EDITORS,
I am confused by the claims by Zagari et al regarding use of the combination pepsinogen (PG), gastrin 17 and anti-Helicobacter pylori antibodies serum assays for diagnosis of atrophic gastritis.1 Their summary result was a sensitivity of 74.7% and specificity of 95.6% with positive and negative likelihood ratios of 16.9 and 0.26, respectively. For some reason, they also discuss the data using positive and negative values which are affected by disease prevalence, whereas likelihood ratios are not. They concluded that the test appeared to be reliable for the diagnosis of atrophic gastritis and may be used for screening subjects or populations at high risk of gastric cancer for atrophic gastritis. The authors also state that, in a population with a pre-test probability of 27%, the panel would miss only nine of every 100 subjects with atrophic gastritis. Given the sensitivity of approximately 75%, this is misleading. With a sensitivity of 74.7%, the false negative rate would be approximately 25%. There would be 27 with atrophy of which only 20 would be diagnosed correctly along with seven false negative and three false positive results. To obtain 100 with atrophic gastritis would require a population of 500 with 100 true positive, 35 false negatives and 15 false positives. For a population of 1000 subjects and a pre-test probability of 27%, the number missed would be 68 of 270; 126 of 500 at a 50% pre-test probability and 177 of 700 at a 70% pre-test probability (http://araw.mede.uic.edu/cgi-bin/testcalc.pl). In all these different groups the number of false positive tests will be low consistent with the high specificity. Other large meta-analyses of pepsinogen testing have reported specificities of 77.3% and 73.2%2 and 58.7% and 73.7%.3
Pepsinogen testing is influenced by many different factors; especially important is H. pylori eradication which markedly reduces its reliability.4 The low specificity is its Achilles heel and reflects the fact that the fall in PG I:II ratio has no sharp cut-off in relation to the proportion with intestinal metaplasia.5 A recent comparison of pepsinogen tests including the one described by Zagari et al found poor performance characteristic for detecting moderate to severe histological corpus atrophy by PG I:II ratio (44%/91%/0.70 for the BioHit test).6 PG testing is our best non-invasive test but is has intrinsic flaws that meta-analysis cannot resolve.
ACKNOWLEDGEMENT
Declaration of personal interests: Dr. Graham is a consultant for RedHill Biopharma regarding novel H. pylori therapies and has received research support for culture of Helicobacter pylori and is the PI of an international study of the use of antimycobacterial therapy for Crohn’s disease. He is also a consultant for BioGaia in relation to probiotic therapy for H. pylori infection and for Takeda in relation to H. pylori therapies.
FUNDING INFORMATION
Dr. Graham is supported in part by the Office of Research and Development Medical Research Service Department of Veterans Affairs, Public Health Service grant DK56338 which funds the Texas Medical Center Digestive Diseases Center.
Footnotes
LINKED CONTENT
This article is linked to Zagari et al and Zagari and Greenwood papers. To view these articles visit https://doi.org/10.1111/apt.14248 and https://doi.org/10.1111/apt.14369.
REF ERENCES
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