최신연구결과(해외)

General studyLong-term natural history of autoimmune gastritis: results from a prospective, monocentric series

관리자
2023-12-18
조회수 243

Am J Gastroenterol. 2023 Dec 5. doi: 10.14309/ajg.0000000000002619. 


Introduction 

* Despite the recent MAPS guidelines recommend a follow-up screening endoscopy with biopsies every 3 to 5 years, the magnitude of the risk of developing gastric neuroendocrine tumors (NET) and epithelial dysplasia/neoplasia has been recently questioned, and this has raised a stimulating debate.

* Particularly, while the risk of developing NET is well established, the risk of developing gastric epithelial neoplasia seems to be virtually zero in highly selected AIG patients, all displaying circulating anti-parietal cells antibodies (PCA), and with no history of H. pylori infection.

 * The aims of this prospective study were to characterize the clinical clusters of AIG patients and their histopathological evolution through disease stages, from the potential to the complicated one. 

 

Methods

* We enrolled all consecutive outpatients who had been diagnosed with any AIG stage between January 2000 and December 2022, thus extending the overall length of the follow-up, and the previous enrolment of five years (since January 2018 onwards).

* Potential AIG was defined as the presence of circulating PCA, in the absence of current H. pylori infection, and in the absence of gastric histopathological atrophy (at any site).

* The diagnosis of overt AIG (from early to complicated stage) was based on histopathology, by assessing gastric biopsies from the antrum, corpus and incisura angularis, following the updated Sydney System criteria.

* The first time point (T0) was considered that of the first histopathological proof of AIG, or the first occurrence of PCA in patients later classified as potential AIG.

* The whole AIG spectrum was further divided into five stages.

- Potential AIG (stage 0; PCA positive and no metaplasia or atrophy)

- Early stage (stage 1; lymphocytic and plasma cell infiltration, mild atrophy in the oxyntic mucosa)

- Florid stage (stage 2; lymphocytic and plasma cell infiltration, moderate atrophy in the oxyntic mucosa)

- End stage (stage 3; severe atrophy of the oxyntic mucosa)

- Complicated stage (stage 4; ECL cell dysplasia, type I NET, low‐ grade or high‐grade non‐endocrine dysplasia/glandular intraepithelial neoplasia, or adenocarcinoma)


<Demographic and laboratory data>

* In all cases, active H. pylori infection was excluded by means of antigen stool test (Biohit HealthCare, Milan, Italy), as well as by histopathology.

* We did not exclude a priori those AIG patients who had a known history of eradicated H. pylori infection.  


<Clinical clusters>

* We have categorized all these into seven different clinical clusters.

1) incidental histopathological finding at endoscopy performed for reasons other than AIG

2) hematological findings (i.e., anemia, macrocytosis, anisocytosis, pancytopenia) 

3) persistence of anemia in celiac disease patients on a gluten-free diet 

4) serological screening in patients with other autoimmune diseases (i.e., autoimmune thyroid disease, vitiligo, type I diabetes mellitus, Addison’s disease, rheumatoid arthritis, connective tissue disease, psoriasis) 

5) first-degree family history of AIG

6) infertility or obstetric complications (also including miscarriage, pre-term delivery, failure of assisted reproductive technologies, neural tube defects in the fetus)  

7) neuropsychiatric manifestations (i.e., ataxia, impaired vibration sense, paresthesia, mood disorders, psychosis, memory loss, foggy mind, fatigue)


<Histopathological features>

* Metaplasia: mild, moderate and severe

* Atrophy (loss of glands appropriate to the gastric mucosa, including both glandular loss and metaplastic (pseudopyloric and/or intestinal) transformation of the native glands): mild (<30% of the specimens from the same compartment), moderate (31%‐60%) or severe (>60%) 

* Antral gastrin cell hyperplasia and corpus‐fundus enterochromaffin-like (ECL) cell proliferation were recorded.

* Presence of exocrine/adenomatous or neuroendocrine gastric dysplasia, adenocarcinoma, and type I NET 


Results 

* The flowchart of the study is depicted in Figure 1.

* Maximum disease duration (i.e., from the first diagnosis of AIG to the last follow-up) was 27 years (median 18 years, IQR 14-23) / Overall median prospective follow-up was 52 months (IQR 12- 95)

* 24 patients (median age 57 years, F/M ratio 2.5:1) had a certain H. pylori infection that had been eradicated before entering the study.  

Figure 1. Flowchart of the study. Twenty-two patients were excluded, according to the study design. The patients included were 498, of whom 93 were potential autoimmune gastritis (AIG), 63 had an early stage at T0, 64 had a florid stage and 263 had an end stage. In addition, 15 patients had a complication at diagnosis (NET G1 in seven patients and dysplasia in eight patients).

<Figure 2>

* No clear variation trend was observed for overall chromogranin A and PCA, while gastrin-17 tended to increase over time.

* Across stages, chromogranin A did not variate, while gastrin-17 tended to increase only in stage 0 patients, as a proof of their evolution into overt AIG (i.e., stages from 1 to 4). Instead, within the other stages, gastrin-17 tended to be stable over time. 

Figure 2. Plots showing the changes over time of the serum chromogranin A, plasma gastrin-17, and serum anti-parietal cell antibodies (PCA) (upper row), and according to the different disease stages (lower row). 


Figure 3. (A) Kaplan Meier worsening-free survival estimates, overall (left) and by disease stage (right). (B) Stage 4 worsening-free Kaplan Meir survival estimates, overall (left) and by disease stage (right). 


Figure 4. Stage 0 worsening-free Kaplan Meir survival estimates, overall (left), and by male sex (right) 


* Overt AIG (405 patients) at the time of the enrolment (T0) 63 (15.6%) patients were classified as stage 1, 64 (15.8%) as stage 2, 263 (64.9%) as stage 3, and 15 (3.7%) as stage 4. (Table 1)

Table 1. Demographic and laboratory variables of all patients included in the study at the time of the enrolment.


* Clinical suspicion of AIG was based on seven clinical clusters that led to diagnosis, as reported in Table 2.

Table 2. Demographic characteristics and disease stage according to the different clinical clusters. 


<Abstract>

Objectives: The natural history of autoimmune gastritis (AIG) has been poorly described. We herein report the long-term natural history and clinical clustering of the full spectrum of AIG, from the potential to the complicated stage.

Methods: Prospective, single-center study conducted in a tertiary referral center. AIG patients at any stage (0=potential; 1=early; 2=florid; 3=severe; 4=complicated) were enrolled (January 2000-December 2022). The histopathological evolution, the clinical presentation, and the correlates of evolution of potential AIG were assessed.

Results: 498 AIG patients (mean age 56.7±15.2, F:M ratio 2.5:1) were included, of whom 93 with potential AIG. The maximum disease duration was 27 years (median 18, IQR 14-23), while the overall median follow-up was 52 months (IQR 12-95). Age was significantly lower in stage 0 compared to the other stages. Accidental histologic evidence and hematologic findings were the most common clusters of diagnosis. The overall median rate of progression was 7.29 per 100 person/year (95% CI 6.19-8.59), while the stage-specific rates of progression were 10.85 (stage 0; 95% CI 7.75-15.18), 14.83 (stages 1-2; 95% CI 11.89-18.49), and 2.68 (stage 3; 95% CI 1.88-3.84). Newly onset neoplastic complications at follow-up occurred in 41/483 patients (8.5%; 23 neuroendocrine tumors, 18 epithelial dysplasia). No cases of adenocarcinoma were noticed. Male sex was associated with a greater likelihood of evolving from potential AIG to overt AIG.

Conclusions: AIG is a progressive disorder, with a virtually absent risk of gastric adenocarcinoma. Potential AIG patients should be monitored as they carry a high risk of evolving into overt AIG.

Keywords: anemia; dysplasia; gastric atrophy; neuroendocrine tumor; potential; vitamin B12

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대한자가면역성위염연구회

주소 : 경기도 용인시 기흥구 중부대로 579, 508-23호 (구갈동, 강남대프라자)

대표전화 : 070-8080-0453  이메일 : autogastritis@gmail.com 


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