Helicobacter pyloribismuth subsalicylate.
(See also Overview of Acid Secretion and Overview of Gastritis.)
H. pylori is a spiral-shaped, gram-negative organism that has adapted to thrive in acid. In low- and middle-income countries, it commonly causes chronic infections and is usually acquired during childhood. In the United States, infection is less common among children but increases with age: by age 60, about 50% of people are infected. Infection is most common among Black, Hispanic, and Asian people.
The organism has been cultured from stool, saliva, and dental plaque, which suggests oral-oral or fecal-oral transmission. Infections tend to cluster in families and in residents of custodial institutions. Nurses and gastroenterologists seem to be at high risk because bacteria can be transmitted by improperly disinfected endoscopes.
Pathophysiology of H. pylori Infection
Effects of H. pylori infection vary depending on the location within the stomach.
Antral-predominant infection results in increased gastrin production, probably via local impairment of somatostatin release. Resultant hypersecretion of acid predisposes to prepyloric and duodenal ulcer.
Body-predominant infection leads to gastric atrophy and decreased acid production, possibly via increased local production of interleukin-1 beta. Patients with body-predominant infection are predisposed to gastric ulcer and gastric adenocarcinoma.
Some patients have mixed infection of both antrum and body with varying clinical effects. Many patients with H. pylori infection have no noticeable clinical effects.
Ammonia produced by H. pylori enables the organism to survive in the acidic environment of the stomach and may erode the mucus barrier. Cytotoxins and mucolytic enzymes (eg, bacterial protease, lipase) produced by H. pylori may play a role in mucosal damage and subsequent ulcerogenesis.
Infected people are 3 to 6 times more likely to develop stomach cancer. H. pylori is a group 1 carcinogen (1). H. pylori infection is associated with intestinal-type adenocarcinoma of the gastric body and antrum but not cancer of the gastric cardia. Other associated cancers include gastric lymphoma and mucosa-associated lymphoid tissue (MALT) lymphoma, a monoclonally restricted B-cell tumor.
Pathophysiology reference
1. American Cancer Society: Known and probable human carcinogens. 2022. Accessed 1/20/23.
Diagnosis of H. pylori Infection
Screening of asymptomatic patients is not warranted. Tests are done during evaluation for peptic ulcer and gastritis. Posttreatment testing is typically done to confirm eradication of the organism.
Noninvasive tests
Laboratory and office-based serologic assays for antibodies to H. pylori have a sensitivity and specificity of > 85% and previously were considered the noninvasive tests of choice for initial documentation of H. pylori
>≥ 4 weeks after antibiotic therapy and 1 week after proton pump inhibitor therapy. H2 blockers do not affect the test.
Stool antigen assaysH. pylori have been developed and are available in Europe.
Invasive tests
Endoscopy is used to obtain mucosal biopsy samples for a rapid urease test (RUT) or histologic staining. Bacterial culture is of limited use because of the fastidious nature of the organism. Endoscopy is not recommended solely for diagnosis of H. pylori; noninvasive tests are preferred unless endoscopy is indicated for other reasons.
The RUT, in which presence of bacterial urease in the biopsy sample causes a color change on a special medium, is the diagnostic method of choice on tissue samples. Histologic staining of biopsy samples should be done for patients with negative RUT results but suspicious clinical findings, recent antibiotic use, or treatment with proton pump inhibitors. RUT and histologic staining each have a sensitivity and specificity of > 90%. Immunohistochemistry is routinely used in some hospital systems and adds to the value of histology because it can be used to detect a very small number of organisms.
Treatment of H. pylori Infection
Antibiotics (various regimens) plus a proton pump inhibitor
(See also the American College of Gastroenterology’s [ACG] 2017 guidelines Treatment of Helicobacter pylori Infection and the European 2022 guidelines Management of Helicobacter pylori infection: The Maastricht VI/Florence consensus report.)
Patients with complications (eg, ulcer, cancer) should have the organism eradicated. Eradication of H. pylori can even cure some cases of MALT lymphoma (but not other infection-related cancers).
Treatment of asymptomatic infection has been controversial, but the recognition of the role of H. pylori in cancer has led to a recommendation for treatment.
Vaccines, both preventive and therapeutic (ie, as an adjunct to treatment of infected patients), are under development.
H. pylori eradication requires multidrug therapy, typically antibiotics plus acid suppressants (1). Proton pump inhibitors suppress H. pylori, and the increased gastric pH accompanying their use can enhance tissue concentration and efficacy of antimicrobials, creating a hostile environment for H. pylori.
Quadruple therapy is the best initial therapy in areas where the clarithromycin resistance rate is > 15% and is recommended in both the European guidelines (2) and in the ACG guidelines (3). In quadruple therapy, the following oral medications are given for 14 days (4):
In regions where H. pylori clarithromycin resistance is known to be < 15% and in patients with no previous history of macrolide exposure, triple therapy with the following oral medications for 14 days remains an initial treatment option (2, 3):
or
amoxicillin, and a fluoroquinolone (2amoxicillin, and a PPI is an alternative (5). For multidrug-resistant strains of H. pylori, triple therapy with a PPI, rifabutin, and amoxicillin seems to be effective (6).
The ACG guidelines recommend that triple therapy with clarithromycin not be used if quadruple therapy fails (3).
The European guidelines suggest double or triple therapy with a potassium-competitive acid inhibitor may be superior or noninferior to standard triple therapy (2, 7).
H. pylori infection (eg, bleeding ulcer). Recurrent bleeding ulcer is likely if the infection is not eradicated.
If either quadruple or triple therapy fails to eradicate H. pylori8).
Treatment references
1. Yang JC, Lin CJ, Wang HL, et al: High-dose dual therapy is superior to standard first-line or rescue therapy for Helicobacter pylori infection. Clin Gastroenterol Hepatol 13(5):895–905.e5, 2015. doi: 10.1016/j.cgh.2014.10.036
2. Malfertheiner P, Megraud F, Rokkas T, et al: Management of Helicobacter pylori infection: The Maastricht VI/Florence consensus report. Gut gutjnl-2022-327745, 2022. doi: 10.1136/gutjnl-2022-327745
3. Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG clinical guideline: Treatment of Helicobacter pylori infection. Am J Gastroenterol 112(2):212–239, 2017. doi: 10.1038/ajg.2016.563. Clarification and additional information. Am J Gastroenterol 113(7):1102, 2018. doi: 10.1038/s41395-018-0132-6
4. Fallone CA, Chiba N, van Zanten SV, et al: The Toronto consensus for the treatment of Helicobacter pylori infection in adults. Gastroenterology 151(1):51–69, 2016. doi: 10.1053/j.gastro.2016.04.006
5. Graham DY, Canaan Y, Maher J, et al: Rifabutin-based triple therapy (RHB-105) for Helicobacter pylori eradication: A double-blind, randomized, controlled trial. Ann Intern Med 172(12):795–802, 2020. doi: 10.7326/M19-3734
6. Fiorini G, Zullo A, Vakil N, et alHelicobacter pylori. J Clin Gastroenterol 52(2):137–140, 2018. doi: 10.1097/MCG.0000000000000540
7. Chey WD, Mégraud F, Laine L, et al: Vonoprazan triple and dual therapy for Helicobacter pylori infection in the United States and Europe: Randomized clinical trial. Gastroenterology 163(3):608–619, 2022. doi: 10.1053/j.gastro.2022.05.055
8. Shah SC, Iyer PG, Moss SF: AGA clinical practice update on the management of refractory Helicobacter pylori infection: Expert review. Gastroenterology 160(5):1831–1841, 2021. doi: 10.1053/j.gastro.2020.11.059
Key Points
H. pylori is a gram-negative organism that is highly adapted to an acid environment and often infects the stomach; incidence of infection increases with age—by age 60, about 50% of people are infected.
Infection predisposes to gastric, prepyloric, and duodenal ulcers and increases risk of gastric adenocarcinoma and lymphoma.
More Information
The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
American College of Gastroenterology: Guidelines for the treatment of Helicobacter pylori infection (2017)
Maastricht VI/Florence consensus report: Management of Helicobacter pylori infection (2022)
