Evaluation of blood‐based PRO‐C3 testing as a diagnostic marker for staging liver fibrosis: A systematic review and meta‐analysis

Background and Aim With the global increase in chronic liver disease and cirrhosis, there is an increasing need to identify non‐invasive biomarkers to measure the severity of disease progression while reducing reliance on pathological biopsies. This study aimed to comprehensively evaluate the diagnostic value of PRO‐C3 as a biomarker for staging liver fibrosis in patients with viral hepatitis or fatty liver disease. Methods Articles published until January 6, 2023, were searched in the PubMed, Embase, MEDLINE, Web of Science, and Cochrane Library databases. The Quality Assessment of Diagnostic Accuracy Studies‐2 tool was used to evaluate the quality of the included studies. Pooled sensitivity, specificity, diagnostic odds ratio, and likelihood ratios were integrated using a random‐effects model, and a summary receiver operating characteristic curve was constructed. Publication bias was also detected. Subgroup and meta‐regression analyses, as well as sensitivity analysis, were also performed. Results Fourteen studies with 4315 patients were included. Summary area under the curve of PRO‐C3 for the identification of significant fibrosis (≥ F2) and advanced fibrosis (≥ F3) was 0.80 (95% confidence interval: 0.76–0.83). Subgroup and meta‐regression analyses suggested that disease type and sample size may be the primary factors of heterogeneity in PRO‐C3 diagnosis of ≥ F2, while study design, study sample type, and enzyme‐linked immunosorbent assay kit brand may be the primary sources of heterogeneity in PRO‐C3 diagnosis of ≥ F3. Conclusions PRO‐C3 demonstrated clinically meaningful diagnostic accuracy when used alone as a non‐invasive biomarker for diagnosing the liver fibrosis stage in individuals with viral hepatitis or fatty liver disease.