Regression of Autoimmune Gastritis after Eradication of Helicobacter pylori

Autoimmune gastritis (AIG), a type of chronic atrophic gastritis, is characterized by immune-mediated inflammation that progressively destroys the parietal cells in fundic glands. Helicobacter pylori infection is one possible cause of AIG [1‒4]; indeed, gastric atrophy improves after bacteria eradication in patients with H. pylori-positive AIG [5‒7]. However, an experimental murine AIG model reported contrary findings, in which H. pylori infection suppressed development of AIG [8], and a recent case report suggested that AIG progressed after H. pylori eradication [9]. Here, we report a case of H. pylori-positive AIG in which regression of AIG after eradication therapy was detected on endoscopy, resulting in improved histopathological findings and serological markers.

A woman in her 40s visited our hospital for further examination of microcytic anemia (red blood cell count, 3.93 × 10⁶/µL; hemoglobin, 8.1 g/dL; mean corpuscular volume, 68.7 fL) and underwent esophagogastroduodenoscopy (EGD) in March 2019. Serum iron (11 µg/dL) and ferritin (7 ng/mL) levels were low, but vitamin B12 (431 pg/mL) was normal. The patient had never taken a proton-pump inhibitor. EGD showed extensive mucosal atrophy with marked vascular visibility in the entire area of the corpus except for the fornix, in which remnant oxyntic mucosa with diffuse redness and pseudopolyp-like lesions were observed (Fig. 1). The antrum was slightly atrophic. She was suspected of having AIG coexisting with an active H. pylori infection. This was confirmed by a strongly positive (1:160) anti-parietal cell antibody (PCA) test (indirect immunofluorescence method) and serum anti-H. pylori antibody (15.5 U/mL, enzyme immunoassay method) and H. pylori stool antigen (enzyme immunoassay method) tests; serum gastrin levels (radioimmunoassay method) were high (638 pg/mL) (Table 1). She received oral iron supplementation and eradication therapy for H. pylori.

In January 2020 (7 months after eradication therapy), another EGD showed reduced vascular visibility in the greater curvature of the middle to upper corpus (Fig. 2a), in addition to disappearance of diffuse redness in the fornix. PCA titers had decreased but remained positive (1:40) (Table 1). A biopsy specimen taken from the greater curvature of the middle corpus revealed basal-predominant dense lymphocytic infiltration of the lamina propria, resulting in obscured architecture of the fundic glands (Fig. 2b). Degeneration and pseudohypertrophy of parietal cells, a decrease in the number of chief cells, and foveolar hyperplasia were observed. Neither neutrophil infiltration nor intestinal metaplasia was observed. Degeneration of parietal cells and destruction of chief cells were illustrated by immunostaining for H⁺/K⁺-ATPase and pepsinogen I (PGI) (Fig. 2c, d). PGI-positive/MUC6-positive pseudopyloric metaplasia was observed (Fig. 2d, e). Linear hyperplasia of enterochromaffin-like cells was demonstrated by chromogranin A immunostaining (Fig. 2f). These serological and histopathological findings indicated that AIG persisted. Successful eradication was confirmed by a decrease in the serum anti-H. pylori antibody (5.1 U/mL) titer and the absence of H. pylori on immunohistochemical staining of a biopsy specimen.

Follow-up EGDs and serological tests were conducted in December 2020 and August 2021. PCA titers had declined further (1:20 and 1:20, respectively), and serum gastrin levels returned to normal (68 pg/mL and 64 pg/mL, respectively) (Table 1). EGDs showed reduced gastric atrophy in the greater curvature of the middle to upper corpus (Fig. 3a). A follow-up biopsy from the greater curvature of the middle corpus was performed in August 2021, 26 months post eradication. Recovery of the architecture of the fundic glands and regression of lymphocytic infiltration were revealed (Fig. 3b). Parietal and chief cells had recovered, as demonstrated by immunostaining for H⁺/K⁺-ATPase and PGI (Fig. 3c, d). PGI-negative/MUC6-positive pyloric metaplasia was observed (Fig. 3d, e). Chromogranin A immunostaining revealed reduced enterochromaffin-like cell hyperplasia (Fig. 3f). Neither intestinal metaplasia nor pancreatic acinar metaplasia was detected. These findings indicated that regression of gastric atrophy associated with AIG and partial recovery of fundic glands were ongoing after H. pylori eradication.

The first EGD in 2019 showed corpus-predominant advanced gastric atrophy and diffuse redness in the remnant oxyntic mucosa. Diagnosis of AIG was confirmed by the high PCA titer and hypergastrinemia. A diagnosis of active H. pylori infection was made based on positivity for serum anti-H. pylori antibodies and stool H. pylori antigen. Regression of AIG after eradication was indicated by improvement of gastric atrophy on follow-up EGDs and evidenced by histopathological recovery of the fundic glands, as well as reduced PCA titers and serum gastrin levels (Table 1).

A majority of AIG patients are infected with H. pylori before the development of gastric atrophy, and AIG progression is accompanied by a decrease or disappearance of H. pylori[10, 11]. However, the detection of AIG with ongoing gastric atrophy in a background of active H. pylori gastritis is difficult, as reported in a previous case report [12]. In our case, it is possible that AIG, initially masked by active H. pylori gastritis, progressed and only became noticeable at presentation, although there are insufficient data to confirm this.

Conflicting results have been presented regarding the effects of H. pylori eradication on H. pylori-positive AIG. One study reported that eradication led to healing of active gastritis in 80% of patients with non-atrophic H. pylori-positive AIG [5], whereas a previous case report showed rapid progression of gastric atrophy after eradication in a patient with H. pylori-positive AIG [9], supporting a hypothesis that H. pylori infection inhibits development of AIG (based on experimental data from a murine model) [8]. Another case report showed that early-stage AIG appeared after eradication of H. pylori in a patient with active H. pylori gastritis [12]. Other studies reported reversal of gastric atrophy after eradication in 20% of patients with H. pylori-positive AIG, while gastric atrophy was persistent at long-term follow-up in the remaining 80% [6, 7]. The presence of mild atrophy and moderate-severe inflammation and the absence of intestinal metaplasia are histopathological factors predictive of improvement of gastric atrophy [7]. Histopathological findings from the first biopsy in our case showed these predictive factors.

There are two types of pyloric gland-like metaplasia that occur to compensate for oxyntic mucosal damage in chronic atrophic gastritis, such as H. pylori gastritis and AIG [13, 14], namely, PGI-positive/MUC6-positive pseudopyloric and PGI-negative/MUC6-positive pyloric metaplasia. Both types are characteristic features of AIG with advanced gastric atrophy. A few glands with pyloric gland-like metaplasia were observed in our case (Fig. 2,,3), suggesting regression of gastric atrophy after H. pylori eradication.

AIG is associated with an increased risk for two types of gastric neoplasm: adenocarcinoma and neuroendocrine tumor. Regarding gastric cancer in AIG, cancer risk is restricted to those with histologically high-risk stages of gastritis and is associated mainly with previous or current H. pylori infection [15, 16]. From the viewpoint of cancer prevention, it would be of great clinical importance to accurately identify AIG patients with active H. pylori infection before progression of gastric atrophy and to evaluate their histopathological findings after eradication. Patients with persistent gastric atrophy after eradication, along with intestinal metaplasia, should receive endoscopic surveillance.

In conclusion, endoscopic, serological, and histopathological findings demonstrated regression of gastric atrophy following eradication in a patient with AIG coexisting with active H. pylori infection. An accumulation of similar cases would help to clarify the exact link between active H. pylori infection and development of AIG. Follow-up of such cases would provide further information about the long-term effects of eradication on cancer risk in patients with AIG. The CARE Checklist has been completed by the authors for this case report, attached as supplementary material (for all online suppl. material, see www.karger.com/doi/10.1159/000528388).

The authors would like to thank Patrick Hughes (Bioedit Limited) for language editing.

The study complies with the provisions of the Declaration of Helsinki. Informed written consent was obtained from the patient prior to publication of the report and any accompanying images. The study protocol was reviewed, and the need for approval was waived by the Ethics Committee of the Uji-Tokushukai Medical Center.

The authors have no conflicts of interest to declare.

The authors declare that there were no funding sources for this study.

T.K. wrote the draft of this manuscript. Y.N. and T.K. acquired the data. R.K. analyzed the pathological findings. K.H. supervised the case report. All the authors have read and approved the final version of the manuscript.

All data analyzed during the study are included in this article. Inquiries can be sent to the corresponding author.