of patients undergoing their first endoscopy through Italy the prevalence of CagA ranged from 39-to 84%. Patients with HP and/or CagA positivity were, without any differences, at increased risk of developing duodenal and gastric ulcer. This study was supported by Eurospital, Trieste, Italy • G0922 USEFULNESS OF ADDING THE DETERMINATION OF HELICOBACTER PYLORI (HP)-CagA TO A PRE-ENDOSCOPIC SCREENING POLICY. M Meneoatti. D Vaira, D Palli, G. Masala, M Miglioli & The Italian Helicobacter pylori Study Group. 1st Medical Clinic Bologna, Epidemiology Unit & IST Sect. CSPO, Florence, Italy.
HP determination, together with age, NSAIDs use and presence of alarm symptoms, has been proposed as a preendoscopic screening: young HP negative patients without alarm symptoms or NSAIDs intake could safely avoid endoscopy, thus reducing endoscopic workload and medical costs. This approach, however could have relevant drawbacks because a proportion of diagnoses could be missed. It is not clear whether determination of CagA, as an additional marker of increased risk, could improve the performance of such a screening. We evaluated the reliability of HP alone compared to HP and CagA determination in two age groups. METHODS: We previously assessed
the prevalence of HP in patients undergoing their first endoscopy through Italy. Of the 3281 patients enrolled 1452 (44.3%) serum samples were still available and are the object of the present analysis. Anti-HP IgG were assessed by ELISA (Helori test, Eurospital, Trieste, Italy) (sensitivity and specificity 94% and 87% respectively). Anti-CagA was evaluated by ELISA (Helori CTX, Eurospital, Trieste, Italy) with purified CagA (sensitivity and specificity 96 and 90% respectively). After determining the prevalence of HP and -CagA patients were divided into two age groups, below or over 45 years, and: workload reduction, false negative rate and negative predictive value were estimated. RESULTS: 76 sera had borderline CagA results and were excluded thus leaving 1376 patients for analysis (M/F 758/618, mean age 48 yrs). In Table: endoscopic findings according to age and HP/CagA serology (NUD=non ulcer dyspepsia). NUD
CagA+ve
H~+ve(%) CagA+ve
Hp-ve( % ) CagA-ve Hp+ve(%'~ CagA-ve np-ve(%) Total
<45 yrs 150 (33) 21 (5) 105 (23) 182 (40); 458 (81)
>45 yrs 303 (47) 18 (3) 220 (34) 97 (15) 638 (79),
Duodenal Gastric Cancer Ulcer <45 >45 <45 >45 yrs yrs yes yrs 80 91 6 (90) (73) (76) 4 5 1 (4) (4) (12) 5 25 1 (6) (20) (12) 4 O) 89 125 8 (1) (16) (15)
Gastric Ulcer <45 >45 yrs yes 10 31 (59) (76) 1 1 (6) (2) 3 7 (18) (17) 3 2 (18) (5) 17 41 (3) (5)
Total <45 yrs 240 (43) 26 (5) 113 (20) 185 03) 564 (100)
>45 yrs 431 (53) 25 (3) 253 (31) 103 (13) 812 (100)
CONCLUSION: A preendoscopic screening for HP and CagA would have resulted in one-third (185/564) reduction of workload, a low false negative rate (3%: 3 gastric ulcers out of 106 total ulcers: 17 gastric + 89 duodenal) and a very high negative predictive value (182/185; 98%) in younger, but not older patients. The use of HP determination alone was confirmed as less reliable. This study was supported by Eurospital, Trieste, Italy G0923 RELATIONSHIP BETWEEN INTERLEUKIN-113 mRNA LEVEL IN GASTRIC FUNDIC MUCOSA AND GASTRIC JUICE pH IN PATIENTS INFECTED WITH HELICOBACTER PYLORL Wang Mengchunl,2), Takahisa Furuta2), Misako Takashima2), Hajime Futami 2), Hiroyuki Hanai 2), Eizo Kaneko2). ODepartment of Internal Medicine, Chinese Medical College, Sheng yang, China, and 2)First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
Backerounds/Aims: The effects of Helicobacter pylori (Hp) infection on gastric acid secretion have not been clearly determined. The aim of this study was to determined the effect of Hp infection on the relationship between gastric juice pH and expression of the gene for interleukin-113 (IL-113), which is reported to inhibit gastric acid secretion. Methods: Gastric juice pH and serum gastrin levels were measured in 15 patients with peptic ulcer disease and Hp infection, who were treated with lansoprazole and amoxicillin and/or clarithromycin. Before and one month after treatment, gastroduodenoscopy was performed and several biopsy specimens were obtained from fundic gland mucosa. Serum gastrin levels were measured by radioimmunoassay (RIA). Total RNA was extracted from fundic gland biopsy specimens, and the amount of IL-113 mRNA in gastric fundic gland mucosa was measured by a competitive RT-PCR method. These parameters were determined before and after treatment. H. pylori infection was diagnosed on the basis of results of culture, rapid urease test (RUT), histology, PCR, and [13C]urea breath test as previously reported (Furuta T, et al. J Clin Microbiol 1996; 34: 2421-5). Results: Before treatment, a significant positive correlation was observed between IL-l[3 mRNA level and gastric juice pH (Fig). After treatment, significant decreases in IL-113 mRNA level, gastric juice pH, and serum gastrin levels were observed in patients with eradication of Hp, while no significant changes in any of these parameters were observed in patients without eradication. Conclusions: These findings suggest that Hp infection induces acid inhibitory cytokines such as IL-113 and suppresses acid secretion, resulting in increases in gastric juice pH and serum gastrin levels. Eradication of Hp decreases IL-113 induction, with increase in gastric juice acidity and normalization of serum gastrin levels. 8,C 7.C
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This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education of Japan (10010414).
Esophageal, Gastric, and Duodenal Disorders A225
When GC were considered according to age the prevalence of CagA in HP+ve was 97/125(78%) vs 248/375(66%) in older and younger than 60 years respectively. Table 2: multivariate analysis comparing patients with DU or GU vs NUD (OR adjusted for age and sex) according to HP and CagA. NUD DU GU N (%) N (%) OR N (%) OR H pylori+ve/CagA-ve 290 (23) 56 (20) 3.5 11 (15) 1.1 H pylori+ve/CagA+ve 528 (41) 194 (70) 6.7 48 (68) 2.9 CONCLUSIONS: -1 CagA, though associated with more severe diseases, (DU 78%, GU 81% and GC 69% respectively) did not reach the high prevalence generally reported; -2 Infection by CagA +ve HP increased the risk of DU and, to a lesser extent, of GU compared to infection by CagA -ve HP (OR 6.7 vs 3.5 and 2.9 vs 1.1 for CagA +ve vs CagA -ve DU and GU respectively). • G0921 PREVALENCE OF HELICOBACTER PYLORI (ItP) CagA: CROSSSECTIONAL STUDY IN 1452 PATIENTS THROUGH ITALY. M Menegatti. D Palli, M Miglioli, C Saieva, D Vaira & The Italian Helicobacter pylori Study Group. 1st Medical Clinic Bologna, Epidemiology Unit CSPO Florence, Italy. Recent studies reported that the prevalence of CagA +ve strains varies among countries and even region. We investigate the prevalence of CagA and its correlation to gastroduodenal pathology. METHODS: We previously assessed the prevalence of HP in patients undergoing their first endoscopy through Italy. Of the 3281 patients enrolled 1452 (44.3%) serum samples were still available and are the object of present analysis. Patients underwent endoscopy with biopsies (histology by H & E and Giemsa) and a blood sample was collected for serology. Anti-HP IgG were assessed by ELISA (Helori test, Eurospital, Trieste, Italy) (sensitivity and specificity of 94% and 87% respectively). Anti-CagA was evaluated by ELISA (Helori CTX, Eurospital, Trieste, Italy) with purified CagA as antigen (sensitivity and specificity of 96% and 90% respectively compared to Western Blotting and RIBA -RIBATM SIA- Chiron Corporation, Emeryville, California, USA). Study participants were classified according to sex, age, scholarity, endoscopic diagnosis, anti-HP and -CagA reactivity. Logistic models were used for multivariate analysis of association between HP and -CagA positivity and other factors and adjusted odds ratios (OR) were estimated. RESULTS: 76 subjects had border-line CagA results and were excluded. Table 1: prevalence of CagA in HP +ve patients CagA Normal Gastritis Duodenal Gastric Mucosa Ulcer Ulcer HP+ve H P + v e H P + v e H P + v e +ve 117(56) 322(59) 171(85) 41(80) -ve 93 (44) 219 (40) 30 (15) 10 (20) Total 210(20) 541(52) 201(19) 51(5)
according Gastric Cancer HP+ve 6(86) 1 (14) 7(1)
to endos Other Disease HP+ve 14(52) 13 (48) 27(3)
Total HP+ve 671(65) 366 (35) 1037(100)
Table 2: association of endoscopic findings with HP or CagA positivity: multivariate analysis [OR (adjusted for age, sex and education; due to small number gastric cancers were combined into the "other' group).] ENDOSCOPY N° liP ve % [OR(CI95%)] CagA+ve [OR(CI95%)] 38.9 [1] Normal mucosa 342 61.4 [1] 48.3 [1.4(1.1-1.8)] Gastritis-duodenitis 712 76.0 [1.7 (1.3-3.9)] 74.1 {4.0(2.1-7.6)] Gastric ulcer 58 87.9 [ 3.1 (1.3-7.2)] 84.1 [7.8(5.1-12.1)] Duodenal ulcer 214 93.9 [8.8 (4.7-16.2)] 44.0 [1.1 (0.¢2.1)] Other 50 68 [0.9 (0.5-1.8)] 52.5 Total 1376 75.4 CONCLUSION: In this large unselected series of patients undergoing their first endoscopy through Italy the prevalence of CagA ranged from 39-to 84%. Patients with HP and/or CagA positivity were, without any differences, at increased risk of developing duodenal and gastric ulcer. This study was supported by Eurospital, Trieste, Italy • G0922 USEFULNESS OF ADDING THE DETERMINATION OF HELICOBACTER PYLORI (HP)-CagA TO A PRE-ENDOSCOPIC SCREENING POLICY. M Meneoatti. D Vaira, D Palli, G. Masala, M Miglioli & The Italian Helicobacter pylori Study Group. 1st Medical Clinic Bologna, Epidemiology Unit & IST Sect. CSPO, Florence, Italy.
HP determination, together with age, NSAIDs use and presence of alarm symptoms, has been proposed as a preendoscopic screening: young HP negative patients without alarm symptoms or NSAIDs intake could safely avoid endoscopy, thus reducing endoscopic workload and medical costs. This approach, however could have relevant drawbacks because a proportion of diagnoses could be missed. It is not clear whether determination of CagA, as an additional marker of increased risk, could improve the performance of such a screening. We evaluated the reliability of HP alone compared to HP and CagA determination in two age groups. METHODS: We previously assessed
the prevalence of HP in patients undergoing their first endoscopy through Italy. Of the 3281 patients enrolled 1452 (44.3%) serum samples were still available and are the object of the present analysis. Anti-HP IgG were assessed by ELISA (Helori test, Eurospital, Trieste, Italy) (sensitivity and specificity 94% and 87% respectively). Anti-CagA was evaluated by ELISA (Helori CTX, Eurospital, Trieste, Italy) with purified CagA (sensitivity and specificity 96 and 90% respectively). After determining the prevalence of HP and -CagA patients were divided into two age groups, below or over 45 years, and: workload reduction, false negative rate and negative predictive value were estimated. RESULTS: 76 sera had borderline CagA results and were excluded thus leaving 1376 patients for analysis (M/F 758/618, mean age 48 yrs). In Table: endoscopic findings according to age and HP/CagA serology (NUD=non ulcer dyspepsia). NUD
CagA+ve
H~+ve(%) CagA+ve
Hp-ve( % ) CagA-ve Hp+ve(%'~ CagA-ve np-ve(%) Total
<45 yrs 150 (33) 21 (5) 105 (23) 182 (40); 458 (81)
>45 yrs 303 (47) 18 (3) 220 (34) 97 (15) 638 (79),
Duodenal Gastric Cancer Ulcer <45 >45 <45 >45 yrs yrs yes yrs 80 91 6 (90) (73) (76) 4 5 1 (4) (4) (12) 5 25 1 (6) (20) (12) 4 O) 89 125 8 (1) (16) (15)
Gastric Ulcer <45 >45 yrs yes 10 31 (59) (76) 1 1 (6) (2) 3 7 (18) (17) 3 2 (18) (5) 17 41 (3) (5)
Total <45 yrs 240 (43) 26 (5) 113 (20) 185 03) 564 (100)
>45 yrs 431 (53) 25 (3) 253 (31) 103 (13) 812 (100)
CONCLUSION: A preendoscopic screening for HP and CagA would have resulted in one-third (185/564) reduction of workload, a low false negative rate (3%: 3 gastric ulcers out of 106 total ulcers: 17 gastric + 89 duodenal) and a very high negative predictive value (182/185; 98%) in younger, but not older patients. The use of HP determination alone was confirmed as less reliable. This study was supported by Eurospital, Trieste, Italy G0923 RELATIONSHIP BETWEEN INTERLEUKIN-113 mRNA LEVEL IN GASTRIC FUNDIC MUCOSA AND GASTRIC JUICE pH IN PATIENTS INFECTED WITH HELICOBACTER PYLORL Wang Mengchunl,2), Takahisa Furuta2), Misako Takashima2), Hajime Futami 2), Hiroyuki Hanai 2), Eizo Kaneko2). ODepartment of Internal Medicine, Chinese Medical College, Sheng yang, China, and 2)First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
Backerounds/Aims: The effects of Helicobacter pylori (Hp) infection on gastric acid secretion have not been clearly determined. The aim of this study was to determined the effect of Hp infection on the relationship between gastric juice pH and expression of the gene for interleukin-113 (IL-113), which is reported to inhibit gastric acid secretion. Methods: Gastric juice pH and serum gastrin levels were measured in 15 patients with peptic ulcer disease and Hp infection, who were treated with lansoprazole and amoxicillin and/or clarithromycin. Before and one month after treatment, gastroduodenoscopy was performed and several biopsy specimens were obtained from fundic gland mucosa. Serum gastrin levels were measured by radioimmunoassay (RIA). Total RNA was extracted from fundic gland biopsy specimens, and the amount of IL-113 mRNA in gastric fundic gland mucosa was measured by a competitive RT-PCR method. These parameters were determined before and after treatment. H. pylori infection was diagnosed on the basis of results of culture, rapid urease test (RUT), histology, PCR, and [13C]urea breath test as previously reported (Furuta T, et al. J Clin Microbiol 1996; 34: 2421-5). Results: Before treatment, a significant positive correlation was observed between IL-l[3 mRNA level and gastric juice pH (Fig). After treatment, significant decreases in IL-113 mRNA level, gastric juice pH, and serum gastrin levels were observed in patients with eradication of Hp, while no significant changes in any of these parameters were observed in patients without eradication. Conclusions: These findings suggest that Hp infection induces acid inhibitory cytokines such as IL-113 and suppresses acid secretion, resulting in increases in gastric juice pH and serum gastrin levels. Eradication of Hp decreases IL-113 induction, with increase in gastric juice acidity and normalization of serum gastrin levels. 8,C 7.C
.~
r,,O.S53, p~O.05 o .0.654, p(O.(15
Q
•
•
S,( 4.C
2
4
6
8
10
12
14
111 18
20
This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education of Japan (10010414).