HIV related hypochlorhydria does not appear to respond to anti-retroviral therapy in Zambian adults: a case control study.

INTRODUCTION: Human Immunodeficiency Virus (HIV) infection is associated with hypochlorhydria but the mechanism is unknown. The objective of this study was to determine effects of anti-retroviral therapy (ART) on gastric physiology as measured by validated markers. METHODS: We studied HIV infected individuals who were either ART-naïve or on treatment with undetectable viral loads. We measured H.pylori IgG antibodies, pepsinogen (PG) 1 and 2 levels and fasting gastrin-17 using Biohit GastroPanel®. Gastric antral biopsies and juice were obtained for histology and pH respectively. Also included were historical data from HIV negative participants (n = 72) in a previous study, for reference. RESULTS: We enrolled 84 HIV positive individuals with a median age 42 years (IQR 37-40 years). 55(66%) were female, 32(38%) were ART naïve, and 52(62%) were on ART. Hypochlorhydria (pH>4) was present in 48(57%) of the HIV positive and 18(25%) of the HIV negative individuals (OR 4: 95% CI 1.9-8.5, P<0.001) with no significant effect of ART (OR 0.9: 95% CI 0.3-2.3, P = 0.82). Hypochlorhydria was not associated with the serological detection of corpus atrophy using low PG 1:2 ratio (OR 2.1: 95% CI 0.5-10.2, P = 0.37) or GastroPanel® algorithm, (OR 0.7: 95% CI 0.01-60.1, P = 1.0). ART reduced the frequency of low PG 1:2 ratio (P = 0.001), but not the histological detection in the antrum of atrophy or non-atrophic gastritis. CONCLUSION: ART use is associated with reduced serological evidence of corpus atrophy but has no effect on fasting pH, supporting earlier data that suggest that the mechanism of HIV-associated hypochlorhydria is multifactorial.

Netazepide, a gastrin/cholecystokinin-2 receptor antagonist, can eradicate gastric neuroendocrine tumours in patients with autoimmune chronic atrophic gastritis.

AIMS: Netazepide, a gastrin/cholecystokinin 2 receptor antagonist, once daily for 12 weeks reduced the number of tumours and size of the largest one in 16 patients with autoimmune chronic atrophic gastritis (CAG), achlorhydria, hypergastrinaemia and multiple gastric neuroendocrine tumours (type 1 gastric NETs), and normalized circulating chromogranin A (CgA) produced by enterochromaffin-like cells, the source of the tumours. The aim was to assess whether longer-term netazepide treatment can eradicate type 1 gastric NETs. METHODS: After a mean 14 months off netazepide, 13 of the 16 patients took it for another 52 weeks. Assessments were: gastroscopy; gene-transcript expression in corpus biopsies using quantitative polymerase chain reaction; blood CgA and gastrin concentrations; and safety assessments. RESULTS: While off-treatment, the number of tumours, the size of the largest one, and CgA all increased again. Netazepide for 52 weeks: cleared all tumours in 5 patients; cleared all but one tumour in one patient; reduced the number of tumours and size of the largest one in the other patients; normalized CgA in all patients; and reduced mRNA abundances of CgA and histidine decarboxylase in biopsies. Gastrin did not increase further, confirming that the patients had achlorhydria. Netazepide was safe and well tolerated. CONCLUSIONS: A gastrin/cholecystokinin 2 receptor antagonist is a potential medical and targeted treatment for type 1 gastric NETs, and an alternative to regular gastroscopy or surgery. Treatment should be continuous because the tumours will regrow if it is stopped. Progress can be monitored by CgA in blood or biomarkers in mucosal biopsies.

Calcium gluconate supplementation is effective to balance calcium homeostasis in patients with gastrectomy.

UNLABELLED: We demonstrate histological evidence for hyperparathyroidism in patients with gastrectomy. This is, at least in part, explained by impaired calcium absorption, resulting in mineralization defects and secondary hyperparathyroidism. Additionally, we demonstrate improved bone mineralization in patients with gastrectomy after gluconate therapy and showed the effectiveness of calcium gluconate over carbonate to balance impaired calcium hemostasis in mice. INTRODUCTION: Gastrectomy and hypochlorhydria due to long-term proton pump inhibitor therapy are associated with increased fracture risk because of intestinal calcium malabsorption. Hence, our objectives were to histologically investigate bone metabolism in patients with gastrectomy and to analyze the impact of calcium gluconate supplementation on skeletal integrity in the setting of impaired gastric acidification. METHODS: Undecalcified bone biopsies of 26 gastrectomized individuals were histologically analyzed. In the clinical setting, we retrospectively identified 5 gastrectomized patients with sufficient vitamin D level, who were additionally supplemented with calcium gluconate and had a real bone mineral density (aBMD) follow-up assessments. A mouse model of achlorhydria (ATP4b-/-) was used to compare the effect of calcium gluconate and calcium carbonate supplementation on bone metabolism. RESULTS: Biopsies from gastrectomized individuals showed significantly increased osteoid, osteoclast, and osteoblast indices and fibroosteoclasia (p < 0.05) as well as impaired calcium distribution in mineralized bone matrix compared to healthy controls. Five gastrectomized patients with sufficient vitamin D level demonstrated a significant increase in aBMD after a treatment with calcium gluconate alone for at least 6 months (p < 0.05). Calcium gluconate was superior to calcium carbonate in maintaining calcium metabolism in a mouse model of achlorhydria. CONCLUSION: Gastrectomy is associated with severe osteomalacia, marrow fibrosis, and impaired calcium distribution within the mineralized matrix. We show that calcium gluconate supplementation can increase bone mineral density in gastrectomized individuals and performs superior to calcium carbonate in restoring calcium/skeletal homoeostasis in a mouse model of achlorhydria.

Gastric reacidification with betaine HCl in healthy volunteers with rabeprazole-induced hypochlorhydria.

Previous studies have demonstrated that increased gastric pH from the use of acid-reducing agents, such as proton-pump inhibitors or H2-receptor antagonists, can significantly impact the absorption of weakly basic drugs that exhibit pH-dependent solubility. Clinically practical strategies to mitigate this interaction have not been developed. This pilot study evaluated the extent and time course of gastric reacidification after a solid oral dosage form of anhydrous betaine HCl in healthy volunteers with pharmacologically induced hypochlorhydria. Six healthy volunteers with baseline normochlorhydria (fasting gastric pH < 4) were enrolled in this single period study. Hypochlorhydria was induced via 20 mg oral rabeprazole twice daily for four days. On the fifth day, an additional 20 mg dose of oral rabeprazole was given and gastric pH was monitored continuously using the Heidelberg pH capsule. After gastric pH > 4 was confirmed for 15 min, 1500 mg of betaine HCl was given orally with 90 mL of water and gastric pH was continuously monitored for 2 h. Betaine HCl significantly lowered gastric pH by 4.5 (± 0.5) units from 5.2 (± 0.5) to 0.6 (± 0.2) (P < 0.001) during the 30 min interval after administration. The onset of effect of betaine HCl was rapid, with a mean time to pH < 3 of 6.3 (± 4.3) min. The reacidification period was temporary with a gastric pH < 3 and < 4 lasting 73 (± 33) and 77 (± 30) min, respectively. Betaine HCl was well tolerated by all subjects. In healthy volunteers with pharmacologically induced hypochlorhydria, betaine HCl was effective at temporarily lowering gastric pH. The rapid onset and relatively short duration of gastric pH reduction gives betaine HCl the potential to aid the absorption of orally administered weakly basic drugs that exhibit pH-dependent solubility when administered under hypochlorhydric conditions.

Reducing carcinogenic acetaldehyde exposure in the achlorhydric stomach with cysteine.

BACKGROUND: Acetaldehyde, associated with alcohol consumption, has recently been classified as a group 1 carcinogen in humans. Achlorhydric atrophic gastritis is a well-known risk factor for gastric cancer. Achlorhydria leads to microbial colonization of the stomach. Several of these microbes are able to produce significant amounts of acetaldehyde by oxidation from alcohol. Acetaldehyde can be eliminated from saliva after alcohol intake and during smoking with a semi-essential amino acid, L-cysteine. The aim of this study was to determine whether cysteine can be used to bind acetaldehyde in the achlorhydric stomach after ethanol ingestion. METHODS: Seven volunteers with achlorhydric atrophic gastritis were given either slow-release L-cysteine or placebo capsules in a double-blinded randomized trial. Volunteers served as their own controls. A naso-gastric tube was inserted to each volunteer. The volunteers ingested placebo or 200 mg of L-cysteine capsules, and ethanol 0.3 g/kg body weight (15 vol%) was infused intragastrically through a naso-gastric tube. Five-milliliter samples of gastric contents were aspirated at 5-minute intervals. RESULTS: During the follow-up period, the mean acetaldehyde level of gastric juice was 2.6 times higher with placebo than with L-cysteine (13 vs. 4.7 µM, p < 0.05, n = 7). CONCLUSIONS: L-cysteine can be used to decrease acetaldehyde concentration in the achlorhydric stomach during alcohol exposure. Intervention studies with L-cysteine are needed on reducing acetaldehyde exposure in this important risk group for gastric cancer.

Watery diarrhea, hypokalemia, achlorhydria syndrome in an infant: effect of the long-acting somatostatin analogue SMS 201-995 on the disease and linear growth.

An 8-week-old infant presented with vomiting and failure to thrive due to small bowel obstruction caused by a diffusely enlarged pancreas. Surgical bypass of the obstruction was followed by secretory diarrhea, hypokalemia, and dehydration. Plasma vasoactive intestinal peptide (VIP) (823pg/ml), pancreatic polypeptide (4,500 pg/ml), and neurotensin (680 pg/ml) concentrations were markedly elevated. No neoplastic process was identified. Therapy with the long-acting somatostatin analogue SMS 201-995 was followed by decline in VIP concentrations (900 to 200-300 pg/ml), decrease in stool frequency, and normalization of serum electrolytes. During 12 months of somatostatin analogue therapy, length and weight progressed along the 3rd percentile on the Tanner growth chart.

Antral vascular lesion, achlorhydria, and chronic gastrointestinal blood loss: response to steroids.

A 72-year-old female gave a history of chronic gastrointestinal blood loss necessitating transfusion with over 90 units of blood despite continuous oral iron therapy over a period of 24 years. Gastroscopic appearances were very similar to those recently described by Lewis and by Wheeler in patients with submucosal angiomatous lesions and chronic gastrointestinal blood loss. Striking erythematous streaks radiated from the pylorus and were confined to the antrum. In our case complete achlorhydria to pentagastrin was associated with low serum and antral gastrin concentrations. The introduction of oral prednisolone was followed by a marked fall in the rate of gastrointestinal blood loss, removing the need for transfusion during the following year. Complete achlorhydria persisted and endoscopic appearances remained unchanged, but there was a marked rise in antral and serum gastrin concentrations. The possible modes of action of prednisolone in this case are discussed. The patient remains well in November 1979. The dose of prednisolone was reduced to 10 mg on alternate days in May 1979. Iron supplements have been continued but no transfusion has been required since the start of steroid therapy. The hemoglobin has gradually risen to 14.9 g/dl.