The Clinical Benefits, Limitations, and Perspectives of the ABC Method

In Japan, over 99% of gastric cancer cases are associated with Helicobacter pylori infection (1). Because the grade of H. pylori-induced gastric atrophy correlates with gastric cancer development (2) and the serum pepsinogen (PG) levels reflect gastric mucosal atrophy, the combination of the PG test and the evaluation of the H. pylori antibody titer, a serological screening approach called the “ABC method” or “ABC classification,” efficiently and inexpensively stratifies the risk of gastric cancer in patients without a history of eradication (3).

The ABC method classifies patients into group A [H. pylori(-), PG(-)], H. pylori-negative; group B [H. pylori(+), PG(-)], H. pylori infection without extensive chronic atrophic gastritis (CAG); group C [H. pylori(+), PG(+)], H. pylori-induced extensive CAG; and group D [H. pylori(-), PG(+)], spontaneous disappearance of H. pylori due to severe CAG. This method can detect serologically negative but H. pylori-infected patients (group D) and thus is more accurate than H. pylori serology alone. Group B, C and D include candidates for endoscopy (3), and the cancer detection rate of the ABC method is 0.22%-0.42%, which is higher than historical data obtained by conventional X-ray mass screening (0.15%) (4). In the present report, the clinical benefits, limitations, and perspectives of the ABC method are discussed.

Few high-risk cases with gastric atrophy and gastric cancer are misclassified into group A, which is the “false group A problem” and regarded as the greatest weakness of the ABC method (5). Most of these patients have “past infection-induced atrophic gastritis” after normalization of PG and H. pylori serology caused by unintentional eradication through the incidental use of antibiotics (6). To avoid this misclassification, the cut-off value of the H. pylori antibody titer is set at a low value. In 2015, the Ministry of Health, Labor, and Welfare recommended population-based radiographic and endoscopic screenings for gastric cancer; however, the ABC method was not recommended because of the lack of direct evidence of mortality reduction. The high rate of patients for whom endoscopy is indicated (more than that in group B) is the other weakness of the ABC method, which requires improvement in the future.

In this issue of Internal Medicine, Kishino et al. reported that about 6.0% (364/6,105) of group A patients showed open-type gastric atrophy. The detection rates of gastric cancer in groups A, B, C, and D were 0.07% (4/6,105), 0.5% (8/1,739), 0.8% (16/2,010), and 1.1% (3/281), respectively. No gastric cancer was recognized among endoscopically normal cases (0/4,567); they therefore suggested that an evaluation by endoscopy is superior to the serological screening method (7).

Is the ABC method a relic of gastric cancer screening? No, it has clinical significance, and whether or not the mortality rate decreases when using this screening method should be determined. The benefits of the ABC method are its cost effectiveness and high sensitivity rate. As Kishino et al. reported, its sensitivity for detecting gastric cancer was 87% (27/31) (7), which is better than the rate of the immunological fecal occult blood test (65.8%) (8). Henceforth, the rate of gastric cancer is expected to significantly decrease because the infection rate of H. pylori has decreased (9). Intensive detection and monitoring of H. pylori-positive cases is effective, and the ABC method will become more useful, especially in populations with low H. pylori infection rates.

In addition, the ABC method can be used in various clinical settings, especially in east Asian countries in the following instances: 1) to detect high-risk cases if its limitations are recognized, and 2) to determine the H. pylori infection status and risk of future gastric cancer development for patients who refuse endoscopy or have undergone endoscopy. Furthermore, it motivates patients to undergo endoscopy, enables the potential eradication of H. pylori in positive cases, and provides information on the appropriate frequency of endoscopy in each case. Considering the decreasing infection rate of H. pylori and consequent decreasing incidence of gastric cancer in Japan, the clinical significance of the ABC method may become more important in the future.

The author states that he has no Conflict of Interest (COI).