Diagnostics of Helicobacter pylori Infection in Patients with Peptic Ulcer Bleeding

Zusammenfassung

Hintergrund: Bei der peptischen Ulkusblutung wurde über eine insuffiziente Sensitivität von H.-pylori-Tests, insbesondere des Urease-Schnelltests (RUT), berichtet. Ziele: Validierung von RUT, Serologie und Harnstoff-Atemtest bei Patienten mit peptischer Ulkusblutung. Untersuchung des Einflusses von H.-pylori-suppressiver Behandlung (HpSuT), d. h. Antibiotika und Protonenpumpenhemmer. Patienten und Methoden: 123 konsekutive Patienten (mittleres Alter 65,5 Jahre) mit einer relevanten Blutung aus gastroduodenalen Ulzera wurden prospektiv auf eine H.-pylori-Infektion untersucht mittels direkten Tests (RUT, Histologie, Kultur und Harnstoff-Atemtest) und Serologie als indirekten Tests. Ein positiver H.-pylori-Status wurde durch positive Ergebnisse von Histologie oder Kultur definiert. Ergebnisse: Bei Patienten ohne HpSuT in den letzten vier Wochen (n = 83) lagen Sensitiviät und Spezifität des RUT bei 94 und 84 %, der Serologie bei 83 und 68 %. Die Sensitivität des Harnstoff-Atemtests sank von 82 auf 60 % nach nur einem Tag mit HpSuT. In der Gesamtgruppe erwiesen sich die Dauer der HpSuT und eine vorangehende Hospitalisation als unabhängige Faktoren für negative Resultate aller direkten Tests. Schlussfolgerungen: Bei peptischer Ulkusblutung ist der RUT kombiniert mit Histologie ein geeignetes Diagnostikum. Jedoch sollten mögliche falsch negative Ergebnisse nach kurzfristiger HpSuT oder Hospitalisation in Betracht gezogen werden. Eine nicht invasive Diagnose, basierend allein auf der Serologie, ist nicht treffsicher und sollte durch einen Harnstoff-Atemtest vor Beginn einer HpSuT ergänzt werden.

Abstract

Background: In peptic ulcer bleeding, the sensitivity of H. pylori tests, in particular of the rapid urease test (RUT), has been reported to be insufficient. Aim: To validate the RUT, serology and the urea breath test were carried out in patients with bleeding peptic ulcers, and to study the influence of H. pylori suppressive treatment (HpSuT), i. e., antibiotics and proton pump inhibitors. Patients and Methods: 123 consecutive patients (mean age 65.5 years) with a relevant bleeding from gastric or duodenal ulcers were prospectively tested for H. pylori infection by directs tests (RUT, histology, culture, urea breath test) and by IgG serology as an indirect test. Positive H. pylori status was defined by positive histology or culture. Results: In patients without HpSuT during the preceding four weeks (N = 83), the sensitivity and specificity of RUT was 94 and 84 %, that of serology 83 and 68 % respectively. The sensitivity of urea breath test decreased from 82 to 60 % after even one day of HpSuT. In the overall group, the duration of HpSuT and preceding hospitalization were independent factors linked with negative results of all direct tests. Conclusions: In peptic ulcer bleeding, RUT combined with histology is an adequate diagnostic approach. However, false negative results have to be considered following even short-term HpSuT or hospitalization. Non-invasive diagnosis based on serology alone is inaccurate and should be complemented by the urea breath test prior to starting HpSuT.

Schlüsselwörter

Helicobacter pylori - peptische Ulkusblutung - Diagnose - Urease-Schnelltest - Histologie - Kultur - Serologie - Harnstoff-Atemtest

Key words

Helicobacter pylori - peptic ulcer bleeding - diagnosis - rapid urease test - histology - culture - serology - urea breath test

References

• 1 Malfertheiner P, Megraud F, O’Morain C. et al . Current concepts in the management of Helicobacter pylori infection - the Maastricht 2 - 2000 Consensus Report.  Aliment Pharmacol Ther. 2002;  16 167-180
• 2 Van Leerdam M E, Tytgat G N. Helicobacter pylori infection in peptic ulcer haemorrhage.  Aliment Pharmacol Ther. 2002;  16 (Suppl 1) 66-78
• 3 Huang J Q, Sridhar S, Hunt R H. Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis.  Lancet. 2002;  359 14-22
• 4 Stack W A, Atherton J C, Hawkey G M. et al . Interactions between Helicobacter pylori and other risk factors for peptic ulcer bleeding.  Aliment Pharmacol Ther. 2002;  16 497-506
• 5 Castillo-Rojas G, Ballesteros M A, Ponce d L. et al . Bleeding peptic ulcers and presence of Helicobacter pylori by various tests: a case-control study.  Eur J Gastroenterol Hepatol. 2002;  14 1113-1118
• 6 Lee J M, Breslin N P, Fallon C. et al . Rapid urease tests lack sensitivity in Helicobacter pylori diagnosis when peptic ulcer disease presents with bleeding.  Am J Gastroenterol. 2000;  95 1166-1170
• 7 Feldman M, Cryer B, McArthur K E. et al . Effects of aging and gastritis on gastric acid and pepsin secretion in humans: a prospective study.  Gastroenterology. 1996;  110 1043-1052
• 8 Pilotto A, Malfertheiner P. An approach to Helicobacter pylori infection in the elderly.  Aliment Pharmacol Ther. 2002;  16 683-691
• 9 Terdiman J P, Ostroff J W. Gastrointestinal bleeding in the hospitalized patient: a case-control study to assess risk factors, causes, and outcome.  Am J Med. 1998;  104 349-354
• 10 Archimandritis A, Tzivras M, Sougioultzis S. et al . Rapid urease test is less sensitive than histology in diagnosing Helicobacter pylori infection in patients with non-variceal upper gastrointestinal bleeding.  J Gastroenterol Hepatol. 2000;  15 369-373
• 11 Colin R, Czernichow P, Baty V. et al . Low sensitivity of invasive tests for the detection of Helicobacter pylori infection in patients with bleeding ulcer.  Gastroenterol Clin Biol. 2000;  24 31-35
• 12 Griño P, Pascual S, Such J. et al . Comparison of diagnostic methods for Helicobacter pylori infection in patients with upper gastrointestinal bleeding.  Scand J Gastroenterol. 2001;  36 1254-1258
• 13 Romero G M, Vargas J, Utrilla D. et al . Estudio prospectivo sobre la influencia de la hemorragia por ulcus gastroduodenal en los métodos diagnósticos de infección por Helicobacter pylori.  Gastroenterol Hepatol. 1998;  21 267-271
• 14 Schilling D, Demel A, Adamek H E. et al . A negative rapid urease test is unreliable for exclusion of Helicobacter pylori infection during acute phase of ulcer bleeding. A prospective case control study.  Dig Liver Dis. 2003;  35 217-221
• 15 Tu T C, Lee C L, Wu C H. et al . Comparison of invasive and noninvasive tests for detecting Helicobacter pylori infection in bleeding peptic ulcers.  Gastrointest Endosc. 1999;  49 302-306
• 16 Bossuyt P M, Reitsma J B, Bruns D E. et al . The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration.  Ann Intern Med. 2003;  138 W1-12
• 17 Malfertheiner P, Jominguez-Munoz J E, Heckenmuller H. et al . Modified rapid urease test for detection of Helicobacter pylori infection.  Eur J Gastroenterol Hepatol. 1996;  8 53-56
• 18 Wolle K, Nilius M, Leodolter A. et al . Prevalence of Helicobacter pylori resistance to several antimicrobial agents in a region of Germany.  Eur J Clin Microbiol Infect Dis. 1998;  17 519-521
• 19 Leodolter A, Dominguez-Munoz J E, von Arnim U. et al . Validity of a modified 13C-urea breath test for pre- and posttreatment diagnosis of Helicobacter pylori infection in the routine clinical setting.  Am J Gastroenterol. 1999;  94 2100-2104
• 20 Megraud F, O’Morain C, Malfertheiner P. Guidelines for clinical trials in Helicobacter pylori infection. Working Party of the European Helicobacter pylori Study Group.  Gut. 1997;  41 (Suppl 2) S1-S9
• 21 Vaira D, Gatta L, Ricci C. et al . Diagnosis of Helicobacter pylori infection.  Aliment Pharmacol Ther. 2002;  16 (Suppl 1) 16-23
• 22 Vassallo J, Hale R, Ahluwalia N K. CLO vs. histology: optimal numbers and site of gastric biopsies to diagnose Helicobacter pylori.  Eur J Gastroenterol Hepatol. 2001;  13 387-390
• 23 Wildner-Christensen M, Touborg L A, Lindebjerg J. et al . Diagnosis of Helicobacter pylori in bleeding peptic ulcer patients, evaluation of urea-based tests.  Digestion. 2002;  66 9-13
• 24 Leung W K, Sung J J, Siu K L. et al . False-negative biopsy urease test in bleeding ulcers caused by the buffering effects of blood.  Am J Gastroenterol. 1998;  93 1914-1918
• 25 Houghton J, Ramamoorthy R, Pandya H. et al . Human plasma is directly bacteriocidal against Helicobacter pylori in vitro, potentially explaining the decreased detection of Helicobacter pylori during acute upper GI bleeding.  Gastrointest Endosc. 2002;  55 11-16
• 26 Lee J M, Breslin N P, Gopaul M. et al . The effects of blood on rapid urease testing for Helicobacter pylori in mucosal biopsies from the gastric antrum.  Ir J Med Sci. 2000;  169 60-62
• 27 Perry M, Vakil N, Cutler A F. Admixture with whole blood does not explain false-negative urease tests.  J Clin Gastroenterol. 2000;  30 64-65
• 28 Stoschus B, Dominguez-Munoz J E, Kalhori N. et al . Effect of omeprazole on Helicobacter pylori urease activity in vivo.  Eur J Gastroenterol Hepatol. 1996;  8 811-813
• 29 Manes G, Balzano A, Iaquinto G. et al . Accuracy of the stool antigen test in the diagnosis of Helicobacter pylori infection before treatment and in patients on omeprazole therapy.  Aliment Pharmacol Ther. 2001;  15 73-79
• 30 Laine L, Estrada R, Trujillo M. et al . Effect of proton-pump inhibitor therapy on diagnostic testing for Helicobacter pylori.  Ann Intern Med. 1998;  129 547-550
• 31 van der Voort P H, van der Hulst R W, Zandstra D F. et al . Suppression of Helicobacter pylori infection during intensive care stay: related to stress ulcer bleeding incidence?.  J Crit Care. 2001;  16 182-187
• 32 Peitz U, Leodolter A, Kahl S. et al . Antigen stool test for assessment of Helicobacter pylori infection in patients with upper gastrointestinal bleeding.  Aliment Pharmacol Ther. 2003;  17 1075-1084
• 33 Grino P, Pascual S, Such J. et al . Comparison of stool immunoassay with standard methods for detection of Helicobacter pylori infection in patients with upper-gastrointestinal bleeding of peptic origin.  Eur J Gastroenterol Hepatol. 2003;  15 525-529
• 34 López Peñas D, Naranjo R A, Muñoz Molinero J. et al . Eficacia de la determinación fecal de Helicobacter pylori mediante la técnica HpSA en enfermos con hemorragia digestiva alta.  Gastroenterol Hepatol. 2001;  24 5-8
• 35 Van Leerdam M E, van der Ende A, ten Kate F J. et al . Lack of accuracy of the noninvasive Helicobacter pylori stool antigen test in patients with gastroduodenal ulcer bleeding.  Am J Gastroenterol. 2003;  98 798-801