First regional consensus on the management of Helicobacter pylori infection in the Middle East

Table 1 Statements, level of evidence, and strength of recommendation¹

	Grading	Agreement
Chapter 1: Clinical indications and relevance of H. pylori
Statement 1	A1	100	H. pylori is a gastric pathogen. H. pylori gastritis is an infectious disease
Statement 2	A1	100	Test-and-treat is an appropriate strategy for uninvestigated dyspepsia
Statement 3	A1	100	Overall, H. pylori eradication is superior to placebo or acid suppressive therapy for long-term relief of dyspepsia; however, the magnitude of the benefit is small
Statement 4	B2	85.71	The diagnosis of H. pylori gastritis must be excluded before a reliable diagnosis of functional dyspepsia is made
Statement 5	A1	100	The use of aspirin or nonsteroidal anti-inflammatory drug increases the risk of peptic ulcer disease and its complications in patients with H. pylori infection
Statement 6	A1	85.71	H. pylori testing and treatment are advisable for high-risk patients receiving long-term aspirin therapy. H. pylori testing and treatment are advisable for treatment-naïve patients commencing long-term nonsteroidal anti-inflammatory drug therapy. Those at high-risk may require additional PPI therapy
Statement 7	A1	85.71	Long-term treatment with PPIs alters the topography of H. pylori gastritis
Statement 8	A1	100	H. pylori eradication should be considered in long-term PPI users
Statement 9	A1	100	H. pylori eradication is recommended for the management of patients with unexplained IDA, ITP, and vitamin B12 deficiency
Statement 10	A1	85.71	H. pylori eradication is the first-line treatment for localized low-grade gastric MALT lymphoma. H. pylori eradication therapy is also recommended for cases without evidence of H. pylori infection and may provide benefit even to those with advanced-stage disease
Statement 11	D2	100	H. pylori has been positively and negatively associated with extra-gastroduodenal disorders. However, the causality of these associations has not been definitively proven
Chapter 2: Diagnostic approaches and methods for H. pylori
Statement 1	A1	100	Non-invasive testing for H. pylori infection is recommended in patients with dyspepsia aged < 60 years with no specific risk and no alarming symptoms
Statement 2	B1	100	Upper GI endoscopy is required in patients with dyspepsia aged > 60 years. Functional serology may be considered a complementary diagnostic tool
Statement 3	A2	100	When endoscopy is indicated it should: (1) Apply the best available technologies; and (2) Include biopsy sampling. Biopsy samples obtained in accordance with validated protocols should result in both etiological diagnosis and gastritis staging. Any focal lesions should be additionally sampled
Statement 4	A1	100	UBT remains an important tool for diagnosing H. pylori infection before and after eradication therapy. Citric acid is an essential component of the protocol
Statement 5	A1	100	Monoclonal stool antigen test is an appropriate test before and after H. pylori treatment
Statement 6	A1	100	Molecular methods (in particular, real time-PCR, whole genome sequencing, and digital PCR) facilitate the detection of H. pylori mutations associated with resistance to clarithromycin and levofloxacin
Statement 7	A1	100	No antibiotics or bismuth should be used in the short-term post-eradication (4-6 weeks) follow-up period to permit optimum testing for H. pylori. PPIs should be stopped 14 days before testing
Statement 8	A1	85.71	Tests for serum IgG antibodies against H. pylori can serve as a screening test in specific clinical situations
Statement 9	A1	85.71	The histological assessment of atrophy should result in conclusive gastritis staging (OLGA/OLGIM), which consistently ranks the patient-specific cancer risk. Histological staging makes intestinal metaplasia subtyping clinically redundant
Chapter 3: Treatment strategies for H. pylori
Statement 1	C1	100	Antimicrobial resistance deserves high consideration in the Middle East owing to frequent improper and overuse of antibiotics
Statement 2	B1	100	Single capsule bismuth quadruple therapy is the first-line treatment recommended in areas with high (> 15%) or unknown clarithromycin resistance if individual susceptibility testing is not available. Non-bismuth concomitant quadruple therapy may be considered if bismuth is not available
Statement 3	D2	100	The treatment duration of single capsule BQT should be 10 days
Statement 4	B1	85.71	Given its proven reproducible effectiveness and lower complexity compared with sequential and hybrid therapies, concomitant therapy (PPI, amoxicillin, clarithromycin, and metronidazole administered concurrently) should be the preferred choice when selecting a non-BQT treatment strategy
Statement 5	D2	100	The recommended treatment duration of non-bismuth quadruple therapy (concomitant) is 14 days
Statement 6	B1	100	Single capsule BQT or clarithromycin-containing triple therapy may be recommended as first-line empirical treatment in areas with low clarithromycin resistance, if proven effective locally
Statement 7	B1	100	The recommended treatment duration of PPI-clarithromycin-based triple therapy is 14 days
Statement 8	C2	100	The use of high-dose PPI twice daily increases the efficacy of triple therapy. It remains unclear whether high-dose PPI administered twice daily can improve the efficacy of quadruple therapies
Statement 9	B2	85.71	Potassium-competitive acid blockers antimicrobial combination treatments are: (1) Superior or not inferior to conventional PPI-based triple therapies for first-line and second-line treatment; and (2) Superior in patients with evidence of antimicrobial resistant infections
Statement 10	D2	85.71	Empiric second-line and rescue therapies should be guided by local resistance patterns assessed by susceptibility testing and eradication rates to optimize treatment success
Statement 11	C2	100	Fluoroquinolone-containing quadruple (or triple) therapy or high-dose PPI-amoxicillin dual therapy may be recommended after the failure of single capsule BQT
Statement 12	C2	100	Single capsule BQT or a PPI-amoxicillin high-dose dual therapy are recommended as second-line treatments after the failure of PPI-clarithromycin-amoxicillin triple therapy
Statement 13	C2	85.71	Single capsule BQT or fluoroquinolone-containing quadruple (or triple) therapy may be considered after the failure of non-BQT. High-dose PPI-amoxicillin dual therapy may also be considered
Statement 14	B2	100	The use of a fluoroquinolone-containing regimen is recommended after the failure of the first-line treatment with clarithromycin-containing triple therapy or non-BQTs and second-line treatment with single capsule BQT. BQT with different antibiotics, rifabutin-containing rescue therapy, or high-dose PPI-amoxicillin dual therapy should be considered in areas with high fluoroquinolone resistance
Statement 15	B2	100	Single capsule BQT is recommended after the failure of first-line treatment with clarithromycin-containing triple therapy or non-BQTs, and second-line treatment with fluoroquinolone-containing therapy. High-dose PPI-amoxicillin dual or a rifabutin-containing regimen could be considered if single capsule BQT is not available
Statement 16	C2	85.71	The use of clarithromycin-based triple or quadruple therapy is recommended after the failure of first-line treatment with single capsule BQT and second-line treatment with fluoroquinolone-containing therapy only in areas with low clarithromycin resistance (< 15%). Otherwise, high-dose PPI-amoxicillin dual therapy, a rifabutin-containing regimen, or a combination of bismuth with different antibiotics should be used
Statement 17	C2	85.71	Single capsule BQT should be recommended as the first-line treatment in patients with proven penicillin allergy. Single capsule BQT (if not previously prescribed) and fluoroquinolone-containing regimens may represent empirical second-line rescue options
Chapter 4: H. pylori and gastric cancer prevention
Statement 1	A1	85.71	H. pylori infection plays an etiological role in a subset of adenocarcinoma of the gastroesophageal junction zone
Statement 2	A1	100	H. pylori eradication: (1) Eliminates the active inflammatory response in chronic active non-atrophic gastritis; and (2) Prevents further progression to atrophy and intestinal metaplasia in chronic non-atrophic gastritis
Statement 3	A1	100	H. pylori eradication may reverse gastric atrophy and intestinal metaplasia to some extent. It may also halt the progression of chronic atrophic gastritis to neoplastic lesions in a subset of patients
Statement 4	A1	85.71	H. pylori eradication is most effective in preventing gastric cancer before the development of severe chronic atrophic gastritis
Statement 5	A1	85.71	Diagnostic tests used to screen H. pylori infection for the purpose of gastric cancer prevention should preferably be non-invasive
Statement 6	A1	85.71	Compared with younger individuals, asymptomatic individuals aged > 60 years are considered vulnerable and at increased risk of gastric cancer
Statement 7	B1	100	Follow-up at regular intervals and the use of endoscopic biopsy protocols is mandatory in patients with severe atrophic gastritis (OLGA 3/4)
Statement 8	A1	100	Eradication of H. pylori is mandatory to reduce the risk of metachronous gastric cancer after curative endoscopic resection or gastric subtotal resection of early gastric cancer
Chapter 5: H. pylori drug resistance and the gut microbiota
Statement 1	B2	85.71	Antibiotic treatment for other reasons might select resistant H. pylori strains

¹Proton pump inhibitor, bismuth, tetracycline, and metronidazole prescribed separately is not a Food and Drug Administration-approved treatment regimen. However, Pylera^®, a combination product containing bismuth subcitrate, tetracycline, and metronidazole combined with a proton pump inhibitor for 10 days, is a Food and Drug Administration-approved treatment regimen. H. pylori: Helicobacter pylori; PPI: Proton pump inhibitor; IDA: Iron deficiency anemia; ITP: Idiopathic thrombocytopenic purpura; MALT: Mucosa-associated lymphoid tissue; OLGA/OLGIM: Operative link on gastric atrophy/operative link on gastric intestinal metaplasia; BQT: Bismuth quadruple therapy; GI: Gastrointestinal; UBT: Urea breath test.