Prediction of Chronic Atrophic Gastritis and Gastric Neoplasms by Serum Pepsinogen Assay: A Systematic Review and Meta-Analysis of Diagnostic Test Accuracy

Abstract

Serum pepsinogen assay (sPGA), which reveals serum pepsinogen (PG) I concentration and the PG I/PG II ratio, is a non-invasive test for predicting chronic atrophic gastritis (CAG) and gastric neoplasms. Although various cut-off values have been suggested, PG I ≤70 ng/mL and a PG I/PG II ratio of ≤3 have been proposed. However, previous meta-analyses reported insufficient systematic reviews and only pooled outcomes, which cannot determine the diagnostic validity of sPGA with a cut-off value of PG I ≤70 ng/mL and/or PG I/PG II ratio ≤3. We searched the core databases (MEDLINE, Cochrane Library, and Embase) from their inception to April 2018. Fourteen and 43 studies were identified and analyzed for the diagnostic performance in CAG and gastric neoplasms, respectively. Values for sensitivity, specificity, diagnostic odds ratio, and area under the curve with a cut-off value of PG I ≤70 ng/mL and PG I/PG II ratio ≤3 to diagnose CAG were 0.59, 0.89, 12, and 0.81, respectively and for diagnosis of gastric cancer (GC) these values were 0.59, 0.73, 4, and 0.7, respectively. Methodological quality and ethnicity of enrolled studies were found to be the reason for the heterogeneity in CAG diagnosis. Considering the high specificity, non-invasiveness, and easily interpretable characteristics, sPGA has potential for screening of CAG or GC.

Keywords: atrophic; gastric neoplasms; gastritis; pepsinogens.

Figure 1

Flow diagram of the identification of relevant studies. (A) For the diagnosis of CAG, (B) For the diagnosis of gastric neoplasm. PG, pepsinogen; CAG, chronic atrophic gastritis.

Figure 1

Flow diagram of the identification of relevant studies. (A) For the diagnosis of CAG, (B) For the diagnosis of gastric neoplasm. PG, pepsinogen; CAG, chronic atrophic gastritis.

Figure 2

QUADAS-2 for the assessment of the methodological qualities of all the enrolled studies for the diagnosis of CAG. (+) denotes low risk of bias, (?) denotes unclear risk of bias, (–) denotes high risk of bias. QUADAS-2, Quality Assessment of Diagnostic Accuracy Studies-2; CAG, chronic atrophic gastritis.

Figure 3

QUADAS-2 for the assessment of the methodological qualities of all the enrolled studies for the diagnosis of gastric neoplasm. (+) denotes low risk of bias, (?) denotes unclear risk of bias, (–) denotes high risk of bias. QUADAS-2, Quality Assessment of Diagnostic Accuracy Studies-2.

Figure 4

Forest plots of sensitivity and specificity for the diagnosis of CAG. (A) cut-off value with PG I ≤70 ng/mL and PG I/PG II ratio ≤3, (B) cut-off value with PG I/PG II ratio ≤3. CAG, chronic atrophic gastritis; PG, pepsinogen.

Figure 5

SROC curve with 95% confidence region and prediction region for the diagnosis of CAG. (A) cut-off value with PG I ≤70 ng/mL and PG I/PG II ratio ≤3, (B) cut-off value with PG I/PG II ratio ≤3. SROC, summary receiver operating characteristic; CAG, chronic atrophic gastritis; PG, pepsinogen; SENS, sensitivity; SPEC, specificity; AUC, area under the curve.

Figure 6

Fagan’s normogram for the diagnosis of CAG. (A) cut-off value with PG I ≤70 ng/mL and PG I/PG II ratio ≤3, (B) cut-off value with PG I/PG II ratio ≤3. CAG, chronic atrophic gastritis; PG, pepsinogen; LR, likelihood raio.

Figure 7

Forest plots of sensitivity and specificity for the diagnosis of GC. (A) cut-off value with PG I ≤70 ng/mL and PG I/PG II ratio ≤3, (B) cut-off value with PG I ≤70 ng/mL, (C) cut-off value with PG I/PG II ratio ≤3. GC, gastric cancer; PG, pepsinogen.

Figure 7

Forest plots of sensitivity and specificity for the diagnosis of GC. (A) cut-off value with PG I ≤70 ng/mL and PG I/PG II ratio ≤3, (B) cut-off value with PG I ≤70 ng/mL, (C) cut-off value with PG I/PG II ratio ≤3. GC, gastric cancer; PG, pepsinogen.

Figure 8

SROC curve with 95% confidence region and prediction region for the diagnosis of GC. (A) cut-off value with PG I ≤70 ng/mL and PG I/PG II ratio ≤3, (B) cut-off value with PG I ≤70 ng/mL, (C) cut-off value with PG I/PG II ratio ≤3. SROC, summary receiver operating characteristic; GC, gastric cancer; PG, pepsinogen.

Figure 9

Fagan’s normogram for the diagnosis of GC. (A) cut-off value with PG I ≤70 ng/mL and PG I/PG II ratio ≤3, (B) cut-off value with PG I ≤70 ng/mL, (C) cut-off value with PG I/PG II ratio ≤3. GC, gastric cancer; PG, pepsinogen; LR, likelihood raio.

Figure 10

Deek’s funnel plot for the diagnosis of GC. (A) cut-off value with PG I ≤70 ng/mL and PG I/PG II ratio ≤3, (B) cut-off value with PG I/PG II ratio ≤3. GC, gastric cancer; PG, pepsinogen.