Systematic review with meta-analysis: Dietary adherence influences normalization of health-related quality of life in coeliac disease

doi:10.1016/j.clnu.2016.04.021

Clinical Nutrition

Volume 36, Issue 2, April 2017, Pages 399-406

https://doi.org/10.1016/j.clnu.2016.04.021 Get rights and content

Summary

Background & aims

Gluten-free diet is the keystone of coeliac disease treatment. Despite adherence, some patients continue to suffer from symptoms that negatively influence health-related quality of life (HRQoL). Therefore we performed a systematic review and meta-analysis to assess the effect of gluten-free diet on HRQoL in coeliac disease. We specifically sought for determinants that negatively influenced HRQoL.

Methods

We systematically searched PubMed, EMBASE, CINAHL, PsycINFO and Cochrane Library for studies assessing HRQoL in untreated or treated adults using validated HRQoL-questionnaires from 1960 to September 2015, comparing HRQoL: (1) before and after gluten-free diet initiation or (2) in patients and non-coeliac controls.

Results

We included eighteen studies and sixteen were suitable for meta-analysis.

Gluten-free diet significantly improves HRQoL, for psychological general well-being (PGWB)-Total (mean difference (MD) 7.34, 95% confidence interval (CI) [1.96; 12.72]; p = 0.008), SF-36 Mental Component Score (MCS) (MD 7.37, 95% CI [1.84; 12.90]; p = 0.009) and SF-36 Physical Component Score (PCS) (MD 5.72, 95% CI [1.50; 9.95]; p = 0.008). Treated patients had similar HRQoL compared with controls for PGWB-Total (MD −0.72, 95% CI [−2.71; 1.27]; p = 0.48), but significantly lower levels for SF-36 MCS (MD −4.09, 95% CI [−6.17; −2.01]; p = 0.0001) and PCS (MD −4.57, 95% CI [−6.97; −2.17]; p = 0.0002). Symptom-detected gluten-free diet adhering patients have lower HRQoL compared with screening-detected patients (MD −3.73, 95% CI [−6.77;−0.69]; p = 0.02) Strict adhering patients have better HRQoL compared with non-strict adhering patients for SF-36 MCS (MD 7.70, 95% CI [4.61; 10.79]; p < 0.00001) and for SF-36 PCS (MD 3.23, 95% CI [1.33; 5.14]; p = 0.0009).

Conclusions

Gluten-free diet significantly improves but does not normalize HRQoL in adults with coeliac disease. Dietary adherence improves HRQoL. Better (self-reported) dietary adherence results in higher HRQoL.

Introduction

The recent years have witnessed a remarkable progress in the understanding of the pathophysiology of coeliac disease. Gluten ingestion triggers a T-cell mediated autoimmune response in genetically susceptible individuals that damages small intestinal mucosa. Enteropathy typically leads to symptoms such as abdominal pain, diarrhea, weight loss and biochemical abnormalities such as iron deficiency and anemia [1], [2]. Because of better awareness in the current era, patients are diagnosed in a much earlier phase of their disease and have less specific symptoms such as fatigue, headache, arthralgia, and myalgia [3]. Eliminating gluten from the diet halts the autoimmune response and eventually leads to mucosal healing in the majority of patients [4]. Initiation of a gluten-free diet resolves symptoms and improves health-related quality of life (HRQoL) in many patients [1], [5], [6]. By contrast, a significant group of patients will continue to report symptoms attributed to coeliac disease despite adhering to a gluten-free diet. This impacts their HRQoL [7], [8].

There is increased appreciation of the added value that comes from understanding health outcomes from the patient's perspective. This has put patients at the centre of treatment decisions. A marker that evaluates the global quality of life of patients is very useful as a outcome measure. HRQoL is a multidimensional concept that includes self-reported measures of physical and mental health and has replaced biochemical markers as primary outcome measure for many disease states [9] (Fig. 1). HRQoL is evaluated through validated questionnaires that measure both positive and negative aspects of life including physical and mental health perceptions such as health risks and conditions, functional status, social support, and socioeconomic status [10], [11]. HRQoL data can be used to measure the risk of treatment (for example, side effects or inconvenience) as well as benefit (remission or cure). This may aid in the identification of subgroups with poor perceived health and assists in developing interventions to improve patient's life.

Thus, in an effort to improve care for patients with coeliac disease, we were interested in the determinants that affect HRQoL in these patients.

Therefore, we undertook a systematic review and meta-analysis to assess the effect of a gluten-free diet on HRQoL in coeliac disease. In addition, we sought to evaluate those determinants that contribute most to HRQoL.

Section snippets

Search strategy and selection criteria

We performed a systematic literature search to identify studies reporting on HRQoL in patients with coeliac disease in PubMed, EMBASE, CINAHL, PsycINFO and The Cochrane Library from January 1960 to 30 September 2015. The following Medical Subject Headings terms were used: “coeliac disease”, “coeliac disease/therapy”, “diet, gluten-free”, “glutens”, “quality of life”, “questionnaires” and “well being” without language restrictions. We expanded the search with the following terms: coeliac sprue,

Results

The study selection process is shown in (Fig. 2). Briefly, the initial search identified 1494 records. Eighteen studies reporting on HRQoL in coeliac disease were included in the review and ultimately 16 articles were suitable for meta-analysis. The studies were published between 2002 and 2015. Quality assessment ranked 12 studies as ‘moderate’ and four as ‘high quality’. Two of the included studies were considered to be of ‘low quality’ (Table S5). The characteristics of the included studies

Prospective studies on the effect of a gluten-free diet

Eight studies, in total 998 patients, provided prospective data on the effect of a gluten-free diet [6], [23], [24], [25], [26], [27], [28], [29] (Table S7). A gluten-free diet significantly improved HRQoL after one year of treatment for PGWB Total (MD 7.34, 95% CI [1.96; 12.72]; p = 0.008), SF-36 MCS (MD 7.37, 95% CI [1.84; 12.90]; p = 0.009) and SF-36 PCS (MD 5.72, 95% CI [1.50; 9.95]; p = 0.008) (Fig. 3). Heterogeneity was high with I² values ranging from 71% to 83%.

Patients on a gluten-free diet versus non-coeliac controls

We found 16 out of the 18

Publication bias

Inspection of funnel plots that arose from our analysis did not allow to assess asymmetry of the estimated effects of the individual studies. The limited studies that could be entered in our funnel plot analysis preclude assessment of publication bias. Indeed funnel plots are thought to be unreliable methods of investigating publication bias, particularly if the number of studies is small (less than 10) [37].

Discussion

In this systematic review, using meta-analysis techniques on a sample of 2728 subjects we found that gluten-free diet significantly improves, but does not normalize HRQoL in coeliac disease. This meta-analysis also establishes that better dietary adherence results in higher HRQoL.

Although HRQoL significantly improves with adherence to a gluten-free diet, coeliac disease patients still have lower SF-36 MCS (MD −4.09) and PCS (MD −4.57) compared to non-coeliac or healthy controls. Heterogeneity

Authorship statement

Guarantor of the article: Jordy PW Burger.

Specific author contributions

JB and BdB conceived the study design, performed the data extraction and analysis, performed the systematic review and drafted the manuscript. JB and BdB contributed equally to this manuscript. JI helped with the data analysis and systematic review and reviewed the manuscript for important intellectual content. PW, MT and JD reviewed the manuscript for important intellectual content. All authors have read and approved the final version of the manuscript.

Conflict of interest

None.

Funding

None.

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Meta-analysesSystematic review with meta-analysis: Dietary adherence influences normalization of health-related quality of life in coeliac disease

Summary

Background & aims

Methods

Results

Conclusions

Introduction

Section snippets

Search strategy and selection criteria

Results

Prospective studies on the effect of a gluten-free diet

Patients on a gluten-free diet versus non-coeliac controls

Publication bias

Discussion

Authorship statement

Specific author contributions

Conflict of interest

Funding

Am J Clin Nutr

Dig Liv Dis

Dig Liv Dis

Eur J Cancer

Injury

Pain

J Clin Epidemiol

J Clin Epidemiol

Dig Liv Dis

Dig Liv Dis

Dig Liv Dis

Dig Liv Dis

Am J Clin Nutr

Celiac disease

NEJM

Trends in the presentation of celiac disease

Am J Med

Histologic follow-up of people with celiac disease on a gluten-free diet: slow and incomplete recovery

Am J Clin Pathol

Impact of gluten withdrawal on health-related quality of life in celiac subjects: an observational case-control study

Digestion

Living with coeliac disease: survey results from the U.S.A

J Hum Nutr Diet

Measuring healthy days: population assessment of health-related quality of life

Meta-analyses
Systematic review with meta-analysis: Dietary adherence influences normalization of health-related quality of life in coeliac disease