Approach

There is no specific treatment for achlorhydria. Routine endoscopic surveillance is not recommended in the US.[72]

Because Helicobacter pylori, an infection considered carcinogenic by 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.[23][72][73] Atrophic gastritis in the oxyntic mucosa (fundus and corpus), but not necessarily intestinal metaplasia, may improve when re-examined 10 years after H pylori eradication.[126] However, these findings are controversial.[92][93][127]

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 medications.

Helicobacter pylori infection

An acceptable H pylorieradication regimen is generally defined as one that reliably offers cure rates of at least 90%.[128]

First-line treatment

Two first-line quadruple eradication regimens, recommended by guidance, have been shown to have cure rates of at least 90%:[91][129][130][131][132][133][134] 

  • Proton-pump inhibitor (PPI) (e.g., omeprazole - other PPIs are also suitable) plus amoxicillin plus clarithromycin plus metronidazole

  • PPI plus bismuth plus metronidazole plus tetracycline (or doxycycline if tetracycline is not available).

Although some guidelines recommend 10 to 14 days of therapy, 14 days of therapy is generally recommended as increasing the duration of treatment improves the eradication rate without significantly increasing adverse events.[91][129][131][135][136][137][138][139][140][141][142][143]

Second-line treatment

Patients who fail first-line therapy should be re-treated with regimens that do not include previously used antibiotics, except for amoxicillin and tetracycline as resistance to later antibiotics is rare.[21][91][129] Those with a penicillin allergy should be considered for allergy testing. 

Second-line regimens after first-line regimen failure include:[21][91][129]

  • PPI plus amoxicillin plus levofloxacin

  • High-dose PPI plus high-dose amoxicillin

  • PPI plus rifabutin plus amoxicillin.

Fourteen days of therapy is recommended for these regimens, although the rifabutin-based regimen may be given for 10 to 14 days.[129][144][145]

Due to complexity and poor adherence, sequential non-bismuth and hybrid non-bismuth quadruple therapy are no longer recommended.[129][146]

High-dose dual therapy, defined as the administration of a high dose of a PPI plus a high dose of amoxicillin, is effective following first-line therapy failure (70% to 89%), and circumvents the issue of clarithromycin, metronidazole, and levofloxacin resistance.[147][148]

Rifabutin-based regimens are effective rescue therapies as H pyloriresistance to this commonly used anti-tuberculosis drug is uncommon.[91][98][73][128][129][131][149][150][151][152][153][154] Although myelotoxicity was observed in 2% of treated patients, all of them recovered without increased susceptibility to infection.[155]

Antibiotic resistance

Standard first-line empirical initial treatment for H pylori infection is triple therapy consisting of a PPI, amoxicillin, and clarithromycin for 14 days.[91][129] However, treatment success with this regimen is presently <80%, in both the US and Europe, primarily related to an increase in the prevalence of clarithromycin resistance and poor treatment adherence; evidence suggests that this regimen should no longer be recommended.[130][156]

Resistance to other antibiotics, traditionally used in H pylorieradication regimens, has also increased. In the US, resistance to metronidazole is 20% and to levofloxacin 31%. Fortunately, antibiotic resistance to tetracycline and amoxicillin is low to rare.[156][157] Poor treatment adherence is related to complex treatment regimens and adverse effects to antibiotics. 

Confirmation of treatment efficacy

Treatment success (or failure) should be confirmed using urea breath test, stool antigen test, or biopsy with immunohistochemistry or rapid urease test.[128] The tests should be performed at least four weeks after completion of the eradication regimen. PPIs, which are bacteriostatic against H pylori, should be withheld for one to two weeks prior to testing.[129][158][159][160] There is some evidence that certain stool antigen tests that use monoclonal antibodies may be reliable even in the presence of PPIs.[161]

Individualised treatment

Patient management should be individualised and tailored. It is the view of the contributors that a one-size-fits-all approach to H pylori eradication is not necessarily in the best interest of patients. The decision whether or not to undertake H pylorieradication therapy should be based upon the clinical indication, age, family history, and underlying comorbidities of the patient, as well as potential benefits versus harms of first-line and second-line antibiotic regimens. Good antibiotic stewardship enhances patient health outcomes and reduces antibiotic resistance. 

Cobalamin deficiency

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

Iron deficiency

Oral iron, along with ascorbic acid (vitamin C), 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.[162]

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, delavirdine, atazanavir, ketoconazole, itraconazole, cefpodoxime, enoxacin, and dipyridamole).[163][164][165][166][167] An increased dose may be necessary to achieve efficacy.

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