Treatments for achlorhydria and the physiologic consequences of this condition are discussed in this section.
H pylori–associated achlorhydria
Achlorhydria associated with H pylori infection may respond to H pylori eradication therapy, although resumption of gastric acid secretion may only be partial.
The standard, first-line therapy for gastric H pylori is as follows: PPI (20 mg bid) plus clarithromycin (500 mg bid) plus amoxicillin (1 g bid). For patients who are allergic to penicillin, amoxicillin can be replaced by levofloxacin (250 mg bid).
There is some minor disagreement on the duration of treatment. US guidelines recommend a 14-day course, while in Europe, a 7-day course is considered to be sufficient. A meta-analysis reveals a 12% advantage for a longer course of treatment, but this is at an added expense and a greater risk of adverse effects. Patient compliance is also more difficult with a longer course of treatment (ie, 14 d vs 7 d).
In immune-mediated diseases (eg, pernicious anemia), acid secretion cannot be restored after destruction of the gastric secretory mucosa.
Treatment of gastritis that leads to pernicious anemia consists of parenteral vitamin B-12 injection. It is not clear whether intranasal vitamin B-12 therapy is adequate in individuals who have been diagnosed with pernicious anemia. Parenteral vitamin B-12 treatment may reverse hematologic abnormalities. However, it may have little effect on preexisting neurologic abnormalities. This treatment does not affect the underlying gastric atrophy, inflammation, or the possible development of gastric carcinoma and should be followed with these risks in mind.
Associated immune-mediated conditions (eg, insulin dependent diabetes mellitus, autoimmune thyroiditis) should also be treated. However, treatment of these disorders has no known beneficial effect on achlorhydria.
The normal indigenous intestinal microflora consists of about 1015 bacteria that mainly reside in the lower gut. Bacterial overgrowth implies abnormal bacterial colonization of greater than 100,000/mL in the upper gut.
Small intestinal bacterial overgrowth can result in recurrent diarrhea with malabsorption, D-lactic acidosis, and an increased risk of endogenous infection. Other conditions associated with small bowel bacterial overgrowth include steatorrhea, macrocytic anemia, and, less commonly, protein-losing enteropathy.
Microecologic changes are accompanied by vitamin B-12 deficiency anemia, hypovitaminosis, protein deficiency, translocation of bacteria and their toxins from the intestine into the bloodstream, emergence of endotoxinemia, and possible generalization of infection. Bacterial overgrowth is diagnosed by concentration of hydrogen in expiratory flow (glucose-hydrogen breath test) or by bacteriological study of aspirate from the proximal part of the small intestine.
Antimicrobial agents, including metronidazole, amoxicillin/clavulanate potassium, ciprofloxacin, and rifaximin, can be used to treat bacterial overgrowth.
Long-term PPI use
Achlorhydria resulting from long-term proton pump inhibitor (PPI) use may be treated by dose reduction or withdrawal of the PPI.
Achlorhydria from PPI use may also be corrected by administration of hydrochloric acid supplements. More recently, betaine hydrochloride (BHCl) has been used as a gastric acid supplement and is available over the counter as a nutraceutical. In healthy volunteers with pharmacologically induced hypochlorhydria, BHCl has been shown to temporarily reduce the gastric pH, but cessation of PPI therapy is often enough to correct medication-induced achlorhydria. 
Hypergastrinemia due to achlorhydria secondary to PPI therapy or resection of the gastric fundus is known to cause ECL cell hyperplasia and gastric carcinoids. Surgery is the only potentially curative therapy for carcinoid tumors. 
Surgical antrectomy results in normalization of serum gastrin levels and disappearance of multicentric gastric carcinoids. In a study by Hirschowitz et al, antrectomy resulted in normalization of serum gastrin levels within 8 hours and disappearance of carcinoids in 6-16 weeks. 
Gladdy et al examined the efficacy of endoscopic surveillance versus surgical resection in the treatment of patients with type I GI carcinoid tumors.  In the study, 46 patients underwent endoscopic surveillance with polypectomy, while 19 patients were treated with gastric resection. (The latter treatment was used in patients with larger-sized tumors, increased depth of invasion, and solitary tumors.) The 5-year recurrence-free survival rate was 75% in the surgical resection patients, but the disease-specific survival rate was 100% in both patient groups. Concomitant adenocarcinoma was found in 4 of the patients who underwent resection, with the detection made through preoperative biopsy in 2 of these individuals. (The carcinoid tumors were bigger and the carcinoid disease was more advanced in all patients with coexisting gastric adenocarcinoma.)
The authors recommended that resection be considered for patients with more advanced carcinoid disease, owing to the increased adenocarcinoma risk associated with the advanced disorder. They also concluded that endoscopic surveillance is appropriate for determining the status of carcinoid tumors and for the assessment of the dysplasia or adenocarcinoma that can arise in association with type I GI carcinoid tumors.
Patients with achlorhydria may develop ECL cell hyperplasia and gastric carcinoids. However, most experts believe that regular upper endoscopic surveillance is not justified.
Achlorhydria leads to hypergastrinemia. The trophic effect of gastrin leading to colorectal adenocarcinoma has been observed in knockout mouse models.
Patients on long-term PPI treatment may develop drug-induced achlorhydria. These patients have been observed to have reduced serum vitamin B-12 (cobalamin) levels. Vitamin B-12 injections may be indicated in this subgroup.
Bacterial overgrowth and subsequent micronutrient deficiencies can occur in patients with achlorhydria. Patients with a history of gastric bypass surgery or long-term PPI use are predisposed to bacterial overgrowth. These patients should be tested for various nutrient deficiencies, including thiamine levels and calcium levels. Patients should undergo hydrogen breath testing. If the test results are positive, these patients should be treated with antimicrobial therapy for bacterial overgrowth. The patients should receive appropriate supplements to correct deficient nutrients. However, this supplementation may not be sufficient to maintain adequate nutrient levels without the treatment of the bacterial overgrowth.
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