Comparison of non-invasive fibrosis markers and classical liver biopsy in chronic hepatitis C
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Updated: May 26, 2026

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Published on: July 21, 2023
1Department of Infectious Diseases and Clinical Microbiology, Eskisehir Osmangazi University, Eskisehir, Turkey.
Insights
Non-invasive serum biomarkers like FibroTest and FIB4 show promise in diagnosing significant liver fibrosis in chronic hepatitis C patients. While not replacing liver biopsy, they can help exclude advanced fibrosis with high negative predictive values.
Area of Science:
- Hepatology
- Biomarker Discovery
- Diagnostic Accuracy
Background:
- Chronic hepatitis C (HCV) infection can lead to liver fibrosis and cirrhosis.
- Liver biopsy, the gold standard for staging fibrosis, is invasive.
- Non-invasive biomarkers are sought to improve fibrosis assessment.
Purpose of the Study:
- To compare the diagnostic performance of nine non-invasive serum biomarkers against liver biopsy for staging liver fibrosis in treatment-naive HCV patients.
- To evaluate the utility of these biomarkers in identifying significant fibrosis (F3-F4).
Main Methods:
- Seventy-seven treatment-naive, HCV genotype 1 patients were enrolled across 14 centers.
- Nine serum biomarkers were calculated: platelet count, AST/ALT ratio (AAR), cirrhosis discriminate score (CDS), FIB4, AST/platelet ratio index (APRI), age-platelet (AP) index, Göteborg University cirrhosis index (GUCI), FibroTest, and ActiTest.
- Biomarker results were correlated with histological findings (ISHAK fibrosis score).
Main Results:
- Most serum biomarkers, excluding AAR, showed weak to moderate correlation with liver biopsy results.
- FibroTest, FIB4, APRI, and AP index demonstrated significant differences between early (F0-F2) and advanced (F3-F4) fibrosis stages.
- Negative predictive values (NPVs) for advanced fibrosis (F3-F4) were high: 95% for FibroTest, 85% for FIB4, 85% for APRI, and 83% for AP index.
Conclusions:
- Non-invasive serum biomarkers can aid in diagnosing significant liver fibrosis but are insufficient for detecting early-stage fibrosis.
- FibroTest, FIB4, APRI, and AP index are valuable tools for excluding significant fibrosis in chronic HCV patients, offering >80% NPV.
Abstract:
The aim of this study was to compare the results of nine non-invasive serum biomarkers with liver biopsies to predict liver fibrosis stage. HCV-RNA-positive, HCV genotype 1, treatment-naive patients with chronic HCV infections were included from 14 centers (n=77). The platelet count, AST/ALT ratio (AAR), cirrhosis discriminate score (CDS), FIB4, AST/platelet ratio index (APRI), age-platelet (AP) index, Göteborg University cirrhosis index (GUCI), FibroTest, and ActiTest were calculated and compared to histologic findings. All serum biomarkers, except AAR, were weakly or moderately correlated with liver biopsy results (ISHAK fibrosis score). The mean scores of FibroTest, FIB4, APRI, and AP index were significantly different between F0-F2 and F3-F4 groups and the negative predictive values (NPVs) of the F3-F4 group were 95%, 85%, 85%, and 83%, respectively, for these serum biomarkers. Our study suggests that serum biomarkers may help to diagnose significant fibrosis but inadequate to detect fibrosis in early stages. Although liver biopsy is still the gold standard to diagnose liver fibrosis, FibroTest, FIB4, APRI, or AP index may be used to exclude significant fibrosis with >80% NPV.
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