4 | DISCUSSION
Several endoscopic features of the gastric mucosa have been proposed for
the diagnosis of H. pylori infection, such as RAC, diffuse or spotty
redness, mucosal swelling, and nodular changes(1). Our study included 15
relevant studies(17-31) assessing the diagnostic accuracy of RAC for H.
pylori, and the results suggest that RAC has a high diagnostic accuracy
for H. pylori infection, with a pooled estimate of 0.98 (95% CI 0.95 to
0.99) for sensitivity and 0.75 (95% CI 0.54 to 0.88) for specificity.
Many studies have evaluated the diagnostic accuracy of RAC as a single
endoscopic feature for H. pylori, with inconclusive results. A
prospective study in a European population enrolling 140 adults found
that the presence of RAC in the lesser curvature evaluated with
high-definition endoscopy can help identify patients without H. pylori,
with a sensitivity of 100% and a specificity of 48.96%(20). A
prospective study in Korea involving 617 individuals concluded that the
RAC pattern observed using standard endoscopy could predict H. pylori
infection status, with a sensitivity of 93.3% and a specificity of
89.1%(19). Again, in a Brazilian cohort of 99 individuals, Machado et
al. investigated the diagnostic accuracy of RAC for H. pylori,
suggesting that RAC can provide a sensitivity of 96.9% and a
specificity of 88.1% for diagnosing H. pylori infection(26).
In a meta-analysis from 2020 including studies published between 2002
and 2019, Li and colleagues concluded that RAC is a valuable endoscopic
finding for predicting patients without H. pylori infection(37).
However, this meta-analysis has substantial shortcomings in its
quantitative data analysis for heterogeneity, with a reported
I2 of 0 (95% CI: 0-100%). In contrast, our study
found significant heterogeneity between studies, with an
I2 of 99.95% (95% CI: 99-100%). Furthermore, we
performed a univariable meta-regression and subgroup analysis to
identify the potential source of heterogeneity between the studies. The
results showed that whether patients with a history of H. pylori
infection were excluded and whether consecutive enrollment was used in
each study significantly affected the sensitivity of RAC, indicating
that these two factors might partly contribute to the heterogeneity
between studies.
Likelihood ratios and posttest probabilities are also of importance
because they provide information regarding the likelihood that a patient
with a positive or negative test has H. pylori infection or not. In our
study, a positive likelihood ratio of 3.8 implies that a person with H.
pylori infection is 3.8 times more likely to have a positive test result
than is a healthy person. Likewise, a negative likelihood ratio of 0.03
indicates that a person without H. pylori infection is 33 times more
likely to have a negative test result than is a person with H. pylori
infection. Therefore, RAC can serve as a reliable marker for exclusion
rather than confirmation of H. pylori infection.
As our results show, RAC is not a perfect endoscopic marker for the
diagnosis of H. pylori. Although RAC has a high overall diagnostic
accuracy for H. pylori infection, it is not a good predictor for
confirming H. pylori infection because of its low positive likelihood
ratio. The pathophysiological process of H. pylori infection is complex
and can be affected by many factors, which probably contributes to the
variations in endoscopic findings(38-41). Therefore, a single endoscopic
feature of RAC might be insufficient for confirmation of H. pylori
infection because of the relatively low positive likelihood ratio, thus
highlighting the need for a combination of multiple endoscopic features
to confirm H. pylori infection.
This study has limitations. First, we detected substantial heterogeneity
between the studies and found that two of the study characteristics
contributed to the observed heterogeneity. However, there are probably
additional study characteristics that have impacted study heterogeneity
but have not been addressed, such as sample size, geographic area,
variation in the methods used for the diagnosis of H. pylori between
studies, and variation in the anatomic location where endoscopic
physicians observed the RAC, because these factors were challenging to
quantitatively analyze. Second, we only included studies written in
English, which might have led to selection bias, although the funnel
plot did not reveal significant publication bias (p=0.37). Third, this
systematic review did not include studies that assessed endoscopic
features other than RAC that are possibly associated with H. pylori
infection. Despite these limitations, this meta-analysis investigating
the diagnostic accuracy of RAC for H. pylori infection is the largest
and most comprehensive assessment to date.