Prevalence of fibrosis and applicability of lab-based noninvasive tests from primary to tertiary care

Georg Semmler, MD, Paul Thöne, MD, Jan Embacher, MD, Philipp Hruska, MD, Lucie Simonis, MD, Katharina Stopfer, MD, Laurenz Fritz, MD, Fiona Köck, MD, Lorenz Balcar, MD, Benedikt S Hofer, MD, Bernhard Wernly, MD, Sophie Gensluckner, MD, Michael Strasser, MD, Andreas Völkerer, MD, Katrine Lindvig, MD, Prof Maja Thiele, MD, PhD, Sarah Wernly, MD, Robert Winker, MD, Prof Thomas Reiberger, MD, Prof Mattias Mandorfer, MD, Prof Michael Trauner, MD, Prof Christian Datz, MD, Prof Thomas-Mathias Scherzer, MD, and Prof Elmar Aigner, MD.

September 2025

Clinical Gastroenterology & Hepatology

10.1016/j.cgh.2025.09.008

What pressing problem did this study address?

Steatotic liver disease (SLD) is common, but only a small fraction of people with SLD develop liver fibrosis which drives serious complications. Identifying those at higher risk is essential, however, the current screening approaches often fail to identify liver fibrosis.

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What did this study find?

This study analysed over 8,000 individuals to assess the prevalence of liver fibrosis and how well it is detected by blood-based tests, namely FIB-4, LiverPRO, and LiverRiskScore. The study found that liver fibrosis is relatively rare in the general population but more frequent in specialist care, particularly in patients with obesity or type 2 diabetes.

The prevalence of liver fibrosis was between 6-7% in primary and secondary care

LiverPRO had the highest sensitivity and LiverRiskScore had the highest specificity

Both LiverPRO and LiverRiskScore significantly outperformed FIB-4, which is still the most commonly used test

This study underlines that LiverPRO consistently performs better than FIB-4 across different demographics and prevalences.

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Background & Aims

Knowing the prevalence of fibrosis, the accuracy of noninvasive tests, and their applicability in referral strategies of individuals screened or surveilled for steatotic liver disease is crucial for individual and policy decision making.

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Methods

Five cohorts spanning primary to tertiary care between 2016 and 2024 were retrospectively included: individuals from the general population (colonoscopy screening, n = 1185, cohort I; primary care); at-risk individuals with metabolic dysfunction (overweight n = 1333, cohort II; prediabetes, n = 996, cohort III; secondary care); and subjects referred to hepatology clinics (n = 2598/n = 2397, cohort IV/V; tertiary care).

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Results

Mean controlled attenuation parameter was 262 to 294 dB/m, and 41% to 64% showed hepatic steatosis. Suspected fibrosis (liver stiffness measurement [LSM] ≥8 kPa) was found in 6.4% of cohort I, 7.3%/6.8% of cohort II/III, and 21%/30% of cohort IV/V, whereas advanced fibrosis (≥12 kPa) was rare (1.2% in cohort I, 1.4%/0.8% in cohorts II/III, and 12%/17% in cohorts IV/V, respectively). The prevalence of fibrosis was especially high in subjects with obesity or diabetes, but not in overweight or prediabetes. Sensitivity of FIB-4 ≥1.3 for liver stiffness measurement ≥8 kPa was low in primary and secondary care (33%–44%) with simultaneously low positive predictive value (8.3%–12%), and overall low accuracy (area under the precision recall curve [AUPRC], 0.09–0.15). LiverPRO (AUPRC, 0.12–0.24) and LiverRisk score (AUPRC, 0.13–0.24) were numerically more accurate, with LiverPRO being the most sensitive and LiverRisk score the most specific first-line test. In tertiary care, LiverPRO was comparatively accurate, but more sensitive than Fibrosis-4 index.

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Conclusions

Prevalence of fibrosis in contemporary patients with steatotic liver disease was ∼7% in primary/secondary care, being especially pronounced in individuals with diabetes or obesity. LiverPRO and LiverRisk score optimize referral pathways.

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