【摘要】目的用克拉霉素(CLA)与胶体次枸橼酸铋(CBS)联合应用，加另一种抗生素，治疗儿童Hp相关性胃炎，以评价不同治疗方案的疗效和观察根除Hp感染与胃炎好转的关系。方法276例4～14岁患儿经胃镜检查确诊为幽门螺杆菌(Hp)相关性胃十二指肠疾病，随机分为A、B、C、D四组，接受以CBS为主的三联疗法。A、C、D组用克拉霉素(CLA)15 mg/(kg·d)联合CBS 9 mg/(kg·d)，再加另一种抗生素，［A组羟氨苄青霉素(阿莫西林)(AMO)40 mg/(kg·d)，C组甲硝唑(Met)18 mg/(kg·d)，D组呋喃唑酮(FUR)4 mg/(kg·d)］，治疗1周。B组是标准三联疗法(CBS+AMO+Met，剂量同上)，治疗2周。服药前及停用抗Hp治疗后4周以上作胃镜检查及Hp检测，或停药4周以上做¹³碳(¹³C)尿素呼气试验。全部病例完成治疗和复查。结果(1)治疗后Hp根治率A组54％(21/39)，B组81％(47/58)，C组93％(42/45)，D组91％(122/134)。C、D二组根除率均高于B组根除率的10％以上。四个方案组对Hp根除率疗效差异有非常显著性，χ²=34.730，P＜0.01。(2)各组与标准方案B组比较，A方案较B方案差，C、D方案Hp根除率高于B方案，其中人数较多的D方案差异具有显著性(χ²=3.847，P＜0.05)。(3)A、C、D三组治疗后3d内、1周末和2周末的疼痛缓解率分别超过75 %、90 %、95 %以上。四组疼痛缓解率经log rank检验得χ²=19.23，P=0.002，差异有显著性。(4)四组Hp根除率高，疼痛缓解率高，尤其C、D二组，不仅Hp根除率高，胃炎症状缓解好，即便Hp未根除，胃炎症状也得到缓解。(5)四组副反应有轻度恶心、呕吐、腹泻和少量皮疹，其发生率A组最低5 %，其次C组7 %，再次D组8 %，B组9 %，均不影响治疗，停药后症状消失。结论 儿童Hp相关性胃十二指肠疾病经根除Hp的治疗，能使胃炎得到满意改善。以铋剂为主联合克拉霉素和呋喃唑酮或甲硝唑组成两组三联短程疗法治疗儿童Hp相关性胃十二指肠疾病，具有疗程短，疗效高，副作用小和Hp根除率高等优点。

Treatment of Helicobacter pylori-related gastritis in children with different regimens

KANG Hongzhuang, ZHA Jianzhong, LI Bingbing

（Department of Pediatrics, Ninth People′s Hospital, Shanghai Second Medical University, Shanghai 200011, China）

【Abstract】ObjectiveTo evaluate the therapeutic effect of different programs consisted of clarithromycin (CLA), colloidal bismuth subsitrate (CBS) plus another antibacterial agent by comparing to standard triple therapy on Helicobacter pylori (Hp)-related gastritis in children. MethodsTwo hundred and seventy-six children (4 to 14 years old) with gastroscopically confirmed Hp-related gastroduodenal disease were divided into 4 groups (A, B, C and D) at random. These children were given 4 different triple therapies with each of which contained CBS. Groups A, C and D were given CBS, 4.5 mg/kg bid; CLA 7.5 mg/kg bid as a second drug, plus another antibacterial agent, i.e., amoxicillin (AMO), 20 mg/kg bid for group A, metronidazole (Met), 9 mg/kg bid group C and: furazolidone (FUR), 2 mg/kg bid for group D, for one week. Group B was given a standard triple therapy (CBS+AMO+Met, the same dosage as mentioned above) for two weeks. Gastroscopy was performed in these patients prior to medication and over 4 weeks after therapy and Hp infection was detected by culture and histology or by ¹³C-urea breath test (¹³C-UBT) over 4 weeks after the therapy. All the patients completed the whole study.Results(1) The eradication rates of Hp were as follows: group A: 54 % (21/39); group B: 81 % (47/58); group C: 93 % (42/45) and group D: 91 % (122/134). The eradication rates of group C and D were about 10 % higher than group B. The differences were highly significant (χ²=34.730, P＜0.001). (2) The comparison among the 4 groups showed that group A had poorest effect, while group D had the highest eradicationrate (χ²=3.847, P＜0.05). (3) Within 3 days, 1 and 2 weeks after therapy, the pain relief rates in groups A, C, and D were 75 %, 90 % and 95 %, respectively. (4) The side effects in the 4 groups (nausea, vomiting, diarrhea and a few rashes) were mild. Their occurrence rate was the lowest in group A (5 %) followed by group C (7 %) and group D (8 %); the highest (9 %) was seen in group B. The symptoms caused by the side effects disappeared when the medication was completed. ConclusionSatisfactory effect was achieved in treatment of Hp-related gastrodudenal disease after the eradication of Hp in the children studied. Low dose triple therapy with CBS, CLA and Met or FUR for a week was highly effective and well tolerated in treatment of Hp-related gastritis in children. The side effects were minor. The symptoms of gastritis were well relieved. Therefore, the triple therapy composed of CBS, CLA and Met seemed to be of great value and worthy of clinical application.

【Key words】Helicobacter pylori; Gastritis; Child; Duodenal; Bismuth; Clarithromycin

幽门螺杆菌(Helicobacter pylori，简称Hp)与慢性胃炎、消化性溃疡密切相关，根治Hp感染胃粘膜组织的炎症明显改善和明显降低消化性溃疡的复发率。最近报道在人的一生中儿童期较成人期容易获得Hp感染，儿童中Hp感染率不仅很高，且随年龄增加而递增^［1-3］。故研究儿童人群Hp的感染，Hp与儿童胃十二指肠疾病的关系；探讨一个根除率高，安全性大，复发率低，服药时间短的有效小儿Hp根治方案，是目前迫切需要解决的问题。本研究应用克拉霉素(CLA)、联合应用胶体次枸橼酸铋(CBS)，加另一种抗生素，与标准三联疗法对照，治疗儿童Hp相关性胃炎，以评价不同治疗方案的疗效，和观察根除Hp感染与胃炎好转的关系。现报道如下。

材料和方法

一、研究对象

1．受试儿童:均为因反复腹痛、恶心、呕吐、腹胀、嗳气、纳差等上消化道症状而来我院就诊的患儿，共276例，男122例，女154例。最小年龄4岁，最大年龄14岁，平均8.5岁。病程最短1个月，最长8年。

2．入选标准：凡确诊为慢性胃炎，且Hp呈阳性，在1个月内未接受过抗Hp治疗，无严重脏器功能障碍者被纳入本研究范围。治疗前做电子胃镜检查，并取胃窦粘膜活检组织作快速尿素酶试验，Hp培养和组织病理学检查。

3.Hp阳性判断标准：（1)胃粘膜Hp培养呈阳性。(2)组织病理学检测Hp呈阳性。(3)两者均呈阳性。

二、治疗方案

将符合入选标准的276例患儿，由预先设计好的随机表按入组先后决定治疗方案。原设计时为A、B、C、D 4个组别，各组50例。后经治疗得知D组疗效较好，C组有轻微不良反应，故200例之后的病例较多地分入D组。随机表的安排未考虑性别、年龄和病程等因素。A、C、D组方案用CBS 9 mg/(kg^．d)和CLA 15 mg/(kg^．d)，再加另一抗生素，［A组用羟氨苄青霉素(阿莫西林)(AM0) 40 mg/(kg^．d)，C组用甲硝唑(Met) 18 mg/(kg^．d)，D组用呋喃唑酮(FUR) 4 mg/(kg^．d)］，每日二次口服，疗程7 d。B组为标准三联疗法(CBS、AMO和Met剂量方法同上)，疗程14 d。治疗期间不加服其他药物，治疗结束至Hp复查前也不用任何药物(包括抗生素、铋剂、质子泵抑制剂和胃粘膜保护剂等)。

三、观察疗效和副反应

各组病例治疗期间详细记录治疗前后上腹痛等症状消失时间及治疗期间副反应症状和程度。

四、Hp复查

入选的276例于疗程结束后至少4周以上，复查胃镜并检测Hp或做¹³碳 (¹³C)尿素呼气试验(¹³C-UBT)，以判断Hp是否已被根除。

五、统计学处理

不同方案治疗组Hp根除率用χ²检验，二组别比较用方差分析。四组缓解率的比较采用生存分析方法，对于每一病例资料列出其缓解天数，这是观察完全的数据。如果未缓解就列出尚未缓解的天数，这是结尾，数据为观察不完全的数据，然后使用生存分析中的乘积极限法(product-limit method)估计每个时间点的缓解率及其标准误。不同方案治疗组列出治疗后3 d、1周、2周的缓解率及其标准误。

结果

一、不同方案治疗组Hp根除率比较

从表1可见治疗后Hp根除率A组54 %(21/39)，B组81 %(47/58)，C组93 %(42/45)，D组91 %(122/134)。除A组外，C、D二组根除率均高于B组根除率的10 %以上。四个方案组对Hp根除率疗效差异有极显著性，χ²=34.730，P＜0.01。各组与标准方案B组比较，