Approach

There is no specific treatment for achlorhydria. Routine endoscopic surveillance is not recommended in the US.[67]

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][67]​​ 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] However, these findings are controversial.[88][89][125]

Other treatments are designed to prevent and/or treat complications arising from achlorhydria, such as cobalamin, iron, and calcium deficiency as well as impaired absorption of certain drugs.

Helicobacter pylori infection

An acceptable H pylorieradication regimen is generally defined as one that reliably offers cure rates of at least 90%.[126]​ Adherence to the complete treatment regimen is essential for successful eradication.

First-line treatment

The American College of Gastroenterology (ACG) recommends empirical first-line regimens for treatment-naive patients with H pylori infection. Optimised 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]

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

  • 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][127]

​Potassium-competitive acid blockers have been reported to have a more rapid onset of action and a longer duration of acid suppression than PPIs.[128]​ One randomised controlled trial found that potassium-competitive acid blocker dual and triple therapy were superior to PPI-based triple therapy in treatment-naive H pylori infection, including in clarithromycin-resistant strains.[129]​ Systematic reviews report greater H pylori eradication rates when vonoprazan is substituted for the PPI in clarithromycin-based triple therapies, and superior H pylori eradication rates (compared with PPI-containing regimens), for the treatment of clarithromycin-resistant H pylori strains.[130][131]

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]

All H pylori eradication regimens contain antibiotics and therefore may cause diarrhoea, promote opportunistic infections, and interfere with absorption of many other drugs, including oral contraceptives. There is insufficient evidence to suggest that the use of probiotic therapy improves the efficacy or tolerability of H pylori eradication therapy.[92]

Check for eradication of H pylori at least 1 month after the end of therapy with an appropriately conducted urea breath test, faecal antigen test, or biopsy-based test.​[91][92]​​ Continuation of acid suppressive therapy after treatment of infection is not necessary in most patients.

Subsequent treatment

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][132]

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]​ 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]

Antibiotic resistance

To optimise the management of H pylori infection, eradication therapy should be based on patterns of local and individual antimicrobial resistance.[133][134]​​ 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]​ However, H pylori culture and molecular testing is not widely available in all countries.[136]

​Individualised treatment

Patient management should be individualised and tailored. Good antibiotic stewardship enhances patient health outcomes and reduces antibiotic resistance.

Cobalamin deficiency

Cobalamin deficiency can be treated with parenteral (intramuscular) cyanocobalamin (vitamin B12).

Iron deficiency

Oral iron is used to treat iron deficiency. Parenteral iron can be given intramuscularly but preferentially intravenously. The iron deficit is calculated based on the premise that 1 g of haemoglobin contains 3.3 mg of elemental iron. Traditionally, oral ferrous sulfate is prescribed; there is evidence to suggest that once daily or alternate daily dosing regimens may optimise iron absorption and decrease adverse effects compared with standard regimens.[137] 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.

Calcium deficiency

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 similar doses with a target serum 25-hydroxyvitamin D concentration of >50 nanomol/L (>20 nanograms/mL).

Impaired drug absorption

Reduced acid secretion may impair the absorption of some drugs (e.g., levothyroxine, atazanavir, ketoconazole, itraconazole, cefpodoxime, dipyridamole).[138][139][140][141][142]​ An increased dose may be necessary to achieve efficacy.

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