Background: Helicobacter pylori plays a central role in the development of gastric cancer, and prediction of H pylori infection by visual inspection of the gastric mucosa is an important function of endoscopy. However, there are currently no established methods of optical diagnosis of H pylori infection using endoscopic images. Definitive diagnosis requires endoscopic biopsy. Artificial intelligence (AI) has been increasingly adopted in clinical practice, especially for image recognition and classification. Objective: This study aimed to evaluate the diagnostic test accuracy of AI for the prediction of H pylori infection using endoscopic images. Methods: Two independent evaluators searched core databases. The inclusion criteria included studies with endoscopic images of H pylori infection and with application of AI for the prediction of H pylori infection presenting diagnostic performance. Systematic review and diagnostic test accuracy meta-analysis were performed. Results: Ultimately, 8 studies were identified. Pooled sensitivity, specificity, diagnostic odds ratio, and area under the curve of AI for the prediction of H pylori infection were 0.87 (95% CI 0.72-0.94), 0.86 (95% CI 0.77-0.92), 40 (95% CI 15-112), and 0.92 (95% CI 0.90-0.94), respectively, in the 1719 patients (385 patients with H pylori infection vs 1334 controls). Meta-regression showed methodological quality and included the number of patients in each study for the purpose of heterogeneity. There was no evidence of publication bias. The accuracy of the AI algorithm reached 82% for discrimination between noninfected images and posteradication images. Conclusions: An AI algorithm is a reliable tool for endoscopic diagnosis of H pylori infection. The limitations of lacking external validation performance and being conducted only in Asia should be overcome. Trial Registration: PROSPERO CRD42020175957; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=175957
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