Younger age at diagnosis predisposes to mucosal recovery in celiac disease on a gluten-free diet: A meta-analysis

PLoS One. 2017 Nov 2;12(11):e0187526. doi: 10.1371/journal.pone.0187526. eCollection 2017.


Background and aims: Persistent intestinal damage is associated with higher complication rates in celiac disease. We aimed to assess the potential modifiers of mucosal recovery.

Materials and methods: 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.

Results: 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).

Conclusions: 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.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Age Factors*
  • Celiac Disease / diet therapy*
  • Celiac Disease / pathology
  • Child
  • Child, Preschool
  • Diet, Gluten-Free*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mucous Membrane / pathology*

Grant support

This work was supported by the Economic Development and Innovation Operative Programme Grant of the National Research, Development and Innovation Office (GINOP 2.3.2-15-2016-00048) STAY ALIVE grant and by the ÚNKP-17-3-I, ÚNKP-17-3-II New National Excellence Program of the Ministry of Human Capacities.