A systematic review and meta-analysis of the accuracy and methodology of the 13C mixed triglyceride breath test for the evaluation of pancreatic function

Abstract

Introduction: The diagnosis of pancreatic exocrine insufficiency (PEI) is challenging. The ¹³C mixed triglyceride breath test (¹³C MTGT) has emerged as a promising diagnostic method. However, there is need to assimilate high quality evidence to understand its accuracy and address variation in the conduct of the test. This systematic review aims to appraise the existing literature on the methodology and accuracy of the ¹³C MTGT.

Methods: A systematic literature search of PUBMED, MEDLINE, and EMBASE databases identified articles describing the use of the ¹³C MTGT in the analysis of pancreatic function in adults. Data extraction addressed each methodological step in detail. These were combined in a narrative synthesis. For quantitative analysis, those studies within this search that assessed the accuracy of the ¹³C MTGT were selected.

Results: 37 studies were included for qualitative review, 6 assessed sensitivity and specificity of the ¹³C MTGT against another measure of PEI and were included in quantitative synthesis. Areas with a majority consensus were pre-test overnight fasting, a test meal with a lipid load of at least 10 g, within-test control of exercise and dietary intake, breath sampling every 30 min and the preference of isotope ratio mass spectrometry (IRMS) for analysis. Good evidence suggests there is no benefit to extend the total timeframe of breath sampling beyond 6 h. Areas of uncertainty are a) Duration of PERT cessation b) the addition of metoclopramide, c) the ideal test meal and d) if the time frame can be shortened. Quantitative analysis among 6 studies demonstrated a pooled sensitivity and specificity of the ¹³C MTGT for diagnosing PEI of 0.84 (95% CI: 0.73-0.91) and 0.87 (95% CI: 0.79-0.93) respectively.

Conclusion: There is yet to emerge a clear standard of breath test methodology that is validated for all causes of PEI and suitable for routine use. The accuracy of the ¹³C MTGT for diagnosing PEI is encouraging when compared to other measures. We present a suggested set protocol based on the current literature and identify areas that need further, high quality evidence. With refinement, the ¹³C MTGT could become a valuable, non-invasive PEI diagnostic tool that could be used outside of specialist centres.

Keywords: 13C breath Test; Exocrine pancreatic insufficiency; Pancreatic function.