Rugge Massimo, Bricca Ludovica, Guzzinati Stefano, Sacchi Diana, Pizzi Marco, Savarino Edoardo, Farinati Fabio, Zorzi Manuel, Fassan Matteo, Dei Tos Angelo Paolo, Malfertheiner Peter, Genta Robert M, Graham David Y
Department of Medicine - DIMED, Ringgold ID 9308, Padova, Veneto, Italy
Veneto Tumor Registry, Azienda Zero, Padova, Veneto, Italy.
Gut. 2023 Jan;72(1):30-38. doi: 10.1136/gutjnl-2022-327827. Epub 2022 Jun 30.
Autoimmune gastritis (AIG) is an immunomediated disease targeting parietal cells, eventually resulting in oxyntic-restricted atrophy. This long-term follow-up study aimed at elucidating the natural history, histological phenotype(s), and associated cancer risk of patients with AIG consistently tested -negative (naïve -negative subjects).
Two-hundred eleven naïve -negative patients (tested by serology, histology, molecular biology) with AIG (F:M=3.15:1; p<0.001) were prospectively followed up with paired biopsies (T1 vs T2; mean follow-up years:7.5 (SD:4.4); median:7). Histology distinguished non-atrophic versus atrophic AIG. Atrophy was further subtyped/scored as non-metaplastic versus metaplastic (pseudopyloric (PPM) and intestinal (IM)). Enterochromaffin-like-cell (ECL) status was categorised as diffuse versus adenomatoid hyperplasia/dysplasia, and type 1 neuroendocrine tumours (Type1-NETs).
Over the long-term histological follow-up, AIG consistently featured oxyntic-predominant-mononuclear inflammation. At T1, PPM-score was greater than IM (200/211 vs 160/211, respectively); IM scores increased from T1 to T2 (160/211 to 179/211), with no changes in the PPM prevalence (T1=200/211; T2=201/211). At both T1/T2, the prevalence of OLGA-III-stage was <5%; no Operative Link on Gastritis Assessment (OLGA)-IV-stage occurred. ECL-cell-status progressed from diffuse to adenomatoid hyperplasia/dysplasia (T1=167/14 vs T2=151/25). Type1-NETs (T1=10; T2=11) always coexisted with extensive oxyntic-atrophy, and ECL adenomatoid-hyperplasia/dysplasia. No excess risk of gastric or other malignancies was found over a cumulative follow-up time of 10 541 person years, except for (marginally significant) thyroid cancer (SIR=3.09; 95% CI 1.001 to 7.20).
Oxyntic-restricted inflammation, PPM (more than IM), and ECL-cell hyperplasia/neoplasia are the histological AIG hallmarks. Compared with the general population, corpus-restricted inflammation/atrophy does not increase the GC risk. The excess of GC risk reported in patients with AIG could plausibly result from unrecognised previous/current comorbidity.
自身免疫性胃炎（AIG）是一种针对壁细胞的免疫介导性疾病，最终导致胃体局限性萎缩。这项长期随访研究旨在阐明持续检测为阴性（初始阴性受试者）的AIG患者的自然病史、组织学表型及相关癌症风险。
对211例初始阴性的AIG患者（通过血清学、组织学、分子生物学检测；女性与男性比例为3.15:1；p<0.001）进行前瞻性随访，并进行配对活检（T1与T2；平均随访年限：7.5（标准差：4.4）；中位数：7）。组织学区分非萎缩性与萎缩性AIG。萎缩进一步分为非化生型与化生型（假幽门化生（PPM）和肠化生（IM））并进行评分。嗜铬样细胞（ECL）状态分为弥漫性增生与腺瘤样增生/发育异常，以及1型神经内分泌肿瘤（Type1-NETs）。
在长期组织学随访中，AIG始终以胃体为主的单核炎症为特征。在T1时，PPM评分高于IM（分别为200/211和160/211）；IM评分从T1到T2增加（从160/211到179/211），而PPM患病率无变化（T1 = 200/211；T2 = 201/211）。在T1/T2时，OLGA-III期患病率<5%；未出现胃炎评估手术链接（OLGA）-IV期。ECL细胞状态从弥漫性增生进展为腺瘤样增生/发育异常（T1 = 167/14 vs T2 = 151/25）。1型神经内分泌肿瘤（T1 = 10；T2 = 11）总是与广泛的胃体萎缩和ECL腺瘤样增生/发育异常共存。在累计随访10541人年的时间里，未发现胃癌或其他恶性肿瘤的额外风险增加，但甲状腺癌有（边缘显著）增加（标准化发病比=3.09；95%置信区间1.001至7.20）。
胃体局限性炎症、PPM（多于IM）和ECL细胞增生/肿瘤形成是AIG的组织学特征。与普通人群相比，胃体局限性炎症/萎缩不会增加胃癌风险。AIG患者报告的胃癌风险增加可能合理地归因于未被识别的既往/当前合并症。
