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Article(id=1207433497170518274, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1207433493215289544, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2022.08.0817, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1631721600000, receivedDateStr=2021-09-16, revisedDate=null, revisedDateStr=null, acceptedDate=1644422400000, acceptedDateStr=2022-02-10, onlineDate=1765804178755, onlineDateStr=2025-12-15, pubDate=1661616000000, pubDateStr=2022-08-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1765804178755, onlineIssueDateStr=2025-12-15, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1765804178755, creator=13701087609, updateTime=1765804178755, updator=13701087609, issue=Issue{id=1207433493215289544, tenantId=1146029695717560320, journalId=1189873630562394117, year='2022', volume='47', issue='8', pageStart='745', pageEnd='850', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1765804177811, creator=13701087609, updateTime=1765804292764, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1207433975413444883, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1207433493215289544, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1207433975413444884, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1207433493215289544, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=817, endPage=823, ext={EN=ArticleExt(id=1207433498055516465, articleId=1207433497170518274, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Gastric ulcer associated with cytomegalovirus infection in immunocompetent patient: a case report and literature review, columnId=1190310109000602400, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Clinical Research, runingTitle=null, highlight=null, articleAbstract=

Objective To report a case of gastric ulcer associated with cytomegalovirus (CMV) infection in immunocompetent for improving the clinical recognition of the disease. Methods A 69-year-old patient with gastric ulcer caused by CMV infection was admitted to the 900th Hospital of the Joint Logistics Team on August 10, 2020. Biopsies were performed at the gastric ulcer and biopsy gastric mucosa samples were measured by hematoxylin-eosin (HE) staining and immunohistochemistry.The microscopic characteristics of the mucosal tissues, diagnosis and treatment experience of this case were analyzed and summarized. A literature review about CMV infection in gastric in inmmunocompetent patients was performed using PubMed search from database inception to July 2021. Results A total of 20 literatures were retrieved, involving 57 patients. A total of 58 patients were included in this article, including 39 males (67.2%) and 19 females (32.8%), with a ratio of men to women of 2.05:1. The average onset age of male was (52.4±16.0) years old, while (72.3±17.7) years old in female. The overwhelming majority of those patients were complicated with hypertension or type 2 diabetes mellitus. The most common symptoms were upper abdominal pain and gastrointestinal bleeding. The antrum of stomach was the most frequently affected site in gastric CMV disease, isolated gastric ulcer and multiple mucosal erosion were the main endoscopic appearance. CMV inclusion bodies were found either at the ulcer base or at the ulcer edges. There were 51.1% (24/47) of the patients treated with ganciclovir. However, 48.9% (23/47) of the patients were cured by symptomatic treatment. Conclusions On no consideration can clinically ignore CMV gastritis in adults without apparent immunosuppression when the symptoms as hematemesis, melena, and abdominal pain occur and antral gastric ulcer or multiple mucosal inflammation is seen endoscopically. Biopsies for CMV related tests, especially for pathological examination or histopathologic diagnosis are recommended. Antiviral therapy in people with clinical risk factors is essential for management of gastric CMV disease.

, correspAuthors=Yan-Fang Lin, authorNote=null, correspAuthorsNote=
*E-mail:
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目的 报告1例非免疫抑制患者感染巨细胞病毒(CMV)致胃溃疡的治疗过程并复习相关文献，以提升临床医师对该病的认识。方法 2020年8月10日解放军联勤保障部队第900医院消化内科收治1例69岁非免疫抑制CMV感染相关胃溃疡患者，采用HE染色及免疫组化法对活检胃黏膜标本进行检测，并对该病例的临床表现、内镜下特点、诊断及治疗情况等进行总结分析。检索美国国立医学图书馆(PubMed)数据库自建库至2021年7月报道的关于CMV感染致非免疫抑制患者胃部病变的文献，结合文献对该病的诊疗情况进行总结分析。结果 共检索到国外文献20篇，涉及57例CMV感染相关胃溃疡患者，结合该病例共纳入58例患者，其中男39例(67.2%)，女19例(32.8%)，男女比例为2.05:1；发病年龄男性(52.4±16.0)岁，女性(72.3±17.7)岁；合并高血压或2型糖尿病者居多。患者最常见的症状为上腹痛及上消化道出血，内镜下病灶好发于胃窦，以孤立性溃疡及多发糜烂为主，在溃疡基底或边缘活检HE染色均提示有包涵体。51.1%(24/47)的患者接受抗病毒治疗后痊愈，48.9%(23/47)的患者仅用对症支持治疗即痊愈。结论 临床医师需提高对CMV感染致非免疫抑制患者胃部病变的认识，当患者有呕血、黑便、上腹痛等症状且内镜下可见胃窦溃疡或多发黏膜糜烂时，需考虑CMV相关胃部病变，建议多块活检并行CMV相关检查尤其是病理学检查，确诊后建议对有高危因素者及时启动抗病毒治疗。

, correspAuthors=林燕芳, authorNote=null, correspAuthorsNote=
林燕芳，E-mail：
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王宝珊，硕士研究生，主要从事胃食管反流病发病机制方面的研究

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王宝珊，硕士研究生，主要从事胃食管反流病发病机制方面的研究

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王宝珊，硕士研究生，主要从事胃食管反流病发病机制方面的研究

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A. 入院时胃镜表现；B. 入院时上腹部CT平扫示胃壁弥漫性增厚；C. 入院时胃窦溃疡活检可见包涵体(×100)；D. 入院时胃窦免疫组化检测显示CMV抗体阳性(×100)；E. 治疗3周后胃镜表现；F. 治疗3周后胃窦活检未见包涵体(×40)；G. 治疗3周后胃窦免疫组化检测显示CMV抗体阴性(×40)；H. 治疗3周后复查上腹部CT显示胃壁增厚较前减轻；I. 治疗12周后胃镜表现

, figureFileSmall=tvlqldUR0cm5t7apNFX/4w==, figureFileBig=2TYlW5PBsD44g85E00LU4g==, tableContent=null), ArticleFig(id=1207433503596192330, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1207433497170518274, language=EN, label=Tab. 1, caption=

Laboratory findings of a non immunosuppressive patient with gastric ulcer caused by CMV infection

, figureFileSmall=null, figureFileBig=null, tableContent=
指标入院时抗病毒治疗3周后
血常规检查
 RBC(×1012/L)2.363.22
 Hb(g/L)6694
生化检查
 血糖(mmol/L)10.26.0
 HbA1c0.0810.056
 白蛋白(g/L)29.132.0
 尿蛋白(+++)(+)
 24 h尿蛋白定量(g/24 h)5.220.74
 血浆D-二聚体(mg/L)1.81.47
 CRP(mg/L)56.010.1
粪隐血(++)(–)
病毒检查
 CMV IgM(–)(–)
 CMV IgG(+)(+)
 CMV DNA(–)(–)
 HIVAb(–)(–)
 HCVAb(–)(–)
 HBsAg(–)(–)
), ArticleFig(id=1207433503730410064, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1207433497170518274, language=CN, label=表1, caption=

本例非免疫抑制患者感染巨细胞病毒致胃溃疡实验室指标变化

, figureFileSmall=null, figureFileBig=null, tableContent=
指标入院时抗病毒治疗3周后
血常规检查
 RBC(×1012/L)2.363.22
 Hb(g/L)6694
生化检查
 血糖(mmol/L)10.26.0
 HbA1c0.0810.056
 白蛋白(g/L)29.132.0
 尿蛋白(+++)(+)
 24 h尿蛋白定量(g/24 h)5.220.74
 血浆D-二聚体(mg/L)1.81.47
 CRP(mg/L)56.010.1
粪隐血(++)(–)
病毒检查
 CMV IgM(–)(–)
 CMV IgG(+)(+)
 CMV DNA(–)(–)
 HIVAb(–)(–)
 HCVAb(–)(–)
 HBsAg(–)(–)
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非免疫抑制患者感染巨细胞病毒致胃溃疡1例并文献复习
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王宝珊 , 陈志平 , 洪东贵 , 张观坡 , 柳刚 , 姚荔嘉 , 林燕芳 *
解放军医学杂志 | 临床研究 2022,47(8): 817-823
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解放军医学杂志 | 临床研究 2022, 47(8): 817-823
非免疫抑制患者感染巨细胞病毒致胃溃疡1例并文献复习
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王宝珊, 陈志平, 洪东贵, 张观坡, 柳刚, 姚荔嘉, 林燕芳*
作者信息
  • 解放军联勤保障部队第900医院消化内科，福建福州 350025

    • 王宝珊，硕士研究生，主要从事胃食管反流病发病机制方面的研究

通讯作者:

林燕芳，E-mail：
Gastric ulcer associated with cytomegalovirus infection in immunocompetent patient: a case report and literature review
Bao-Shan Wang, Zhi-Ping Chen, Dong-Gui Hong, Guan-Po Zhang, Gang Liu, Li-Jia Yao, Yan-Fang Lin*
Affiliations
  • Department of Gastroenterology, the 900th Hospital of the Joint Logistics Support Forces of Chinese PLA, Fuzhou, Fujian 350025,China
出版时间: 2022-08-28 doi: 10.11855/j.issn.0577-7402.2022.08.0817
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摘要
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目的 报告1例非免疫抑制患者感染巨细胞病毒(CMV)致胃溃疡的治疗过程并复习相关文献，以提升临床医师对该病的认识。方法 2020年8月10日解放军联勤保障部队第900医院消化内科收治1例69岁非免疫抑制CMV感染相关胃溃疡患者，采用HE染色及免疫组化法对活检胃黏膜标本进行检测，并对该病例的临床表现、内镜下特点、诊断及治疗情况等进行总结分析。检索美国国立医学图书馆(PubMed)数据库自建库至2021年7月报道的关于CMV感染致非免疫抑制患者胃部病变的文献，结合文献对该病的诊疗情况进行总结分析。结果 共检索到国外文献20篇，涉及57例CMV感染相关胃溃疡患者，结合该病例共纳入58例患者，其中男39例(67.2%)，女19例(32.8%)，男女比例为2.05:1；发病年龄男性(52.4±16.0)岁，女性(72.3±17.7)岁；合并高血压或2型糖尿病者居多。患者最常见的症状为上腹痛及上消化道出血，内镜下病灶好发于胃窦，以孤立性溃疡及多发糜烂为主，在溃疡基底或边缘活检HE染色均提示有包涵体。51.1%(24/47)的患者接受抗病毒治疗后痊愈，48.9%(23/47)的患者仅用对症支持治疗即痊愈。结论 临床医师需提高对CMV感染致非免疫抑制患者胃部病变的认识，当患者有呕血、黑便、上腹痛等症状且内镜下可见胃窦溃疡或多发黏膜糜烂时，需考虑CMV相关胃部病变，建议多块活检并行CMV相关检查尤其是病理学检查，确诊后建议对有高危因素者及时启动抗病毒治疗。

非免疫抑制患者  /  巨细胞病毒  /  胃溃疡  /  文献复习

Objective To report a case of gastric ulcer associated with cytomegalovirus (CMV) infection in immunocompetent for improving the clinical recognition of the disease. Methods A 69-year-old patient with gastric ulcer caused by CMV infection was admitted to the 900th Hospital of the Joint Logistics Team on August 10, 2020. Biopsies were performed at the gastric ulcer and biopsy gastric mucosa samples were measured by hematoxylin-eosin (HE) staining and immunohistochemistry.The microscopic characteristics of the mucosal tissues, diagnosis and treatment experience of this case were analyzed and summarized. A literature review about CMV infection in gastric in inmmunocompetent patients was performed using PubMed search from database inception to July 2021. Results A total of 20 literatures were retrieved, involving 57 patients. A total of 58 patients were included in this article, including 39 males (67.2%) and 19 females (32.8%), with a ratio of men to women of 2.05:1. The average onset age of male was (52.4±16.0) years old, while (72.3±17.7) years old in female. The overwhelming majority of those patients were complicated with hypertension or type 2 diabetes mellitus. The most common symptoms were upper abdominal pain and gastrointestinal bleeding. The antrum of stomach was the most frequently affected site in gastric CMV disease, isolated gastric ulcer and multiple mucosal erosion were the main endoscopic appearance. CMV inclusion bodies were found either at the ulcer base or at the ulcer edges. There were 51.1% (24/47) of the patients treated with ganciclovir. However, 48.9% (23/47) of the patients were cured by symptomatic treatment. Conclusions On no consideration can clinically ignore CMV gastritis in adults without apparent immunosuppression when the symptoms as hematemesis, melena, and abdominal pain occur and antral gastric ulcer or multiple mucosal inflammation is seen endoscopically. Biopsies for CMV related tests, especially for pathological examination or histopathologic diagnosis are recommended. Antiviral therapy in people with clinical risk factors is essential for management of gastric CMV disease.

immunocompetent patients  /  cytomegalovirus  /  stomach ulcer  /  literature review
王宝珊, 陈志平, 洪东贵, 张观坡, 柳刚, 姚荔嘉, 林燕芳. 非免疫抑制患者感染巨细胞病毒致胃溃疡1例并文献复习. 解放军医学杂志, 2022 , 47 (8) : 817 -823 . DOI: 10.11855/j.issn.0577-7402.2022.08.0817
Bao-Shan Wang, Zhi-Ping Chen, Dong-Gui Hong, Guan-Po Zhang, Gang Liu, Li-Jia Yao, Yan-Fang Lin. Gastric ulcer associated with cytomegalovirus infection in immunocompetent patient: a case report and literature review[J]. Medical Journal of Chinese People’s Liberation Army, 2022 , 47 (8) : 817 -823 . DOI: 10.11855/j.issn.0577-7402.2022.08.0817
正文
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巨细胞病毒(cytomegalovirus，CMV)导致的胃肠道感染通常见于免疫功能缺陷患者，如获得性免疫缺陷综合征、恶性肿瘤患者及接受器官移植、长期服用免疫抑制剂等，是免疫抑制患者死亡的主要原因之一[1]。近年来，针对非免疫抑制患者感染CMV致胃部病变的报道逐渐增多，有研究显示CMV感染的发病率约为0.3%[2]，然而国内尚未报道有明确病理学证据的非免疫抑制患者CMV相关胃部病变。本文报告1例非免疫抑制患者感染CMV致胃溃疡病例，同时回顾性分析文献报道的非免疫抑制患者CMV相关胃部病变的资料，总结其临床表现、内镜下特点、诊断及治疗，旨在提高临床对该病的认识，降低漏诊率。
1 病例资料
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患者，男，69岁，因“反复上腹胀伴食欲缺乏20 d”于2020年8月10日入院。患者入院前20 d无明显诱因出现上腹胀，进食后明显，伴食欲缺乏、消瘦，进食量减为原来的1/3~1/2，20 d体重减轻3 kg。无恶心、呕吐，无腹痛、腹泻，无发热、畏冷，无反酸、烧心，无吞咽困难，无黄疸，无咳嗽、咳痰。门诊胃镜检查结果如图1A所示，胃窦大弯处见一约40 mm×50 mm巨大黏膜凹陷，延续至胃窦后壁，周边黏膜呈堤状隆起，溃疡底部凹凸不平，上披污苔。取溃疡底部组织活检2块，溃疡边缘组织活检4块，镜下诊断为“胃窦巨大溃疡(性质待定)”，遂收入院。患者既往有2型糖尿病史20年，使用“甘精胰岛素8 U，1次/d睡前+门冬胰岛素6 U，3次/d餐前”降糖，近期监测空腹血糖于8~9 mmol/L范围波动。患者有高血压病史20年，平素使用“厄贝沙坦150 mg，1次/d+苯磺酸氨氯地平5 mg，1次/d早晨”降压，血压控制稳定。患者对造影剂过敏，表现为增强造影剂注入血管后出现面部及上胸部瘙痒伴风团，余无特殊；个人史、婚育史、家族史均无特殊。
1.1 入院查体
体温36.5 ℃，脉搏88次/min，呼吸18次/min，血压143/88 mmHg (1 mmHg≈0.133 kPa)。营养中等，贫血貌，意识清醒，全身皮肤黏膜稍苍白，无皮疹、皮下出血，全身浅表淋巴结未触及肿大。结膜苍白，巩膜无黄染，口唇稍苍白，心脏及肺部查体未见异常。腹平坦，腹部柔软，上腹部压痛，无反跳痛，余腹部未见压痛及反跳痛，肝脾未触及，Murphy征阴性。肠鸣音正常，4次/min，双下肢轻度凹陷性水肿。
1.2 辅助检查
血常规、大便隐血试验、尿常规、生化指标结果见表1。C-反应蛋白(C-reactive protein，CRP)56 mg/L(正常<7.2 mg/L)，尿微量白蛋白/肌酐3600.89 mg/g，D-二聚体1.8 mg/L(正常<0.5 mg/L)，糖化血红蛋白(hemoglobin A1c，HbA1c)0.081，血清铁5.0 μmol/L(正常11~28 μmol/L)，总铁结合力20.4 μmol/L(正常50~77 μmol/L)，CMV免疫球蛋白G(immunoglobulin G，IgG)阳性，CMV免疫球蛋白M(immunoglobulin M，IgM)、EB病毒(Epstein-Barr virus，EBV) IgM、EBV IgG、EBV免疫球蛋白A(immunoglobulin A，IgA)、EBV DNA、CMV DNA均为阴性，凝血4项、乙肝两对半、丙型肝炎病毒抗体(hepatitis C virus antibody，HCVAb)、人类免疫缺陷病毒抗体(human immunodeficiency virus antibody，HIVAb)、梅毒抗体、癌胚抗原(carcinoembryonic antigen，CEA)、甲胎蛋白(α-fetoprotein，AFP)、糖类抗原19-9(glucoprotein antigen19-9，CA19-9)、前列腺特异性抗原(prostate specific antigen，PSA)、自身免疫全套检测、铁蛋白、叶酸、维生素B12、降钙素原(procalcitonin，PCT)均未见异常。胸部+全腹部CT平扫显示胃壁弥漫性增厚(图1B)，胃镜活检病理显示局灶血管内皮细胞可见包涵体(图1C)，免疫组化检测(ZM-0098 CMV抗体试剂，北京中杉金桥生物技术有限公司)显示抗CMV抗体阳性(图1D)；髂骨上棘穿刺活检病理显示三系造血细胞存在，免疫组化未见前体细胞增生及异常定位，轻链无失衡，无肿瘤性病变。
1.3 治疗及转归
患者入院后于2020年8月10日－9月11日给予雷贝拉唑20 mg，2次/d静脉滴注，铝镁加混悬液15 ml，3次/d口服，康复新液10 ml，3次/d口服，枸橼酸莫沙必利片5 mg，3次/d口服，腹胀、食欲缺乏较入院时稍缓解，但进食量仍为原来的1/2。按上述方案治疗期间体重仍进行性减轻2 kg。于2020年9月13日起，在上述用药方案的基础上加用更昔洛韦(325 mg/次，2次/d)静脉滴注，持续3周，期间监测肝肾功能均正常，3周后患者腹胀、食欲缺乏症状较前明显缓解，未继续消瘦。复查血常规、大便隐血试验、尿常规、生化指标较前均好转，CRP 10.1 mg/L，D-二聚体1.47 mg/L，HbA1c 0.056，CMV IgG阳性，CMV IgM阴性(表1)。复查胃镜显示胃窦溃疡较前明显缩小(约10 mm×18 mm，图1E)，病理检查未见包涵体(图1F)，免疫组化检测显示抗CMV抗体阴性(图1G)。全腹部CT平扫显示胃壁增厚较前减轻(图1H)。考虑治疗有效，继续使用更昔洛韦(剂量及使用频次同前)9周(即总疗程12周)，同时口服雷贝拉唑钠肠溶片(波利特)20 mg，1次/d，铝镁加混悬液15 ml，3次/d治疗。于2020年12月于本院门诊随诊，自诉体重保持稳定，未继续下降，已无腹胀、食欲缺乏，进食量恢复正常，复查胃镜提示胃窦溃疡已完全愈合(图1I)。建议3个月后返院再次复查胃镜及全面检查，患者因个人原因拒绝。
2 文献复习
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2.1 文献检索
2.1.1 入选及排除标准
(1)年龄≥18岁；(2)内镜下病理和(或)免疫组化证实为CMV相关胃部病变，HE染色可见包涵体，免疫组化检测CMV抗体阳性；(3)非免疫抑制患者，定义为除外免疫抑制状态[获得性免疫缺陷综合征、恶性肿瘤、实体器官移植、骨髓移植、6个月内使用过化疗药物、长期使用免疫抑制剂(静脉给药或口服泼尼松龙或等剂量其他糖皮质类激素≥20 mg/d，使用时间>2周)]的患者[3]。排除非英语文献。
2.1.2 检索方法
以“巨细胞病毒”“胃”为检索词，检索万方数据、中国知网、维普数据库自建库至2021年7月报道的有关CMV相关胃部病变的文献。以“Cytomegalovirus Infections”“Salivary Gland Virus Disease”“Infections，Cytomegalovirus”“Cyto-megalovirus Infection”“Infection，Cytomegalovirus”“Cytomegalic Inclusion Disease”“Cytomegalic Inclusion Diseases”“Disease，Cytomegalic Inclusion”“Diseases，Cytomegalic Inclusion”“Inclusion Disease，Cytomegalic”“Inclusion Diseases，Cytomegalic”“Inclusion Disease”“Inclusion Diseases”“Immunocompetence”“Immun-ological Competence”“Competence，Immunological”“Competence，Immunologic”“Immunologic Competence”“Gastritis”“Gastritides”为检索词，检索美国国立医学图书馆(PubMed)数据库自建库至2021年7月报道的有关非免疫抑制患者CMV相关胃部病变的文献。共检索到国外文献20篇57例[1, 3-21]，结合本文报告的病例，共纳入58例进行分析。未检索到国内相关文献。
2.2 临床特点分析
2.2.1 一般临床资料
58例患者中，男39例(占67.2%)，女19例(占32.8%)，男女比例为2.05:1。20例未在文献中说明年龄，其余38例发病年龄为(58.6±18.8)岁，其中男性发病年龄(52.4±16.0)岁，女性(72.3±17.7)岁。58例中合并肝硬化3例(5.2%)，2型糖尿病9例(15.5%)，冠心病3例(5.2%)，高血压7例(12.1%)，1例(1.7%)长期口服非甾体抗炎药。
2.2.2 临床症状
58例患者中，有15例未详述具体临床症状，其余43例中，上腹痛19例(44.2%)，上消化道出血(呕血、黑便)13例(30.2%)，发热9例(20.9%)，腹胀、食欲缺乏7例(16.3%)，呕吐5例(11.6%)，乏力2例(4.7%)，消化道穿孔1例(2.3%)，无症状1例(2.3%)。
2.2.3 内镜下表现
病灶位置位于胃窦39例(67.2%)，胃体16例(27.6%)，胃角11例(19.0%)，贲门5例(8.6%)，胃底3例(5.2%)。内镜下较多见的病灶形态为孤立性溃疡(26例，44.8%)及多发糜烂(21例，36.2%)，其余包括多发溃疡14例(24.1%)，息肉样隆起6例(10.3%)，结节样增生3例(5.2%)，孤立隆起糜烂4例(6.9%)。
2.2.4 活检部位
40例内镜下表现为溃疡，有4例活检溃疡基底，7例活检溃疡边缘，29例未详述，活检组织行HE染色均可见包涵体。
2.2.5 其他检查
20例未行CMV血清学检测。余38例患者中，CMV IgM阳性11例(28.9%)，CMV IgG阳性9例(23.7%)。
2.2.6 治疗及疗程
11例未详述治疗方法。余47例患者中，给予抗病毒治疗24例(51.1%)，使用更昔洛韦5 mg/kg静脉滴注2次/d，疗程1~16周；对症支持治疗23例(48.9%)。
2.2.7 转归
3例患者失访，1例因消化道穿孔行胃大部切除术，余54例(93.1%)均治愈。
3 讨论
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近年来，关于轻度免疫功能异常[非免疫抑制，如高龄(年龄>55岁)、2型糖尿病、肾衰竭、妊娠、心力衰竭(心衰)等]的宿主合并CMV感染的个案报道逐渐增多[22-26]。CMV感染的发病率约为0.3%，且病死率随患者年龄增大而逐渐升高[2]。因此，即使对轻度免疫功能异常的患者，也需将CMV作为一个潜在的致病因素考虑。
本文回顾分析了58例非免疫抑制患者感染CMV致胃部病变患者的资料，结果显示该病患者以中老年男性为主，男性平均发病年龄明显低于女性，且合并高血压、2型糖尿病者居多。最常见的临床表现为上腹痛、上消化道出血(如呕血、黑便)，其次为发热及腹胀、食欲缺乏。内镜下病变部位多见于胃窦，镜下表现多样，缺乏特异性，以孤立性溃疡及多发糜烂为主，其中，孤立性溃疡常被误诊为恶性肿瘤。本例患者高龄，主要以腹胀、食欲缺乏发病，同时合并消化道出血表现(大便隐血阳性)，内镜下表现为胃窦孤立的巨大溃疡，故当轻度免疫功能异常宿主具有上述临床症状及内镜下表现时，临床医师需考虑CMV感染的可能。
非免疫抑制患者胃部病变合并CMV感染的临床表现无明显特异性，内镜下表现亦缺乏特异性，从孤立性隆起糜烂、结节样增生、息肉样隆起到多发溃疡、孤立溃疡、多发糜烂均可见，内镜下表现与胃部疾病(如胃息肉、胃良性溃疡、胃恶性溃疡、糜烂性胃炎等)难以通过肉眼直接鉴别。此外，有患者经过3次胃黏膜病理活检方证实CMV感染[13]，可见该病极易误诊、漏诊。因此当非免疫抑制宿主经对症治疗后其临床症状及内镜下表现仍未见好转时，需考虑合并CMV感染的可能，建议多次重复活检或深挖活检以减少误诊及漏诊。
CMV相关胃部病变诊断的关键在于活检组织中发现包涵体和(或)免疫组化检测显示CMV抗体阳性。有研究表明，溃疡基底的病毒载量较溃疡边缘更高[13]，但本研究通过回顾有详细资料记录的11例合并溃疡表现的CMV相关胃部病变患者，发现不论在溃疡基底还是溃疡边缘进行活检，HE染色均提示有包涵体，本例患者同时活检溃疡基底及边缘，亦均检出CMV包涵体，故病毒载量于溃疡何处更高尚无定论。2013年美国消化内镜学会(American Society for Gastrointestinal Endoscopy，ASGE)共识推荐对临床表现或内镜下怀疑恶性胃溃疡的患者，溃疡边缘及基底均需活检[27]，因此，对于镜下表现为胃溃疡的病例，若无禁忌证可同时活检溃疡基底及边缘，以提高诊断准确率。焉鹏等[28]采用聚合酶链反应(PCR)检测了138例胃炎患者胃黏膜组织中的人巨细胞病毒DNA(HCMV-DNA)含量，同时平行测定上述患者的血清HCMV-IgG，发现难治性胃炎组患者胃黏膜HCMV-DNA阳性率明显高于普通胃炎组，而两组患者的血清HCMV-IgG水平比较差异无统计学意义，表明PCR在诊断CMV感染致胃部病变中具有一定价值，临床上可通过活检和(或)PCR提高诊断率，避免漏诊。既往血清学检测是辅助诊断CMV感染的重要方法[19]，然而在本文38例行CMV血清学检测的患者中，CMV IgM阳性病例仅占28.9%，故CMV血清学检测在诊断CMV感染致胃部病变方面的优势不足。
CMV诱发器官感染的机制为CMV在骨髓CD34+/CD33+髓系祖细胞及外周血CD14+单核细胞中潜伏感染，当机体受到细胞因子[如肿瘤坏死因子-α(tumor necrosis factor-α，TNF-α)、γ干扰素(interferon-γ，IFN-γ)等]的刺激后，被CMV潜伏感染的细胞进入组织，分化为巨噬细胞或树突状细胞，释放CMV，造成CMV的再激活[29-31]。免疫力正常宿主可分泌抗CMV抗体及CMV特异性CD8+ T细胞，阻止CMV被进一步激活。然而，糖尿病患者的高血糖状态可增加TNF-α表达、减少CD4+ T细胞及CD8+ T细胞数量，造成不同程度的免疫抑制，使CMV更易激活[32-33]。此外，有报道在肾移植患者中，CMV特异性抗体的减少及低蛋白血症可促使CMV再激活[34]。基于以上研究，本例HbA1c、空腹血糖均提示近期血糖控制不佳，生化指标提示低蛋白血症，可能是CMV再激活的诱因。故临床医师需提高警惕，加深对非免疫抑制患者感染CMV的认识，尤其是合并糖尿病和(或)营养状态差的高龄患者。
CMV在胃肠道中主要感染基质细胞及血管内皮细胞，被感染的血管内皮细胞可释放血管性血友病(von Willebrand，vW)因子，促进血小板黏附聚集，导致局部组织器官血栓形成，严重者可致多器官衰竭[35-36]。因此，CMV相关胃部病变主要表现为溃疡或多发糜烂的机制可能是CMV感染血管内皮细胞，诱导局部血栓形成，造成胃黏膜组织缺血缺氧。
有文献报道，CMV感染可能通过直接抑制骨髓造血祖细胞的分化造成基质细胞功能障碍，从而诱发溶血性贫血、骨髓增生异常综合征、全血细胞减少等[37-38]。因此，当临床确诊CMV感染且合并贫血时，可进一步完善骨髓穿刺活检以排除CMV相关贫血。对本例行骨髓穿刺活检未见骨髓抑制，考虑为上消化道出血所致贫血。
目前关于非免疫抑制患者感染CMV致胃部病变的治疗方法颇有争议。有研究表明，抗病毒治疗可快速缓解高龄及重症患者的临床症状[39-40]。本文有翔实资料的47例CMV感染患者中，51.1%接受了抗病毒治疗后痊愈。值得注意的是，有48.9%的患者仅给予对症支持治疗，亦得到治愈。因此，是否启动抗病毒治疗需综合评估患者的免疫状态，当合并高龄、糖尿病、肾衰竭、心衰、低蛋白血症等高危因素时，抗病毒治疗不失为一种有效的手段。
综上所述，目前CMV感染致胃溃疡的报道尚少，临床医师需提高对该病的认识。当非免疫抑制宿主有呕血、黑便、上腹痛、发热等症状且内镜下可见胃窦溃疡或多发黏膜糜烂时，需考虑CMV相关胃部病变的可能，建议进行病灶边缘及病灶基底多块活检，并行CMV相关检测，尤其是病理学检查，必要时深挖活检或多次重复活检。确诊后根据患者有无高龄、糖尿病、肾衰竭、心衰、低蛋白血症等高危因素决定是否启动抗病毒治疗。
基金
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  • 福建省自然科学基金面上项目(2020J011140)
  • 联勤保障部队第900医院院立课题(2019L04)
文献
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参考文献 引证文献
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2022年第47卷第8期
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doi: 10.11855/j.issn.0577-7402.2022.08.0817
  • 接收时间：2021-09-16
  • 首发时间：2025-12-15
  • 出版时间：2022-08-28
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  • 收稿日期：2021-09-16
  • 录用日期：2022-02-10
基金
Natural Science Foundation of Fujian Province(2020J011140)
福建省自然科学基金面上项目(2020J011140)
Project of the 900th Hospital of the Joint Logistics Team(2019L04)
联勤保障部队第900医院院立课题(2019L04)
作者信息
    解放军联勤保障部队第900医院消化内科，福建福州 350025

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2种不同金属材料的力学参数
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Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
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species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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