Diagnostic accuracy of blood-based non-invasive tests for prediction of varices in pediatric portal-hypertension: A systematic review and meta-analysis

Abstract

BACKGROUND

Portal hypertension (PHT) in children is associated with a high risk of esophageal/gastric varices (EV), which may result in life-threatening upper gastrointestinal bleeding, particularly in those with clinically significant varices (CSV). Upper gastrointestinal endoscopy (UGIE) is reference standard for variceal detection, but is invasive, resource-intensive, and often requires anaesthesia in children. Non-invasive imaging modalities, such as liver and splenic stiffness measurements, show promise but have limited availability and feasibility, particularly in resource-limited settings. Blood-based non-invasive tests represent an attractive alternative; however, their diagnostic performance in children has not been comprehensively synthesised.

AIM

To systematically evaluate and meta-analyse diagnostic accuracy of blood-based non-invasive tests for predicting EV and CSV in pediatric PHT.

METHODS

We conducted a systematic review and diagnostic accuracy meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies guidelines. PubMed, EMBASE, and Scopus were searched from inception to October 2025. Studies evaluating aminotransferase-to-platelet ratio index (APRI), platelet count, clinical prediction rule (CPR), varices prediction rule (VPR), or King’s variceal prediction score (K-VaPS) against UGIE in children (≤ 18 years) with PHT were included. Hierarchical summary receiver operating characteristic models were used to pool sensitivity, specificity, diagnostic odds ratios, and area under the curve (AUC). Subgroup, sensitivity, and publication bias analyses were performed.

RESULTS

Twenty-four studies were included [APRI-17 studies (n = 1355), platelet count-11 studies (n = 1040), CPR-12 studies (n = 944), VPR-7 studies (n = 655), K-VaPS-5 studies (n = 315)]. APRI demonstrated pooled sensitivities and specificities of 0.77 and 0.71 for EV and 0.72 and 0.61 for CSV, with corresponding AUCs of 0.795 and 0.776, respectively. Platelet count showed pooled sensitivities and specificities of 0.69 and 0.77 for EV and 0.66 and 0.72 for CSV, with AUCs of 0.834 and 0.714, respectively. Among prediction scores, VPR showed highest accuracy for CSV prediction (AUC = 0.864), followed by K-VaPS (0.727) and CPR (0.717). Substantial heterogeneity was observed across most of the analyses. Diagnostic accuracy was consistently higher in biliary atresia–exclusive cohorts and Asian populations. The certainty of evidence ranged from moderate to very low.

CONCLUSION

Blood-based non-invasive tests demonstrate moderate accuracy for predicting varices in pediatric PHT and may serve as adjunctive triage tools; however, standardized pediatric thresholds and prospective validation are urgently needed.

Keywords: Pediatric; Portal hypertension; Platelet count; Aspartate aminotransferase to platelet ratio index; Liver cirrhosis; Varices; Clinically significant varices; Non-invasive tests

Core Tip: Blood-based non-invasive tests offer a pragmatic approach for risk stratification of varices in children with portal hypertension. This meta-analysis reveals that commonly used indices, such as aminotransferase-to-platelet ratio index, platelet count, demonstrate moderate diagnostic accuracy and may help identify children at lower risk who could safely defer immediate endoscopic surveillance. Their advantages include wide availability, low cost, and ease of repeat testing, making them particularly relevant in resource-limited settings. However, substantial heterogeneity, variability in applied cut-off thresholds, and low-to-moderate certainty of evidence limit their reliability as standalone tools. Prospective pediatric studies with standardised and aetiology-specific cut-offs are essential before implementing routine guidelines.