Gisbert J P, Pajares J M, García-Valriberas R, Abraira V, Boixeda D, García-Grávalos R, Martín-de-Argila C, García-Plaza A
Dept. of Gastroenterology, Hospital de la Princesa, Autonomous University of Madrid, Spain.
Scand J Gastroenterol. 1998 Nov;33(11):1144-51. doi: 10.1080/00365529850172485.
Our aim was to study the incidence of Helicobacter pylori recurrence in our country and to assess the different variables that might influence it.
We studied prospectively 331 duodenal ulcer patients (mean age, 48 +/- 14 years, 71% male) in whom H. pylori had been eradicated. Several therapies were used, classified as low-efficacy (omeprazole + amoxycillin, 32% eradication rate; omeprazole + amoxycillin + metronidazole, 56%) and high-efficacy therapies (omeprazole + clarithromycin + amoxycillin or metronidazole, 88%; bismuth triple therapy, 77%). One month after completion of therapy an endoscopy with biopsies and/or 13C-urea breath test was performed. A breath test was carried out again at 6 months, 1 year, and 2 years, to study H. pylori recurrences. Endoscopy (with biopsies) was performed only to confirm recurrences. Multiple logistic regression analysis was used. Differences between Kaplan-Meier curves were evaluated with the log-rank test.
Sixty-seven patients were followed up for 6 months, 136 for 1 year, and 128 for 2 years, giving 425 patient-years of follow-up. A total of 18 H. pylori recurrences was observed (12 at 6 months, 4 at 1 year, and 2 after 2 years), yielding a yearly recurrence of 4.2% patient-years(-1). The respective risk of H. pylori recurrence for each period was 3.6% (95% confidence interval (CI), 2.1%-6.2%), 1.5% (0.6%-3.8%), and 1.5% (0.4%-5.5%). The probability of being H. pylori-negative at 6 months, 1 year, and 2 years was, respectively, 96.4% (94.4%-98.4%), 94.9% (92.5%-97.4%), and 93.4% (90.3%-96.6%). Duodenal ulcer was found in half of the reinfected patients. The recurrence rate at 6 months was 10.3% (5.7%-18%) in patients <40 years old and only 0.85% (0.2%-3.1%) in those > or =40 years old (P = 0.0002). Of the patients who became reinfected at 6 months 27% (6%-61%) had delta breath test values between 3 per thousand and 5 per thousand 1 month after therapy, whereas only 4.6% (2.7%-7.7%) of non-reinfected patients had delta after eradication > or =3 per thousand (P = 0.0097). H. pylori recurrence at 6 months was 8.2% (4.5%-15%) in patients previously treated with low-efficacy therapies and only 1.7% (0.7%-4.3%) when high efficacy therapies were used (P = 0.0098). In the multivariate analysis age (odds ratio (OR), 0.9; 95% CI, 0.8-0.96; P = 0.0008), the delta breath test value after therapy (OR, 2.2; CI, 1.2-4.1; P = 0.0076), and therapy regimen (OR, 6.4; CI, 1.5-27; P = 0.0109) were the only variables that correlated with H. pylori recurrence at 6 months. Differences were observed when Kaplan-Meier curves were compared, depending on age (<40 or > or =40 years; P = 0.0054), breath test value (delta) 1 month after therapy (<3 or > or =3 per thousand; P = 0.0089), and therapy regimen (high or low efficacy; P = 0.0006).
Risk of post-eradication H. pylori recurrence is higher during the first 6 months, which suggests that most recurrences during this period are recrudescences and not true reinfections. Patients who have H. pylori recurrence tend to be younger and have higher delta 13C-urea breath test values after therapy, which suggests that a 'negative' value between 3 per thousand and 5 per thousand needs to be confirmed. Recurrence of H. pylori is more frequent in patients treated with low-efficacy therapies but is exceptional when high-efficacy therapies are used, in which case post-therapy eradication can be safely confirmed at 4 weeks. Finally, recurrence of H. pylori is clinically relevant, as ulcer recurrence is observed in a considerable proportion of these patients.
我们的目的是研究我国幽门螺杆菌复发的发生率，并评估可能影响其复发的不同变量。
我们前瞻性地研究了331例幽门螺杆菌已被根除的十二指肠溃疡患者（平均年龄48±14岁，71%为男性）。使用了几种治疗方法，分为低疗效治疗（奥美拉唑+阿莫西林，根除率32%；奥美拉唑+阿莫西林+甲硝唑，根除率56%）和高疗效治疗（奥美拉唑+克拉霉素+阿莫西林或甲硝唑，根除率88%；铋剂三联疗法，根除率77%）。治疗结束1个月后进行内镜检查及活检和/或¹³C-尿素呼气试验。在6个月、1年和2年时再次进行呼气试验，以研究幽门螺杆菌的复发情况。仅在内镜检查（及活检）时用于确认复发。采用多因素逻辑回归分析。用对数秩检验评估Kaplan-Meier曲线之间的差异。
67例患者随访6个月，136例随访1年，128例随访2年，共随访425患者年。共观察到18例幽门螺杆菌复发（6个月时12例，1年时4例，2年后2例），年复发率为4.2%患者年⁻¹。各时间段幽门螺杆菌复发的风险分别为3.6%（95%置信区间（CI），2.1% - 6.2%）、1.5%（0.6% - 3.8%）和1.5%（0.4% - 5.5%）。6个月、1年和2年时幽门螺杆菌阴性的概率分别为96.4%（94.4% - 98.4%）、94.9%（92.5% - 97.4%）和93.4%（90.3% - 96.。6%）。一半的再感染患者发现有十二指肠溃疡。年龄<40岁的患者6个月时的复发率为10.3%（5.7% - 18%），而年龄≥40岁的患者仅为0.85%（0.2% - 3.1%）（P = 0.0002）。在6个月时再感染的患者中，27%（6% - 61%）在治疗后1个月的δ呼气试验值在3‰至5‰之间，而未再感染的患者中只有4.6%（2.7% - 7.7%）在根除后δ≥3‰（P = 0.0097）。先前接受低疗效治疗的患者6个月时幽门螺杆菌复发率为8.2%（4.5% - 15%）。，而使用高疗效治疗时仅为1.7%（0.7% - 4.3%）（P = 0.0098）。在多因素分析中，年龄（比值比（OR），0.9；95%CI，0.8 - 0.96；P = 0.0008）、治疗后δ呼气试验值（OR，2.2；CI，1.2 - 4.1；P = 0.0076）和治疗方案（OR，6.4；CI，1.5 - 27；P = 0.0109）是与6个月时幽门螺杆菌复发相关的仅有的变量。根据年龄（<40岁或≥40岁；P = 0.0054）、治疗后1个月的呼气试验值（δ）（<3‰或≥3‰；P = 0.0089）和治疗方案（高疗效或低疗效；P = 0.0006）比较Kaplan-Meier曲线时观察到差异。
根除后幽门螺杆菌复发的风险在前6个月较高，这表明在此期间的大多数复发是复发而非真正的再感染。幽门螺杆菌复发的患者往往较年轻，治疗后¹³C-尿素呼气试验的δ值较高，这表明3‰至5‰之间的“阴性”值需要确认。幽门螺杆菌在接受低疗效治疗的患者中复发更频繁，但在使用高疗效治疗时则很少见，在这种情况下，治疗后4周可安全确认根除情况。最后幽门螺杆菌复发具有临床相关性，因为在相当一部分这些患者中观察到溃疡复发。
