Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis.

Mózes, Ferenc Emil; Lee, Jenny A; Selvaraj, Emmanuel Anandraj; Jayaswal, Arjun Narayan Ajmer; Trauner, Michael; Boursier, Jerome; Fournier, Céline; Staufer, Katharina; Stauber, Rudolf E; Bugianesi, Elisabetta; Younes, Ramy; Gaia, Silvia; Lupșor-Platon, Monica; Petta, Salvatore; Shima, Toshihide; Okanoue, Takeshi; Mahadeva, Sanjiv; Chan, Wah-Kheong; Eddowes, Peter J; Hirschfield, Gideon M; ... (2022). Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis. Gut, 71(5), pp. 1006-1019. BMJ Publishing Group 10.1136/gutjnl-2021-324243

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Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Index (FIB-4) and NAFLD (non-alcoholic fatty liver disease) Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies.


Individual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individually and in sequential combinations.


Data were included from 37 primary studies (n=5735; 45% women; median age: 54 years; median body mass index: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (<1.3; ≥2.67) followed by LSM-VCTE cut-offs (<8.0; ≥10.0 kPa) to rule-in or rule-out advanced fibrosis had sensitivity and specificity (95% CI) of 66% (63-68) and 86% (84-87) with 33% needing a biopsy to establish a final diagnosis. FIB-4 cut-offs (<1.3; ≥3.48) followed by LSM cut-offs (<8.0; ≥20.0 kPa) to rule out advanced fibrosis or rule in cirrhosis had a sensitivity of 38% (37-39) and specificity of 90% (89-91) with 19% needing biopsy.


Sequential combinations of markers with a lower cut-off to rule-out advanced fibrosis and a higher cut-off to rule-in cirrhosis can reduce the need for liver biopsies.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine

UniBE Contributor:

Staufer, Katharina


600 Technology > 610 Medicine & health




BMJ Publishing Group




Rahel Fuhrer

Date Deposited:

26 Oct 2021 17:18

Last Modified:

05 Dec 2022 15:53

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

biostatistics clinical decision making fatty liver hepatic fibrosis





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