RAC presence has been well known as a characteristic endoscopic feature in H. pylori-negative normal stomach [6, 7]. In 2002, Yagi et al.  researchers have indicated that the presence of RAC for predicting H. pylori-negative normal stomach had 93.8% sensitivity and 96.2% specificity. In many subsequent studies [8–17], the RAC-positive pattern also demonstrated a high specificity between 85.7% and 100%, however, the sensitivity of RAC-positive pattern varied from 93.5–48.0%. In our study, RAC presence has only 51.4% sensitivity and 71.0% NPV for predicting H. pylori-negative status in routine clinical practice despite a good specificity (96.7%) and PPV (92.7%). These studies strongly supported the idea that the presence of RAC in the lesser corpus can accurately identify H. pylori-negative gastric body mucosa , but RAC absence did not always point out H. pylori-positive corpus mucosa.
In clinical practice, many H. pylori-related and -unrelated factors can cause the disappearance of RAC, such as chronic active gastritis caused by current H. pylori infection, chronic inactive gastritis after H. pylori eradication, H. pylori-negative gastritis, and gastropathy induced by liver cirrhosis, et al [6, 25–28]. In patients with chronic active gastritis, in addition to the disappearance of RAC, H. pylori status can be assessed by combination with other endoscopic manifestations, such as diffuse redness, spotty redness and swelling of areae gastricae . Shiota et al.  and Nordenstedt et al.  had found H. pylori-negative gastritis in 17.7% and 21% of patients with histologic gastritis. Although H. pylori-negative gastritis is a condition that cannot be ignored, the diagnosis process is complicated and difficult to apply in daily work [29, 30]. Thus, we have not further evaluated such patients with H. pylori-negative gastritis in the present study. In inclusion criteria, the patients with liver cirrhosis have been excluded. NSAIDs were also one of the common causes of gastropathy. Our results revealed that no significant differences in RAC pattern were found in a small group of patients treated with NSAIDs, which was consistent with previous studies .
H. pylori-eradicated cases have been arising considering the preventive effect of H. pylori eradication therapy for gastric cancer . However, RAC will not reappear immediately after H. pylori eradication. Yagi et al.  have revealed that RAC did not recover for over one year in 68% subjects after successful H. pylori eradication. Garces-Duran et al.  also found that about half of past H. pylori-eradicated patients were RAC-negative. Thus, RAC would be invisible in a considerable proportion of H. pylori-eradicated patients. We found that RAC was still absent in about two-thirds of patients (67.7%, 21/31) with H. pylori eradication history. These results revealed that RAC absence did not always indicate H. pylori-positive status in patients with H. pylori eradication history. Although detailed medical records were very vital for identifying the eradicated cases, some patients still failed to provide past H. pylori eradication clearly. In addition, partially eradicated patients may come from unintended H. pylori sterilization because of the infectious diseases in other organs. Besides, H. pylori may be also naturally eradicated without bactericidal therapy. These conditions made it difficult for us to accurately judge the past infection of H. pylori in clinical practice. Therefore, we investigated the total H. pylori prevalence in RAC-negative patients, and found that only 71.0% (88/124) subjects were H. pylori positive. 29.0% (36/124) of patients were H. pylori-negative status although RAC disappeared, which resulting in the low sensitivity (51.4%) and NPV (71.0%).
In these reports [6, 8–17] on the relationship between RAC pattern and H. pylori status, the sensitivity of RAC varied greatly from 93.8–48.0%, which may be related to different baseline characteristics of the patients and multiple methods of H. pylori status judgment. Among the 11 studies, four studies [9, 11, 13, 17] simultaneously detected H. Pylori in gastric body and antrum by histological examination and rapid urease test (RUT), and showed that the sensitivity of RAC decreased from 92.8–49.0% due to the difference in baseline characteristics. For example, in Garces-Duran et al.  study the patients with NSAIDs usage and past H. pylori eradication were enrolled, and the sensitivity was only 49.0%. In the present study, we did not also exclude analogous patients and the sensitivity was low (51.4%). Even if the patients with H. pylori eradication history were excluded in inclusion criteria, the sensitivity was only 66.7% in Yan et al.  study and 48.0% in Kato et al.  study. Indeed, in clinical work, it is very difficult for us to completely exclude insidious past H. pylori infection, especially unintended H. pylori sterilization and spontaneous eradicators mentioned above. Interestingly, the two studies [14, 15] only detected H. pylori in gastric body by histology and/or RUT. Therefore, the prevalence of H. pylori could only reflect the H. pylori status in the corpus, which was similar to our study. One studies  merely detected H. pylori in the antrum by histology and RUT, which can not reveal the infection of H. pylori in gastric body because in some patients the infection only affected gastric antrum . Indeed, it was not appropriate to use RAC in the body to predict H. pylori status in the antrum in this study.
RAC absence is one of the main manifestations of chronic active gastritis due to H. pylori current infection [6, 7, 12]. Gastric mucosal active inflammation should relieve shortly after eradication of H. pylori, however, RAC was still negative in some patients [17, 26]. Mild chronic inflammation in gastric mucosa can persist for more than 5 years after successful H. pylori eradication therapy in up to one-fifth of patients . The appearance of RAC was the endoscopic manifestation of normal gastric corpus mucosa without pathologic changes [33, 34]. Saghier et al.  study has showed that foveolar length of corpus mucosa in H. pylori gastritis patients was significantly increased than that of normal H. pylori-uninfected gastric corpus. In a recent study from our team , we found that the prolongation of gastric foveolae could result in the invisibility of RAC. We revealed that in addition to H. pylori current infection, chronic inactive gastritis in H. pylori-eradicated patients can also cause RAC disappearing through the prolongation of gastric foveolae. Therefore, along with the increase of H. pylori-eradicated patients, the subjects with RAC-negative and H. pylori-negative entity are further accumulating, which can lead to decreasing sensitivity. Hence, only RAC disappearance was not a reliable feature to judge H. pylori positive status in daily practice. In fact, in Yagi et al. study , the predicting corpus mucosa of RAC presence was not only H. pylori negative status but also normal pathological features. However, in many studies [8–17], only H. pylori status was evaluated, ignoring gastric mucosa pathological abnormality, in particular the changes of gastric foveolae length. In a word, RAC presence was the endoscopic manifestation of normal gastric corpus mucosa with normal histology [33, 34], which can not only exclude H. Pylori infection, but also eliminate the pathological abnormalities of corpus mucosa caused by other factors.
Our study had several limitations: Firstly, our study only explored the relationship between RAC and H. Pylori infection in gastric corpus mucosa, and H. pylori status of gastric antrum mucosa was not evaluated. Therefore, H. Pylori status of gastric corpus cannot be represented the entire stomach. Secondly, histological detection of H. pylori can reduce the accuracy because of patchy distribution of the bacteria. Combination of multiple methods was helpful to more accurate detection of H. Pylori such as urea breath test, serological examination, PCR and culturing. However, PCR and H. pylori culturing was not convenient in daily clinical practice. In addition, urea breath test and serological examination cannot distinguish the patients in which the gastric body was only affected, and not be performed in the present study. Thirdly, RAC accuracy may be influenced by patient age . We did not conduct age stratification analysis due to the limited sample size. Lastly, this was a single-center study, with a limited number of cases and a short time span. In future, more patients can be included to analyze different detective methods of H. pylori and different patient subgroups to strengthen our results.