Szakács Zsolt, Mátrai Péter, Hegyi Péter, Szabó Imre, Vincze Áron, Balaskó Márta, Mosdósi Bernadett, Sarlós Patrícia, Simon Mária, Márta Katalin, Mikó Alexandra, Pécsi Dániel, Demcsák Alexandra, Bajor Judit
Institute for Translational Medicine, University of Pécs, Pécs, Hungary.
Institute of Bioanalysis, University of Pécs, Pécs, Hungary.
PLoS One. 2017 Nov 2;12(11):e0187526. doi: 10.1371/journal.pone.0187526. eCollection 2017.
Persistent intestinal damage is associated with higher complication rates in celiac disease. We aimed to assess the potential modifiers of mucosal recovery.
We screened databases (PubMed, Embase, Cochrane Trials, and Web of Science) for papers on celiac disease. Papers discussing (1) celiac patients (2) follow-up biopsy and (3) mucosal recovery after commencement of a gluten-free diet were included. The primary outcome was to produce a comprehensive analysis of complete mucosal recovery (i.e., Marsh 0 on follow-up). We compared children's recovery ratios to those of adults. Patients following a strict gluten-free dietary regimen were included in a subgroup. Summary point estimates, 95% confidence intervals (CIs), and 95% predictive intervals (PIs) were calculated. Heterogeneity was tested with I2-statistic. The PROSPERO registration number is CRD42016053482.
The overall complete mucosal recovery ratio, calculated from 37 observational studies, was 0.36 (CI: 0.28-0.44, PI: -0.12-0.84; I2: 98.4%, p<0.01). Children showed higher complete mucosal recovery ratio than adults (p<0.01): 0.65 (CI: 0.44-0.85, PI: -0.10-1.39; I2: 96.5%, p<0.01) as opposed to 0.24 (CI: 0.15-0.33, PI: -0.19-1.08; I2: 96.3%, p<0.01). In the strict dietary adherence subgroup, complete mucosal recovery ratio was 0.47 (CI: 0.24-0.70, PI: -0.47-1.41; I2: 98.8%, p<0.001). On meta-regression, diagnostic villous atrophy (Marsh 3) ratio (-8.97, p<0.01) and male ratio (+6.04, p<0.01) proved to be a significant determinant of complete mucosal recovery, unlike duration of gluten-free diet (+0.01, p = 0.62). The correlation between complete mucosal recovery ratio and age on diagnosis is of borderline significance (-0.03, p = 0.05).
There is considerable heterogeneity across studies concerning complete mucosal recovery ratios achieved by a gluten-free diet in celiac disease. Several celiac patients fail to achieve complete mucosal recovery even if a strict dietary regimen is followed. Younger age on diagnosis, less severe initial histologic damage and male gender predispose for achieving mucosal recovery.
持续性肠道损伤与乳糜泻较高的并发症发生率相关。我们旨在评估黏膜恢复的潜在影响因素。
我们在数据库(PubMed、Embase、Cochrane试验库和科学网)中筛选有关乳糜泻的论文。纳入讨论(1)乳糜泻患者、(2)随访活检以及(3)无麸质饮食开始后黏膜恢复情况的论文。主要结局是对完全黏膜恢复(即随访时Marsh 0级)进行全面分析。我们将儿童的恢复率与成人的进行比较。遵循严格无麸质饮食方案的患者纳入一个亚组。计算汇总点估计值、95%置信区间(CI)和95%预测区间(PI)。用I²统计量检验异质性。PROSPERO注册号为CRD42016053482。
根据37项观察性研究计算得出的总体完全黏膜恢复率为0.36(CI:0.28 - 0.44,PI: - 0.12 - 0.84;I²:98.4%,p < 0.01)。儿童的完全黏膜恢复率高于成人(p < 0.01):为0.65(CI:0.44 - 0.85,PI: - 0.10 - 1.39;I²:96.5%,p < 0.01),而成人则为0.24(CI:0.15 - 0.33,PI: - 0.19 - 1.08;I²:96.3%,p < 0.01)。在严格饮食依从性亚组中,完全黏膜恢复率为0.47(CI:0.24 - 0.70,PI: - 0.47 - 1.41;I²:98.8%,p < 0.001)。在Meta回归分析中,诊断时绒毛萎缩(Marsh 3级)比例(-8.97,p < 0.01)和男性比例(+6.04,p < 0.01)被证明是完全黏膜恢复的重要决定因素,与无麸质饮食持续时间(+0.01,p = 0.62)不同。完全黏膜恢复率与诊断时年龄之间的相关性具有临界显著性(-0.03,p = 0.05)。
关于乳糜泻患者通过无麸质饮食实现的完全黏膜恢复率,各研究之间存在相当大的异质性。即使遵循严格的饮食方案,仍有一些乳糜泻患者无法实现完全黏膜恢复。诊断时年龄较小、初始组织学损伤较轻以及男性性别更易实现黏膜恢复。