Meta-Analysis
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2024; 30(6): 579-598
Published online Feb 14, 2024. doi: 10.3748/wjg.v30.i6.579
Urea breath test for Helicobacter pylori infection in adult dyspeptic patients: A meta-analysis of diagnostic test accuracy
Fabian Fellipe Bueno Lemos, Caroline Tianeze de Castro, Marcel Silva Luz, Gabriel Reis Rocha, Gabriel Lima Correa Santos, Luís Guilherme de Oliveira Silva, Mariana Santos Calmon, Cláudio Lima Souza, Ana Carla Zarpelon-Schutz, Kádima Nayara Teixeira, Dulciene Maria de Magalhães Queiroz, Fabrício Freire de Melo
Fabian Fellipe Bueno Lemos, Marcel Silva Luz, Gabriel Reis Rocha, Gabriel Lima Correa Santos, Luís Guilherme de Oliveira Silva, Mariana Santos Calmon, Cláudio Lima Souza, Fabrício Freire de Melo, Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
Caroline Tianeze de Castro, Instituto de Saúde Coletiva, Universidade Federal da Bahia, Salvador 40110040, Bahia, Brazil
Ana Carla Zarpelon-Schutz, Kádima Nayara Teixeira, Campus Toledo, Universidade Federal do Paraná, Toledo 85919-899, Paraná, Brazil
Dulciene Maria de Magalhães Queiroz, Laboratory of Research in Bacteriology, UFMG, Belo Horizonte 30130-100, Minas Gerais, Brazil
Author contributions: Lemos FFB, Castro CT, Silva Luz M, Queiroz DMM, and Freire de Melo F contributed to the conceptualization of the manuscript; Lemos FFB, Castro CT, Queiroz DMM and Freire de Melo F designed the study methodology; Lemos FFB, Castro CT, Calmon MS, Silva Luz M, Rocha GR, Correa Santos GL, de Oliveira Silva LG, Calmon MS were responsible for manuscript visualization; Lemos FFB, Castro CT, Calmon MS, Silva Luz M, Rocha GR, Correa Santos GL, de Oliveira Silva LG, Calmon MS contributed to the investigation; Lemos FFB, Castro CT, Calmon MS, Silva Luz M, Rocha GR, Correa Santos GL, de Oliveira Silva LG, Calmon MS performed formal analysis; Lemos FFB and Castro CT wrote the original draft; Castro CT and Queiroz DMM were responsible for manuscript editing; Castro CT, Teixeira KN, Souza CL, and Queiroz DMM were responsible for manuscript writing and review; Freire de Melo F supervised the writing of the original draft.
Supported by Scientific Initiation Scholarship Programme (PIBIC) of the Bahia State Research Support Foundation; the Doctorate Scholarship Program of the Coordination of Improvement of Higher Education Personnel; the Scientific Initiation Scholarship Programme (PIBIC) of the National Council for Scientific and Technological Development; and the CNPq Research Productivity Fellowship.
Conflict-of-interest statement: The authors declare no conflict of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Fabrício Freire de Melo, PhD, Professor, Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Estrada do Bem Querer, No. 3293-3391- Candeias, Vitória da Conquista 45029-094, Bahia, Brazil. freiremeloufba@gmail.com
Received: November 14, 2023
Peer-review started: November 14, 2023
First decision: December 5, 2023
Revised: December 16, 2023
Accepted: January 16, 2024
Article in press: January 16, 2024
Published online: February 14, 2024
Processing time: 82 Days and 15.3 Hours
ARTICLE HIGHLIGHTS
Research background

The urea breath test (UBT) has become a widely accepted non-invasive method for detecting Helicobacter pylori (H. pylori). While numerous studies have confirmed its high accuracy, its reliability is often hindered by inherent limitations.

Research motivation

In a previous investigation, the diagnostic accuracy of the UBT, which encompasses both 13C-UBT and 14C-UBT, was evaluated in adult patients with dyspepsia to determine the presence of H. pylori infection. Although the test demonstrated a high degree of precision, its reliability was compromised by significant and unexplained heterogeneity, which persisted even after conducting subgroup analyses. This trend continued in subsequent studies, with similar challenges encountered in determining pooled estimates of diagnostic accuracy for 14C-UBT. Furthermore, a subsequent systematic review revealed that the variability in thresholds and reference standards across studies limited the available data for pooling accuracy measures at specific UBT thresholds. These findings underscore the need for a rigorous statistical synthesis to clarify and reconcile the diagnostic accuracy of the UBT for the diagnosis of H. pylori infection, addressing challenges identified in prior research.

Research objectives

To evaluate and contrast the diagnostic accuracy of 13C-UBT and 14C-UBT for H. pylori infection in adult patients with dyspepsia.

Research methods

We conducted independent searches of PubMed/MEDLINE, EMBASE, and Cochrane Central databases until April 2022, focusing on diagnostic accuracy studies that evaluated at least one of the index tests (13C-UBT or 14C-UBT) against a reference standard. We utilized the QUADAS-2 tool to assess the methodological quality of the studies, and we calculated sensitivity, specificity, positive and negative test likelihood ratios (LR+ and LR-), as well as the diagnostic odds ratio (DOR) and their 95% confidence intervals using the bivariate random-effects model. We conducted subgroup analyses based on urea dosing, time after urea administration, and assessment technique. To investigate a possible threshold effect, we conducted Spearman correlation analysis, and we generated summary receiver operating characteristic (SROC) curves to assess heterogeneity. Lastly, we visually inspected a funnel plot and used Egger’s test to evaluate publication bias.

Research results

A screening of 4621 studies led to the selection of 60 articles for inclusion in a diagnostic test accuracy meta-analysis after full-text reading. Our analysis highlights the superior diagnostic accuracy of 13C-UBT compared to 14C-UBT, as evidenced by higher sensitivity (96.60% vs 96.15%), specificity (96.93% vs 89.84%), likelihood ratios (LR+ 22.00 vs 10.10; LR- 0.05 vs 0.06), and AUC values (0.979 vs 0.968). Particularly noteworthy is the significantly higher DOR of 13C-UBT (586.47) compared to 14C-UBT (DOR 226.50), establishing 13C-UBT as the preferred diagnostic tool for individuals with dyspepsia and H. pylori infection. Correlation analysis indicated no threshold effect for both 13C-UBT (r = 0.48) and 14C-UBT (r = -0.01), and the SROC curves consistently demonstrated accurate performance for both tests. The high AUC values (13C-UBT: 0.979; 14C-UBT: 0.968), nearing 1.00, further affirm the excellent accuracy of both UBT variants, solidifying their reliability as diagnostic tools in clinical practice.

Research conclusions

Our study establishes 13C-UBT as the superior diagnostic approach over 14C-UBT. Furthermore, our findings underscore the critical importance of meticulously considering factors such as urea dosage, assessment timing, and measurement techniques for both tests to optimize diagnostic accuracy. However, it is paramount for researchers and clinicians to thoroughly evaluate the strengths and limitations of our conclusions before integrating them into clinical practice.

Research perspectives

Future research should focus on improving the comprehension, practicality, and dependability of UBTs for H. pylori infection. This endeavor involves refining techniques, examining sources of variability, exploring threshold effects, conducting longitudinal and comparative investigations, addressing biases, and assessing cost-effectiveness.