Autoimmune gastritis (AIG) is a chronic progressive autoimmune disorder characterized by
the destruction of gastric parietal cells, leading to atrophy of the acid-secreting
gastric mucosa. The loss of parietal cells results in gastric acid deficiency and
intrinsic factor deficiency, which in turn impairs the absorption of iron and vitamin
B12, leading to clinical manifestations such as iron deficiency anemia, pernicious
anemia, and neuropsychiatric symptoms. Studies indicate that 4-12% of AIG patients
develop type 1 gastric neuroendocrine tumors (NETs), and these patients also face a 3-7
times higher risk of gastric adenocarcinoma, with an incidence rate ranging from 0.9% to
9%.
Currently, there are no anti-inflammatory, immunosuppressive, or biologic therapies
available for AIG. Standard treatment involves iron and vitamin B12 supplementation. Due
to progressive parietal cell destruction, AIG patients exhibit a hypochlorhydric state,
which reduces pepsin activity, impairs gastric motility, and may lead to small intestinal
bacterial overgrowth (SIBO), often causing symptoms such as dyspepsia. Additionally, low
gastric acid levels can interfere with the absorption of trace elements like iron and
calcium. Insufficient gastric acid also promotes bacterial overgrowth in the stomach and
increases N-nitroso compounds, elevating the risk of gastric cancer. Furthermore, gastric
hypochlorhydria triggers a feedback mechanism that stimulates gastrin secretion from
antral G cells, resulting in hypergastrinemia, which increases the risk of neuroendocrine
tumors. Supplementation with betaine hydrochloride (with pepsin) can lower gastric pH in
AIG patients, restore gastric acidity, improve protein digestion, alleviate dyspeptic
symptoms, enhance the absorption of vitamins and minerals, correct gastric dysbiosis and
SIBO, and reduce the risk of gastric cancer and neuroendocrine tumors.
This study aims to evaluate the effects of betaine hydrochloride (with pepsin) on gastrin
levels, gastrointestinal symptoms, exhaled gas markers (NO, H2S, H2, and CH4), iron
deficiency anemia parameters, AIG atrophy scores, and the incidence of gastric
complications (hyperplastic polyps, neuroendocrine tumors, and gastric cancer). The study
is divided into two groups: Group A (follow-up only, serving as the control group) and
Group B (oral betaine hydrochloride). The study adopts a non-randomized, open-label,
parallel-controlled design, where participants choose either the experimental group (oral
betaine) or the control group (follow-up only) based on their preference. Both groups
will be followed in parallel, and outcome differences will be compared, supplemented by
within-group pre- and post-intervention analyses.
The study population consists of AIG patients diagnosed at the Second Affiliated Hospital
of Zhejiang University School of Medicine. The diagnostic criteria for AIG are based on
our team's published article in Clinics and Research in Hepatology and Gastroenterology:
"A real-world study on the characteristics of autoimmune gastritis: A single-center
retrospective cohort in China." Inclusion criteria include: serum gastrin levels >300
pmol/L or a history of type 1 gastric NETs or early gastric cancer treated with
endoscopic submucosal dissection (ESD), age between 18 and 80 years, and signed informed
consent. Exclusion criteria include: allergy to betaine hydrochloride, presence of peptic
ulcers, other conditions causing elevated gastrin levels, and refusal to sign informed
consent.
Group A (control group) will undergo follow-up only without intervention, while Group B
will receive oral betaine hydrochloride (2 capsules three times daily with meals). The
primary outcomes include changes in serum gastrin levels and improvements in the
Gastrointestinal Symptom Rating Scale (GSRS). Secondary outcomes include changes in iron
deficiency anemia markers (serum iron, ferritin, hemoglobin), exhaled gas markers (NO,
H2S, H2, CH4), AIG atrophy scores, and the incidence of gastric complications
(hyperplastic polyps, NETs, and gastric cancer).
Data will be collected through questionnaires, laboratory tests, endoscopy, and
pathological records, with propensity score matching (PSM) used to adjust for baseline
differences. The study has been approved by the Ethics Committee of the Second Affiliated
Hospital of Zhejiang University School of Medicine. Adverse events will be monitored
regularly, and serious adverse events will be reported promptly to the ethics committee
and regulatory authorities.
This study will provide critical evidence on the efficacy and safety of betaine
hydrochloride in treating AIG, exploring a simple, cost-effective therapeutic approach to
alleviate symptoms and reduce the risk of severe complications.