Achlorhydria
- Overview
- Theory
- Diagnosis
- Management
- Follow up
- Resources
Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
all patients
Helicobacter pylori testing
Because Helicobacter pylori, an infection considered carcinogenic by the World Health Organization, plays a role in the pathogenesis of most cases of atrophic gastritis, it is reasonable to test for the organism and, if present, eradicate it.[39]Busuttil RA, Boussioutas A. Intestinal metaplasia: a premalignant lesion involved in gastric carcinogenesis. J Gastroenterol Hepatol. 2009 Feb;24(2):193-201. http://www.ncbi.nlm.nih.gov/pubmed/19215332?tool=bestpractice.com [67]Gupta S, Li D, El Serag HB, et al. AGA clinical practice guidelines on management of gastric intestinal metaplasia. Gastroenterology. 2020 Feb;158(3):693-702. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340330 http://www.ncbi.nlm.nih.gov/pubmed/31816298?tool=bestpractice.com
Gastric atrophy in the oxyntic mucosa (fundus and corpus), but not necessarily intestinal metaplasia, may improve when re-examined 10 years after H pylori eradication.[124]Toyokawa T, Suwaki K, Miyake Y, et al. Eradication of Helicobacter pylori infection improved gastric mucosal atrophy and prevented progression of intestinal metaplasia, especially in the elderly population: a long-term prospective cohort study. J Gastroenterol Hepatol. 2010 Mar;25(3):544-7. http://www.ncbi.nlm.nih.gov/pubmed/19817964?tool=bestpractice.com However, these findings are controversial.[88]Hwang YJ, Kim N, Lee HS, et al. Reversibility of atrophic gastritis and intestinal metaplasia after Helicobacter pylori eradication - a prospective study for up to 10 years. Aliment Pharmacol Ther. 2018 Feb;47(3):380-90. http://www.ncbi.nlm.nih.gov/pubmed/29193217?tool=bestpractice.com [89]Choi IJ, Kook MC, Kim YI, et al. Helicobacter pylori therapy for the prevention of metachronous gastric cancer. N Engl J Med. 2018 Mar 22;378(12):1085-95. https://www.nejm.org/doi/10.1056/NEJMoa1708423?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0www.ncbi.nlm.nih.gov http://www.ncbi.nlm.nih.gov/pubmed/29562147?tool=bestpractice.com [125]De Vries AC, Kuipers EJ, Rauws EA. Helicobacter pylori eradication and gastric cancer: when is the horse out of the barn? Am J Gastroenterol. 2009 Jun;104(6):1342-5. http://www.ncbi.nlm.nih.gov/pubmed/19491846?tool=bestpractice.com
Helicobacter pylori eradication therapy
Treatment recommended for ALL patients in selected patient group
The American College of Gastroenterology (ACG) recommends empiric first-line regimens for treatment-naive patients with H pylori infection.[92]Chey WD, Howden CW, Moss SF, et al. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2024 Sep 1;119(9):1730-53. https://journals.lww.com/ajg/fulltext/2024/09000/acg_clinical_guideline__treatment_of_helicobacter.13.aspx http://www.ncbi.nlm.nih.gov/pubmed/39626064?tool=bestpractice.com
Optimized bismuth quadruple therapy, consisting of a standard-dose proton-pump inhibitor (PPI) plus bismuth plus tetracycline plus metronidazole for 14 days, is the preferred first-line regimen when antibiotic susceptibility is unknown. This regimen may be used in patients with or without a penicillin allergy.[92]Chey WD, Howden CW, Moss SF, et al. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2024 Sep 1;119(9):1730-53. https://journals.lww.com/ajg/fulltext/2024/09000/acg_clinical_guideline__treatment_of_helicobacter.13.aspx http://www.ncbi.nlm.nih.gov/pubmed/39626064?tool=bestpractice.com
Other regimens that can be considered first-line for patients with no penicillin allergy include: rifabutin triple therapy (omeprazole plus amoxicillin plus rifabutin) for 14 days; or potassium-competitive acid blocker dual therapy (vonoprazan plus amoxicillin) for 14 days. Potassium-competitive acid blocker triple therapy (vonoprazan plus clarithromycin plus amoxicillin) is another option, but should be avoided in patients with previous exposure to macrolide antibiotics.[92]Chey WD, Howden CW, Moss SF, et al. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2024 Sep 1;119(9):1730-53. https://journals.lww.com/ajg/fulltext/2024/09000/acg_clinical_guideline__treatment_of_helicobacter.13.aspx http://www.ncbi.nlm.nih.gov/pubmed/39626064?tool=bestpractice.com [127]National Institute for Health and Care Excellence. Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management. Oct 2019 [internet publiction]. https://www.nice.org.uk/guidance/cg184
European guidelines also recommend bismuth quadruple therapy as initial treatment in both areas with clarithromycin resistance rates greater or less than 15%. If this treatment fails, the European guidelines recommend different alternative regimens to the US guidelines. Other options may include levofloxacin triple or quadruple therapy, or clarithromycin triple or quadruple therapy. Choice of the specific regimen depends on the level of clarithromycin resistance and you should consult your local guidelines for options. Fourteen days of treatment are recommended.[91]Malfertheiner P, Megraud F, Rokkas T, et al. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut. 2022 Aug 8. https://pmc.ncbi.nlm.nih.gov/articles/PMC9422802 http://www.ncbi.nlm.nih.gov/pubmed/35944925?tool=bestpractice.com
All regimens contain antibiotics and therefore may cause diarrhea, promote opportunistic infections, and interfere with absorption of many other drugs, including oral contraceptives.
Check for eradication of H pylori at least 1 month after the end of therapy with an appropriately conducted urea breath test, fecal antigen test, or biopsy-based test.[91]Malfertheiner P, Megraud F, Rokkas T, et al. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut. 2022 Aug 8. https://pmc.ncbi.nlm.nih.gov/articles/PMC9422802 http://www.ncbi.nlm.nih.gov/pubmed/35944925?tool=bestpractice.com [92]Chey WD, Howden CW, Moss SF, et al. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2024 Sep 1;119(9):1730-53. https://journals.lww.com/ajg/fulltext/2024/09000/acg_clinical_guideline__treatment_of_helicobacter.13.aspx http://www.ncbi.nlm.nih.gov/pubmed/39626064?tool=bestpractice.com
To optimize the management of H pylori infection, eradication therapy should be based on patterns of local and individual antimicrobial resistance.[133]Fallone CA, Moss SF, Malfertheiner P. Reconciliation of recent Helicobacter pylori treatment guidelines in a time of increasing resistance to antibiotics. Gastroenterology. 2019 Jul;157(1):44-53. http://www.ncbi.nlm.nih.gov/pubmed/30998990?tool=bestpractice.com [134]Flores-Treviño S, Mendoza-Olazarán S, Bocanegra-Ibarias P, et al. Helicobacter pylori drug resistance: therapy changes and challenges. Expert Rev Gastroenterol Hepatol. 2018 Aug;12(8):819-27. http://www.ncbi.nlm.nih.gov/pubmed/29976092?tool=bestpractice.com Next-generation sequencing on gastric biopsies to determine antimicrobial susceptibility has been shown to increase the likelihood of successful treatment compared to conventional empirical therapy.[135]Cummings LC, Hojat LS, Nguyen DC, et al. Tailored treatment based on helicobacter pylori genetic markers of resistance is associated with higher eradication success. Am J Gastroenterol. 2023 Feb 1;118(2):360-3. https://pmc.ncbi.nlm.nih.gov/articles/PMC9889191 http://www.ncbi.nlm.nih.gov/pubmed/36574274?tool=bestpractice.com However, H pylori culture and molecular testing is not widely available in all countries.[136]Park CS, Lee SM, Park CH, et al. Pretreatment antimicrobial susceptibility-guided vs. clarithromycin-based triple therapy for Helicobacter pylori eradication in a region with high rates of multiple drug resistance. Am J Gastroenterol. 2014 Oct;109(10):1595-602. http://www.ncbi.nlm.nih.gov/pubmed/25091062?tool=bestpractice.com
Examples of eradication regimens (based on ACG guidelines) are provided here. Specific regimens may be available as proprietary combination formulations. However, local guidelines should be consulted to aid selection of an appropriate regimen and determine treatment courses.
If the first treatment fails, at least one alternative regimen should be tried. Second-line regimens should avoid the antibiotics that were given in the first-line regimen.[127]National Institute for Health and Care Excellence. Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management. Oct 2019 [internet publiction]. https://www.nice.org.uk/guidance/cg184 [132]Chey WD, Leontiadis GI, Howden CW, et al. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2017 Feb;112(2):212-39. https://journals.lww.com/ajg/Fulltext/2017/02000/ACG_Clinical_Guideline__Treatment_of_Helicobacter.12.aspx http://www.ncbi.nlm.nih.gov/pubmed/28071659?tool=bestpractice.com
In patients who have persistent H pylori infection despite receiving a previous course of eradication therapy, any subsequent treatment is considered second-line (or third-line if they have had two previous courses).[92]Chey WD, Howden CW, Moss SF, et al. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2024 Sep 1;119(9):1730-53. https://journals.lww.com/ajg/fulltext/2024/09000/acg_clinical_guideline__treatment_of_helicobacter.13.aspx http://www.ncbi.nlm.nih.gov/pubmed/39626064?tool=bestpractice.com Choice of regimen will depend on previous treatments. The ACG provides guidance on suggested regimens and it would also be advisable to consult local guidance.[92]Chey WD, Howden CW, Moss SF, et al. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2024 Sep 1;119(9):1730-53. https://journals.lww.com/ajg/fulltext/2024/09000/acg_clinical_guideline__treatment_of_helicobacter.13.aspx http://www.ncbi.nlm.nih.gov/pubmed/39626064?tool=bestpractice.com
Primary options
Bismuth quadruple therapy
omeprazole: 20 mg orally twice daily
or
lansoprazole: 30 mg orally twice daily
or
rabeprazole: 20 mg orally twice daily
or
esomeprazole: 20 mg orally twice daily
-- AND --
bismuth subsalicylate: 300 mg orally four times daily
More bismuth subsalicylateBismuth subsalicylate is available in a proprietary combination formulation with metronidazole and tetracycline in some countries. Bismuth is also available as the bismuth subcitrate salt, which may also be available in a proprietary combination formulation with metronidazole and tetracycline in some countries. The dose differs between bismuth salts. Consult your local drug information source for more information.
-- AND --
metronidazole: 500 mg orally three to four times daily
-- AND --
tetracycline: 500 mg orally four times daily
OR
Rifabutin triple therapy (treatment-naive)
omeprazole/amoxicillin/rifabutin: (10 mg omeprazole/250 mg amoxicillin/12.5 mg rifabutin per capsule) 4 capsules orally three times daily
OR
Potassium-competitive acid blocker (PCAB) dual therapy
vonoprazan and amoxicillin: 20 mg (vonoprazan) orally twice daily and 1000 mg (amoxicillin) orally three times daily
OR
Potassium-competitive acid blocker (PCAB) triple therapy
vonoprazan and amoxicillin and clarithromycin: 20 mg (vonoprazan) orally twice daily and 1000 mg (amoxicillin) orally twice daily and 500 mg (clarithromycin) orally twice daily
parenteral vitamin B12
Treatment recommended for ALL patients in selected patient group
Cobalamin deficiency can be treated with intramuscular cyanocobalamin (vitamin B12).
Primary options
cyanocobalamin (vitamin B12): 1000 micrograms intramuscularly once daily or on alternate days for 1 week, followed by 1000 micrograms once weekly for 4-8 weeks, followed by 1000 micrograms once monthly
iron replacement therapy
Treatment recommended for ALL patients in selected patient group
Oral iron is used to treat iron deficiency.
Traditionally, oral ferrous sulfate is prescribed; there is evidence to suggest that once daily or alternate daily dosing regimens may optimize iron absorption and decrease adverse effects compared with standard regimens.[137]Stoffel NU, Cercamondi CI, Brittenham G, et al. Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials. Lancet Haematol. 2017 Nov;4(11):e524-33. http://www.ncbi.nlm.nih.gov/pubmed/29032957?tool=bestpractice.com
Oral iron is sometimes coformulated with ascorbic acid (vitamin C). Reducing substances such as ascorbic acid promotes the conversion of Fe3+ to Fe2+, thereby improving solubility and absorption.
Parenteral iron can be given intramuscularly but intravenously is the preferred method.[143]Fishbane S, Ungureanu VD, Maeska JK, et al. The safety of intravenous iron dextran in hemodialysis patients. Am J Kidney Dis. 1996 Oct;28(4):529-34. http://www.ncbi.nlm.nih.gov/pubmed/8840942?tool=bestpractice.com [144]Faich G, Strobos J. Sodium ferric gluconate complex in sucrose: safer intravenous iron therapy than iron dextrans. Am J Kidney Dis. 1999 Mar;33(3):464-70. http://www.ncbi.nlm.nih.gov/pubmed/10070910?tool=bestpractice.com The iron deficit is calculated based on the premise that 1 g of hemoglobin contains 3.3 mg of elemental iron.
Primary options
ferrous sulfate: 65-130 mg orally once daily or on alternate days or three times weekly
More ferrous sulfateDose expressed as elemental iron: 65 mg elemental iron = 325 mg ferrous sulfate.
Secondary options
sodium ferric gluconate complex: consult specialist for guidance on dose
OR
iron dextran: consult specialist for guidance on dose
OR
iron sucrose: consult specialist for guidance on dose
OR
ferumoxytol: consult specialist for guidance on dose
OR
ferric carboxymaltose: consult specialist for guidance on dose
calcium + vitamin D
Treatment recommended for ALL patients in selected patient group
There are no specific recommendations regarding prevention or treatment of calcium deficiency in patients with achlorhydria. Based upon recommendations for reducing fracture risk in older people, it would seem reasonable to give the dose used for this indication with a target serum 25-hydroxyvitamin D concentration of >20 nanograms/mL (>50 nanomol/L).
Calcium and vitamin D deficiency may be monitored by periodic serum 25-hydroxyvitamin D as well as bone mineral density testing.[145]Cauley JA, Lacroix AZ, Wu L, et al. Serum 25-hydroxyvitamin D concentrations and risk for hip fractures. Ann Intern Med. 2008 Aug 19;149(4):242-50. http://www.ncbi.nlm.nih.gov/pubmed/18711154?tool=bestpractice.com [146]Dawson-Hughes B, Harris SS, Krall EA, et al. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med. 1997 Sep 4;337(10):670-6. http://www.ncbi.nlm.nih.gov/pubmed/9278463?tool=bestpractice.com [147]Tang BM, Eslick GD, Nowson C, et al. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet. 2007 Aug 25;370(9588):657-66. http://www.ncbi.nlm.nih.gov/pubmed/17720017?tool=bestpractice.com
Primary options
calcium carbonate: 1000-1500 mg orally once daily
More calcium carbonateDose expressed as elemental calcium.
and
ergocalciferol (vitamin D2): 800 units orally once daily
Choose a patient group to see our recommendations
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer
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