<5. AIG: Autoimmune gastritis>
The worldwide impact of immune-mediated disorders is rising in parallel with the declining incidence of infectious diseases. The hygiene hypothesis postulates a relationship between these two simultaneous epidemiological trends. The expanding knowledge on the complex interplay between environmental and host-related aetiopathogenetic machinery, our growing understanding of the microbiota and evidence of gene–environment interactions suggest new interesting pathogenetic speculations.
AIG is viewed as the prototype of host-related gastric inflammatory conditions. The oxyntic–parietal autoantigen restricts the immune-mediated inflammatory lesions to the oxyntic (ie, corpus/fundus) gastric compartment. Thus, the pathogenetic mechanisms of AIG spare the mucosecreting mucosa. When antral inflammatory and atrophic lesions coexist with AIG, they are the result of comorbidities, particularly previous or current H. pylori infection. It has also been suggested that antigenic mimicry between bacterial and parietal cell autoantigens may aetiologically link AIG to previous or current H. pylori infection (so-called ‘secondary AIG’).
The initial immune-mediated inflammation of the oxyntic mucosa (ie, non-atrophic AIG) usually progresses to mucosal atrophy, featuring a topographical phenotype and giving rise to specific serological responses. Oxyntic atrophy results in a progressive decrease of acid secretion, which triggers the hyperplastic modulation of ECL and may develop into type 1 NET (see section 2.1.4). The significantly increased risk of neuroendocrine neoplasia supports the need for surveillance of patients with atrophic AIG.
"AIG는 parietal cell을 타겟으로 스스로 조절되지 않는 면역 매개 질환이다. 염증과 위축은 oxyntic mucosa에만 국한되며, 진행 단계에서는 위산 분비 저하로 인한 기능적 문제가 발생한다."
<Comment>
The topography of the target autoantigen restricts the inflammatory lesions to the oxyntic mucosa; less frequently, due to the variable distal extension of native oxyntic glands, the inflammation also extends distally to the incisura angularis.
Pathogenesis of ‘primary AIG’ are still unclear !!
Major target autoantigen: gastric proton pump H+/K+ATPase and its α and β subunits, which are targeted by both anti-parietal cell autoantibodies (PCA) and autoreactive T cells. The exact trigger for the expansion of these autoreactive clones is unknown.
The marker of the disease is its histologically documented restriction to the oxyntic mucosa (figure 9).
Figure 9. Autoimmune gastritis: atrophic phase. (A) Antral mucosa in autoimmune gastritis: the native mucosecreting mucosa is easily recognisable. In this case, the absence of any inflammatory involvement coexists with elongated foveolae and smooth muscle hyperplasia (spindle cells interposed to the glandular units). Both features are characteristic of reactive gastropathy, which often coexists with oxyntic autoimmune disease (H&E; original magnification 20×). (B) Atrophic oxyntic mucosa with mononuclear inflammatory infiltrate. The lamina propria is expanded by fibrosis and inflammatory cells. Intestinalised and pseudopyloric metaplastic glandular units replace the tubular native glands. Intestinalised cells mostly feature complete-type intestinal metaplasia (H&E; original magnification 20×). (C) Oxyntic mucosa biopsy specimen stained with anti-chromogranin A antibodies for enterochromaffin-like cells, showing nodular hyperplasia (immunostain for chromogranin A; original magnification 10×).
The diagnosis of AIG is achieved by serology (autoantibodies against PCA and AIFA, Pgs as markers of advanced atrophy and gastrin-17), gastroscopy and the characteristic histological findings (see sections 2.5.3 and 2.5.4). Gastric hypoacidity results in loss of intrinsic factor, with iron and vitamin B12 malabsorption and eventually pernicious megaloblastic anaemia (see section 2.5.5). Micronutrient malabsorption favours the occurrence of life-threatening and irreversible complications.
"AIG의 유병률은 다양하며 특히, 서양 인구에서 높은 것 같다. 하지만, 이러한 추세는 현재 또는 이전의 H. pylori 동반 여부를 제외하고 잘 설계된 인구 기반 연구를 통해 확인되어야 한다. AIG에 대한 부담은 방법론적인 문제 (methodological issues)로 인해 제대로 평가하기가 어렵다는 것이다."
<Comment>
AIG 확진을 위해서는 내시경을 통한 조직검사가 필요하므로 large population-based studies 는 거의 불가능하며, 이를 대신하는 여러 다른 marker 들인 PCA (potentially declining in the advanced stage of oxyntic atrophy) and intrinsic factor (AIFA), serum Pgs, gastrin levels 이 사용되고 있습니다. 하지만, Studies based on the prevalence of cobalamin levels and pernicious anaemia (both late manifestations) 는 매우 낮은 sensitivity를 갖기 때문에 진행하기 어렵습니다.
이러한 방법론적인 불일치가 있지만, AIG의 유병률은 0.1% ~ 2% (in the general population)을 보이고 있고, 60세 이상, 여성에서 높은 것으로 알려져 있습니다.
The data on the prevalence of AIG obtained in different studies and the diagnostic criteria used are summarised in table 4.
Table 4. Summary of the results of the studies on the prevalence of autoimmune gastritis (AIG)
* AIG is not believed to be associated with gastric carcinoma, except in the presence of a cancer risk ‘expansion’ due to concurrent or previous H. pylori infection. There is, however, a distinct risk for gastric NET related to the sustained increase in serum gastrin.
"자가면역 위축성 위염은 내시경, 조직병리학적, 혈청학적 데이터를 바탕으로 진단 (high degree of confidence) 할 수 있다."
<Comment>
* Non-atrophic stages: clinical signs과 symptoms이 뚜렷하지 않기 때문에 인식하기 쉽지 않습니다.
* Atrophic stages: clinical manifestations, including comorbidities (serological, endoscopic & histopathological abnormalities와 같은)으로 진행되며 나타납니다.
* 가장 sensitive serum test는 PCA에 대한 antibiodies를 확인 하는 것입니다. 그러나, 나이가 들수록 줄어들 수 있지만 APCA가 없다고 하여 AIG를 배제할 수는 없습니다. 또한, AIFA의 확인은 (진단 시 low Pg 또는 high gastrinemia와 함께 하더라도) sensitivity 및 specificity가 낮아서, endoscopic 및 histopathological findings을 같이 이용해서 진단에 활용해야 합니다 (see section 2.5.5). 최근 prospective multicentre cohort study에서는 low Pg levels이 autoantibodies보다 AIG 진단에 있어 보다 sensitive 하였음을 보고하였습니다. (최신연구결과(해외) 57번: Chapelle N, Martin J, Osmola M, et al. Serum pepsinogens can help to discriminate between h. pylori-induced and auto-immune atrophic gastritis: results from a prospective multicenter study. Dig Liver Dis 2023;55:1345–51.)
* In a cross-sectional study of 210 patients with AIG undergoing surveillance gastroscopy with NBI, EGGIM staging detects oxyntic IM with high sensitivity (91.5%, 95% CI: 86.1% to 95.3%) but low specificity (21.7%, 95% CI: 10.9% to 36.4%). This finding has been interpreted as being related to the NBI overassessment of IM when only pseudopyloric metaplasia is already established.
* Histological findings of AIG: Loss of native oxyntic glands accompanied by mononuclear infiltrate and replacement by micro-scars of inflamed fibrous tissue (ie, non-metaplastic atrophy)
* Disappearance of oxyntic glands coexists with two types of metaplastic transformation:
(1) pseudopyloric metaplasia as phenotypical change covering the molecular profiles belonging to pyloric metaplasia, ulcer-associated cell lineage and spasmolytic polypeptide-expressing metaplasia (SPEM)
(2) IM, in all its phenotypical and molecular subtypes (IM mainly exibits complete phenotype (see section 2.4.6))
* Atrophic AIG (also referred as ‘florid phase’) commonly features hyperplastic polypoid lesions (rarely associated with pyloric gland adenomas) and either linear or nodular hyperplasia of the ECL cells (figure 9).
"일부 환자 군에서 H. pylori가 자가면역 과정을 유발하여 oxyntic mucosa의 위축을 초래할 수 있다고 가정한다."
<Comment>
Solid evidence confirms that primary AIG (ie, unrelated to H. pylori) is a real nosological (질병분류학) entity. AIG is far more prevalent in patients with autoimmune thyroid disease, Addison’s disease, vitiligo, coeliac disease and other autoimmune disorders, and in those displaying the HLA-DRB1*03 and HLA-DRB1*04 haplotypes, commonly associated with autoimmunity.
The role of H. pylori in the pathogenesis of AIG is still debated,but there is some evidence that in a subset of patients, H. pylori may trigger the autoimmune process leading to atrophy of the oxyntic mucosa (ie, ‘secondary’ AIG). This may be due to the cross-reactivity between H. pylori-induced antibodies and proton pump antigens in the parietal cells of oxyntic mucosa (ie, antigenic mimicry).
According to this theory, at least in a subset of cases, H. pylori may act as a trigger of the inflammatory process by shifting towards the non-self-limiting autoimmune destruction of the oxyntic mucosa.
--> 제 견해이긴 하지만, H. pylori는 AIG 유발 인자라기 보다 AIG process와 함께 oxyntic mucosa의 destruction을 악화시키고, atrophy를 진행시키며, carcinogenesis를 유발하는 동반 질환으로 생각하는 것이 맞지 않을까 싶습니다.
"AIG의 진단은 위 내시경으로 이루어지며, 전형적인 조직학적 소견을 보여주는 유문부와 체부에서 별도로 채취한 생검을 통해 진단한다. AIG에 대한 가장 민감한 혈청 검사는 벽세포(PCA)에 대한 항체를 검출하는 것이다."
<Comment>
In the earliest phase of non-atrophic AIG, all mucosal compartments may appear endoscopically normal.
In the subsequent atrophic phase, endoscopy shows oxyntic (ie, fundic and corpus) atrophy, loss of gastric folds, pale and thin mucosa rendering submucosal capillary vessels visible.
When using the Kimura-Takemoto classification, East Asian endoscopists include atrophic AIG in the O3 category. The O3 category, however, implies antral atrophic involvement, which is absent in primary AIG (figures 3 and 5). (개인적인 생각이지만 결국, 새로운 분류법이 따로 설정되어야 할 것 같습니다.)
In the absence of previous or current H. pylori comorbidity, the antral mucosecreting compartment may be endoscopically normal or erythematous when reactive gastropathy is present (tables 1 and 5).
Table 5. Characteristic features of DIG (drug-induced gastritis) associated with medications 
Oxyntic inflammation and atrophy are associated with a spectrum of ECL cell hyperplastic changes, ranging from linear and nodular hyperplasia to a neoplastic progression to type 1 NET (see section 2.5.3).
In patients with AIG, the role of OLGA/ OLGIM in the prediction of epithelial gastric neoplastic lesions should be further evaluated. Because primary AIG spares the antrum, the OLGA stage in these patients is never higher than stage II. Stages III–IV strongly suggest prior H. pylori infection that has resulted in antral atrophic lesions (see section 2.5.7). In these patients with AIG with high OLGA stages (related to the effects of H. pylori), the risk of gastric neoplasia has been estimated to range between 6.3% and 25%.
--> Primary AIG는 antrum을 sparing 하기 때문에 OLGA stage는 II 이상 나올 수가 없습니다. 새로운 atrophic gastritis에 대한 staging system이 필요할 것으로 보입니다.
Due to the absence or paucity of symptoms in the early stages of AIG, a substantial diagnostic delay (상당한 진단의 지연) may result in the development of life-threatening and irreversible complications. Micronutrient malabsorption in AIG is responsible for the wide spectrum of clinical manifestations in advanced disease (see section 2.5.3).
"PgI 및 PgI/II 비율과 혈청 가스트린-17 의 측정은 AIG의 진행성 위축 단계를 선별할 때 가장 정확한 혈청학적 테스트이다."
<Comment>
The British Society of Gastroenterology에서는 gastric adenocarcinoma의 incidence가 낮은 지역(such as UK)에서 screening tools로써 biomarkers의 사용을 권고 하였습니다. (Banks M, Graham D, Jansen M, et al. British society of gastroenterology guidelines on the diagnosis and management of patients at risk of gastric adenocarcinoma. Gut 2019;68:1545–75.)
The biomarkers serum PgI and II levels, the PgI/II ratio, serum gastrin-17 and H. pylori serology have long been measured and explored, alone or in combination, to detect advanced or late-stage atrophic gastritis. Low serum PgI and a low PgI/II ratio can provide a non-invasive diagnosis of advanced stage atrophic gastritis, and, importantly when H. pylori serology is also negative, endoscopy is recommended by the MAPS II Guideline Update 2019.
* Observational study (screening tests in 28 Japanese patients with confirmed histological AIG)
: 78.6% positive predictive value / (1) Serum gastrin >172pg/mL, (2) PgI: 14.5ng/dL, (3) PgI/II ratio: 2.1
* Non-invasive biomarkers를 이용한 AIG 환자의 prospective study 들이 적절한 long-term management를 결정하기 위해 서둘러 필요하겠습니다.
"AIG 환자에서는 내시경 감시를 고려해야 하며, 제한된 데이터 이자만, 3~5년 간격을 제안한다."
<Comment>
AIG-associated gastric cancer risk에 대한 과거 연구결과들은 preneoplastic gastric conditions (see section 2.1.4)인 pernicious anaemia를 포함 하고 있었으며, 이러한 연구들의 대부분은 H. pylori infection에 노출되었거나 가능성 있는 다수의 환자들이 포함되어 있었습니다. H.pylori의 과거 감염이나 현재 감염은 pangastritis atrophy를 유발하고, cancer promoting cofactor로써 작용하며, 결국 AIG-linked cancer risk로 언급하기에는 제한점이 있습니다 (figure 3).
최근 연구에 따르면, H. pylori infection과 동반되지 않은 AIG에서 gastric cancer risk를 평가할 때 정상 mucosecreting antrum (normal antral mucosa, only reactive gastropathy)이 필요하다는 내용은 위암 발생을 용이하게 하는 microenvironment에서 H. pylori의 영향을 배제하는데 타당할 것 같은 내용으로 보입니다. (Rugge M, Genta RM, Malfertheiner P, et al. Atrophic autoimmune gastritis: ’a muddled or misguided core concept compromises our overall comprehension of the problem’ Gut 2023;73:207–8.)
The risk of neuroendocrine neoplasia in AIG is related to the increase of serum gastrin (as a proxy for oxyntic atrophy) promoting ECL proliferation and potentially resulting in type I NETs (also referred to as gastric carcinoids). The optimal interval for AIG endoscopic surveillance has not been agreed upon. One small prospective study concluded that four yearly intervals were safe and sufficient to detect early neoplastic mucosal lesions (Lahner E, Caruana P, D’Ambra G, et al. First endoscopic-histologic follow-up in patients with body-predominant atrophic gastritis: when should it be done. Gastrointest Endosc 2001;53:443–8.).
Based on the available data on the negligible risk of gastric malignancies associated with primary AIG, an interval of 3–5years endoscopy and biopsy follow-up is suggested, more tailored for the early detection of NETs rather than for gastric cancer secondary prevention. (위 내시경의 주기는 gastric cancer 2차 예방 보다는 NETs의 조기 발견에 촛점을 두어 결정하는 것이 합당할 것으로 보여 집니다.)
<5. AIG: Autoimmune gastritis>
The worldwide impact of immune-mediated disorders is rising in parallel with the declining incidence of infectious diseases. The hygiene hypothesis postulates a relationship between these two simultaneous epidemiological trends. The expanding knowledge on the complex interplay between environmental and host-related aetiopathogenetic machinery, our growing understanding of the microbiota and evidence of gene–environment interactions suggest new interesting pathogenetic speculations.
AIG is viewed as the prototype of host-related gastric inflammatory conditions. The oxyntic–parietal autoantigen restricts the immune-mediated inflammatory lesions to the oxyntic (ie, corpus/fundus) gastric compartment. Thus, the pathogenetic mechanisms of AIG spare the mucosecreting mucosa. When antral inflammatory and atrophic lesions coexist with AIG, they are the result of comorbidities, particularly previous or current H. pylori infection. It has also been suggested that antigenic mimicry between bacterial and parietal cell autoantigens may aetiologically link AIG to previous or current H. pylori infection (so-called ‘secondary AIG’).
The initial immune-mediated inflammation of the oxyntic mucosa (ie, non-atrophic AIG) usually progresses to mucosal atrophy, featuring a topographical phenotype and giving rise to specific serological responses. Oxyntic atrophy results in a progressive decrease of acid secretion, which triggers the hyperplastic modulation of ECL and may develop into type 1 NET (see section 2.1.4). The significantly increased risk of neuroendocrine neoplasia supports the need for surveillance of patients with atrophic AIG.
"AIG는 parietal cell을 타겟으로 스스로 조절되지 않는 면역 매개 질환이다. 염증과 위축은 oxyntic mucosa에만 국한되며, 진행 단계에서는 위산 분비 저하로 인한 기능적 문제가 발생한다."
<Comment>
The topography of the target autoantigen restricts the inflammatory lesions to the oxyntic mucosa; less frequently, due to the variable distal extension of native oxyntic glands, the inflammation also extends distally to the incisura angularis.
Pathogenesis of ‘primary AIG’ are still unclear !!
Major target autoantigen: gastric proton pump H+/K+ATPase and its α and β subunits, which are targeted by both anti-parietal cell autoantibodies (PCA) and autoreactive T cells. The exact trigger for the expansion of these autoreactive clones is unknown.
The marker of the disease is its histologically documented restriction to the oxyntic mucosa (figure 9).
Figure 9. Autoimmune gastritis: atrophic phase. (A) Antral mucosa in autoimmune gastritis: the native mucosecreting mucosa is easily recognisable. In this case, the absence of any inflammatory involvement coexists with elongated foveolae and smooth muscle hyperplasia (spindle cells interposed to the glandular units). Both features are characteristic of reactive gastropathy, which often coexists with oxyntic autoimmune disease (H&E; original magnification 20×). (B) Atrophic oxyntic mucosa with mononuclear inflammatory infiltrate. The lamina propria is expanded by fibrosis and inflammatory cells. Intestinalised and pseudopyloric metaplastic glandular units replace the tubular native glands. Intestinalised cells mostly feature complete-type intestinal metaplasia (H&E; original magnification 20×). (C) Oxyntic mucosa biopsy specimen stained with anti-chromogranin A antibodies for enterochromaffin-like cells, showing nodular hyperplasia (immunostain for chromogranin A; original magnification 10×).
The diagnosis of AIG is achieved by serology (autoantibodies against PCA and AIFA, Pgs as markers of advanced atrophy and gastrin-17), gastroscopy and the characteristic histological findings (see sections 2.5.3 and 2.5.4). Gastric hypoacidity results in loss of intrinsic factor, with iron and vitamin B12 malabsorption and eventually pernicious megaloblastic anaemia (see section 2.5.5). Micronutrient malabsorption favours the occurrence of life-threatening and irreversible complications.
"AIG의 유병률은 다양하며 특히, 서양 인구에서 높은 것 같다. 하지만, 이러한 추세는 현재 또는 이전의 H. pylori 동반 여부를 제외하고 잘 설계된 인구 기반 연구를 통해 확인되어야 한다. AIG에 대한 부담은 방법론적인 문제 (methodological issues)로 인해 제대로 평가하기가 어렵다는 것이다."
<Comment>
AIG 확진을 위해서는 내시경을 통한 조직검사가 필요하므로 large population-based studies 는 거의 불가능하며, 이를 대신하는 여러 다른 marker 들인 PCA (potentially declining in the advanced stage of oxyntic atrophy) and intrinsic factor (AIFA), serum Pgs, gastrin levels 이 사용되고 있습니다. 하지만, Studies based on the prevalence of cobalamin levels and pernicious anaemia (both late manifestations) 는 매우 낮은 sensitivity를 갖기 때문에 진행하기 어렵습니다.
이러한 방법론적인 불일치가 있지만, AIG의 유병률은 0.1% ~ 2% (in the general population)을 보이고 있고, 60세 이상, 여성에서 높은 것으로 알려져 있습니다.
The data on the prevalence of AIG obtained in different studies and the diagnostic criteria used are summarised in table 4.
Table 4. Summary of the results of the studies on the prevalence of autoimmune gastritis (AIG)
* AIG is not believed to be associated with gastric carcinoma, except in the presence of a cancer risk ‘expansion’ due to concurrent or previous H. pylori infection. There is, however, a distinct risk for gastric NET related to the sustained increase in serum gastrin.
"자가면역 위축성 위염은 내시경, 조직병리학적, 혈청학적 데이터를 바탕으로 진단 (high degree of confidence) 할 수 있다."
<Comment>
* Non-atrophic stages: clinical signs과 symptoms이 뚜렷하지 않기 때문에 인식하기 쉽지 않습니다.
* Atrophic stages: clinical manifestations, including comorbidities (serological, endoscopic & histopathological abnormalities와 같은)으로 진행되며 나타납니다.
* 가장 sensitive serum test는 PCA에 대한 antibiodies를 확인 하는 것입니다. 그러나, 나이가 들수록 줄어들 수 있지만 APCA가 없다고 하여 AIG를 배제할 수는 없습니다. 또한, AIFA의 확인은 (진단 시 low Pg 또는 high gastrinemia와 함께 하더라도) sensitivity 및 specificity가 낮아서, endoscopic 및 histopathological findings을 같이 이용해서 진단에 활용해야 합니다 (see section 2.5.5). 최근 prospective multicentre cohort study에서는 low Pg levels이 autoantibodies보다 AIG 진단에 있어 보다 sensitive 하였음을 보고하였습니다. (최신연구결과(해외) 57번: Chapelle N, Martin J, Osmola M, et al. Serum pepsinogens can help to discriminate between h. pylori-induced and auto-immune atrophic gastritis: results from a prospective multicenter study. Dig Liver Dis 2023;55:1345–51.)
* In a cross-sectional study of 210 patients with AIG undergoing surveillance gastroscopy with NBI, EGGIM staging detects oxyntic IM with high sensitivity (91.5%, 95% CI: 86.1% to 95.3%) but low specificity (21.7%, 95% CI: 10.9% to 36.4%). This finding has been interpreted as being related to the NBI overassessment of IM when only pseudopyloric metaplasia is already established.
* Histological findings of AIG: Loss of native oxyntic glands accompanied by mononuclear infiltrate and replacement by micro-scars of inflamed fibrous tissue (ie, non-metaplastic atrophy)
* Disappearance of oxyntic glands coexists with two types of metaplastic transformation:
(1) pseudopyloric metaplasia as phenotypical change covering the molecular profiles belonging to pyloric metaplasia, ulcer-associated cell lineage and spasmolytic polypeptide-expressing metaplasia (SPEM)
(2) IM, in all its phenotypical and molecular subtypes (IM mainly exibits complete phenotype (see section 2.4.6))
* Atrophic AIG (also referred as ‘florid phase’) commonly features hyperplastic polypoid lesions (rarely associated with pyloric gland adenomas) and either linear or nodular hyperplasia of the ECL cells (figure 9).
"일부 환자 군에서 H. pylori가 자가면역 과정을 유발하여 oxyntic mucosa의 위축을 초래할 수 있다고 가정한다."
<Comment>
Solid evidence confirms that primary AIG (ie, unrelated to H. pylori) is a real nosological (질병분류학) entity. AIG is far more prevalent in patients with autoimmune thyroid disease, Addison’s disease, vitiligo, coeliac disease and other autoimmune disorders, and in those displaying the HLA-DRB1*03 and HLA-DRB1*04 haplotypes, commonly associated with autoimmunity.
The role of H. pylori in the pathogenesis of AIG is still debated,but there is some evidence that in a subset of patients, H. pylori may trigger the autoimmune process leading to atrophy of the oxyntic mucosa (ie, ‘secondary’ AIG). This may be due to the cross-reactivity between H. pylori-induced antibodies and proton pump antigens in the parietal cells of oxyntic mucosa (ie, antigenic mimicry).
According to this theory, at least in a subset of cases, H. pylori may act as a trigger of the inflammatory process by shifting towards the non-self-limiting autoimmune destruction of the oxyntic mucosa.
--> 제 견해이긴 하지만, H. pylori는 AIG 유발 인자라기 보다 AIG process와 함께 oxyntic mucosa의 destruction을 악화시키고, atrophy를 진행시키며, carcinogenesis를 유발하는 동반 질환으로 생각하는 것이 맞지 않을까 싶습니다.
"AIG의 진단은 위 내시경으로 이루어지며, 전형적인 조직학적 소견을 보여주는 유문부와 체부에서 별도로 채취한 생검을 통해 진단한다. AIG에 대한 가장 민감한 혈청 검사는 벽세포(PCA)에 대한 항체를 검출하는 것이다."
<Comment>
In the earliest phase of non-atrophic AIG, all mucosal compartments may appear endoscopically normal.
In the subsequent atrophic phase, endoscopy shows oxyntic (ie, fundic and corpus) atrophy, loss of gastric folds, pale and thin mucosa rendering submucosal capillary vessels visible.
When using the Kimura-Takemoto classification, East Asian endoscopists include atrophic AIG in the O3 category. The O3 category, however, implies antral atrophic involvement, which is absent in primary AIG (figures 3 and 5). (개인적인 생각이지만 결국, 새로운 분류법이 따로 설정되어야 할 것 같습니다.)
In the absence of previous or current H. pylori comorbidity, the antral mucosecreting compartment may be endoscopically normal or erythematous when reactive gastropathy is present (tables 1 and 5).
Table 5. Characteristic features of DIG (drug-induced gastritis) associated with medications
Oxyntic inflammation and atrophy are associated with a spectrum of ECL cell hyperplastic changes, ranging from linear and nodular hyperplasia to a neoplastic progression to type 1 NET (see section 2.5.3).
In patients with AIG, the role of OLGA/ OLGIM in the prediction of epithelial gastric neoplastic lesions should be further evaluated. Because primary AIG spares the antrum, the OLGA stage in these patients is never higher than stage II. Stages III–IV strongly suggest prior H. pylori infection that has resulted in antral atrophic lesions (see section 2.5.7). In these patients with AIG with high OLGA stages (related to the effects of H. pylori), the risk of gastric neoplasia has been estimated to range between 6.3% and 25%.
--> Primary AIG는 antrum을 sparing 하기 때문에 OLGA stage는 II 이상 나올 수가 없습니다. 새로운 atrophic gastritis에 대한 staging system이 필요할 것으로 보입니다.
Due to the absence or paucity of symptoms in the early stages of AIG, a substantial diagnostic delay (상당한 진단의 지연) may result in the development of life-threatening and irreversible complications. Micronutrient malabsorption in AIG is responsible for the wide spectrum of clinical manifestations in advanced disease (see section 2.5.3).
"PgI 및 PgI/II 비율과 혈청 가스트린-17 의 측정은 AIG의 진행성 위축 단계를 선별할 때 가장 정확한 혈청학적 테스트이다."
<Comment>
The British Society of Gastroenterology에서는 gastric adenocarcinoma의 incidence가 낮은 지역(such as UK)에서 screening tools로써 biomarkers의 사용을 권고 하였습니다. (Banks M, Graham D, Jansen M, et al. British society of gastroenterology guidelines on the diagnosis and management of patients at risk of gastric adenocarcinoma. Gut 2019;68:1545–75.)
The biomarkers serum PgI and II levels, the PgI/II ratio, serum gastrin-17 and H. pylori serology have long been measured and explored, alone or in combination, to detect advanced or late-stage atrophic gastritis. Low serum PgI and a low PgI/II ratio can provide a non-invasive diagnosis of advanced stage atrophic gastritis, and, importantly when H. pylori serology is also negative, endoscopy is recommended by the MAPS II Guideline Update 2019.
* Observational study (screening tests in 28 Japanese patients with confirmed histological AIG)
: 78.6% positive predictive value / (1) Serum gastrin >172pg/mL, (2) PgI: 14.5ng/dL, (3) PgI/II ratio: 2.1
* Non-invasive biomarkers를 이용한 AIG 환자의 prospective study 들이 적절한 long-term management를 결정하기 위해 서둘러 필요하겠습니다.
"AIG 환자에서는 내시경 감시를 고려해야 하며, 제한된 데이터 이자만, 3~5년 간격을 제안한다."
<Comment>
AIG-associated gastric cancer risk에 대한 과거 연구결과들은 preneoplastic gastric conditions (see section 2.1.4)인 pernicious anaemia를 포함 하고 있었으며, 이러한 연구들의 대부분은 H. pylori infection에 노출되었거나 가능성 있는 다수의 환자들이 포함되어 있었습니다. H.pylori의 과거 감염이나 현재 감염은 pangastritis atrophy를 유발하고, cancer promoting cofactor로써 작용하며, 결국 AIG-linked cancer risk로 언급하기에는 제한점이 있습니다 (figure 3).
최근 연구에 따르면, H. pylori infection과 동반되지 않은 AIG에서 gastric cancer risk를 평가할 때 정상 mucosecreting antrum (normal antral mucosa, only reactive gastropathy)이 필요하다는 내용은 위암 발생을 용이하게 하는 microenvironment에서 H. pylori의 영향을 배제하는데 타당할 것 같은 내용으로 보입니다. (Rugge M, Genta RM, Malfertheiner P, et al. Atrophic autoimmune gastritis: ’a muddled or misguided core concept compromises our overall comprehension of the problem’ Gut 2023;73:207–8.)
The risk of neuroendocrine neoplasia in AIG is related to the increase of serum gastrin (as a proxy for oxyntic atrophy) promoting ECL proliferation and potentially resulting in type I NETs (also referred to as gastric carcinoids). The optimal interval for AIG endoscopic surveillance has not been agreed upon. One small prospective study concluded that four yearly intervals were safe and sufficient to detect early neoplastic mucosal lesions (Lahner E, Caruana P, D’Ambra G, et al. First endoscopic-histologic follow-up in patients with body-predominant atrophic gastritis: when should it be done. Gastrointest Endosc 2001;53:443–8.).
Based on the available data on the negligible risk of gastric malignancies associated with primary AIG, an interval of 3–5years endoscopy and biopsy follow-up is suggested, more tailored for the early detection of NETs rather than for gastric cancer secondary prevention. (위 내시경의 주기는 gastric cancer 2차 예방 보다는 NETs의 조기 발견에 촛점을 두어 결정하는 것이 합당할 것으로 보여 집니다.)