The importance of transferrin in rapid Helicobacter pylori testing

Helicobacter pylori (H.pylori) infection remains one of the most prevalent digestive diseases worldwide and a significant clinical challenge due to its association with chronic gastritis, peptic ulcer disease, and gastric neoplasia¹. As discussed in the article ‘All about H.pylori: from infection to treatment. What you need to know’, early diagnosis and correct stratification are key to optimising patient management and healthcare resources.

In this context, the simultaneous detection of H.pylori antigen and transferrin in stool samples using a rapid test represents a significant advance in non-invasive diagnosis, as it allows both the infection caused by the pathogen and the possible existence of mucosal damage with gastrointestinal bleeding to be identified in a single step. Several clinical studies support this combined approach, highlighting its usefulness in the initial evaluation of patients with digestive symptoms^{2, 3}.

From mucosal damage to bleeding: why does transferrin appear in the stool?

Under physiological conditions, transferrin is a plasma protein present in blood serum, responsible for transporting iron, and is not detected in the gastrointestinal tract or faeces. However, chronic H.pylori infection causes persistent inflammation of the gastric mucosa, alteration of local defences and, in more advanced cases, the development of erosions or ulcers.

When the integrity of the mucosa is compromised, blood extravasates into the lumen of the digestive tract. The presence of transferrin in faeces is therefore considered an indirect marker of gastrointestinal bleeding, even when it is occult or not clinically evident.

Unlike haemoglobin, which is easily degraded in acidic environments and by the action of digestive enzymes, transferrin has greater molecular stability in the upper gastrointestinal tract. This characteristic makes it a particularly useful biomarker for detecting bleeding of gastric or duodenal origin^{2, 3, 4}.

Combined rapid stool tests: H.pylori + transferrin

Combined rapid tests on stool samples can simultaneously detect:

H. pylori antigen → indicator of infection.
Human transferrin → indicator of gastrointestinal bleeding.

Both qualitative results are obtained through a single, rapid, non-invasive procedure, providing relevant clinical information from the first contact with the patient.

Clinical interpretation of combined results

Scenario 1: H.pylori positive / transferrin negative

Suggests H.pylori infection without evidence of detectable gastrointestinal bleeding. May correspond to gastritis or mild lesions without significant vascular involvement. In this context, eradication treatment is usually a priority, reserving invasive techniques (such as endoscopy) for patients with warning signs or other risk factors.

Scenario 2: H.pylori positive / transferrin positive

Indicates infection associated with mucosal damage with bleeding. This pattern is consistent with bleeding peptic ulcer, extensive erosions, or other relevant lesions. From a clinical standpoint, it warrants preferential referral for endoscopy, monitoring for anaemia, and a more intensive therapeutic approach.

Scenario 3: H.pylori negative / transferrin positive

Rules out H.pylori infection but indicates gastrointestinal bleeding. In these cases, the test acts as a screening tool, guiding the investigation of other causes such as neoplasms, inflammatory bowel disease, or angiodysplasia.

Scenario 4: H.pylori negative / transferrin negative

A double negative result suggests the absence of infection and detectable bleeding. The clinician can assess other functional or organic non-bleeding aetiologies and decide on the need for additional tests according to the clinical context.

Advantages of the combined rapid test in clinical practice

Simultaneous response to two key questions: H. pylori infection and the presence of gastrointestinal bleeding.
Non-invasive method, particularly suitable for primary care, paediatrics and patients with comorbidities.
Better risk stratification, facilitating the prioritisation of endoscopies and other invasive tests.
Optimisation of healthcare resources, reducing unnecessary costs.
Post-eradication follow-up, allowing evaluation of antigen negativity and resolution of bleeding as a functional approximation to mucosal healing.

An efficient diagnostic approach aligned with current clinical practice

The simultaneous detection of H.pylori antigen and transferrin in stool using a rapid test integrates, in a single test, aetiological diagnosis and assessment of mucosal damage, providing a more complete picture of the patient’s condition from the early stages.

In a scenario of high H.pylori prevalence and a growing need to optimise diagnostic circuits, this type of combined test is establishing itself as a highly valuable tool for both primary care and specialised digestive tract units, laboratories and hospitals.

You can find more information about their rapid combined test for the detection of H.pylori and transferrin here.

1 – Olivares, D., & Gisbert, J. P. (2006). Factors involved in the pathogenesis of Helicobacter pylori infection. Revista Española de Enfermedades Digestivas, 98(5), 374–386. https://doi.org/10.4321/s1130-01082006000500008

2 – Lee, J.-M., Park, M. J., Heo, W., Park, K. G., Park, Y. G., Han, S. B., Cho, Y.-S., & Park, Y.-J. (2018). Clinical utility of fecal immunochemical transferrin test in gastrointestinal bleeding detection. Annals of Clinical Microbiology, 21(3), 51–57. https://doi.org/10.5145/ACM.2018.21.3.51

3 – Zhang, L., Yang, F., & Zhu, J. (2025). Distinctive Integrated Design and Clinical Utility of the Transferrin/FOB and Hb‑Hp Combo Rapid Test in Gastrointestinal Bleeding Diagnosis. MEDS Clinical Medicine, 6(5), 1–6. https://doi.org/10.23977/medsc.2025.060501

4 – Chen JG, Cai J, Wu HL, Xu H, Zhang YX, Chen C, Wang Q, Xu J, Yuan XL. Colorectal cancer screening: comparison of transferrin and immuno fecal occult blood test. World J Gastroenterol. 2012;18(21):2682-2688. doi:10.3748/wjg.v18.i21.2682.