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

Abstract

ObjectiveLiver 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.DesignIndividual 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.ResultsData 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.ConclusionSequential 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.

Diagnostic Modalities of Non-Alcoholic Fatty Liver Disease: From Biochemical Biomarkers to Multi-Omics Non-Invasive Approaches

“…After multivariate analysis, the model included age, BMI, AST/ALT ratio, platelet count, hyperglycaemia and albumin as significant factors. The proposed formula is shown [ 110 ] in the equation: NFS = −1.675 + 0.037 × age (years) + 0.094 × BMI (kg/m 2 ) + 1.13 × impaired fasting glycemia (IFG) or diabetes (yes = 1, no = 0) + 0.99 × AST/ALT ratio − 0.013 × platelet (×109/L) − 0.66 × albumin (g/dL). A score below −1.455 would be inconsistent with significant fibrosis, whilst a score above 0.676 can diagnose advanced fibrosis.…”

“…Therefore, with this model, only the patients with indeterminate results, i.e., 25% of patients, would require a liver biopsy. In a meta-analysis of 37 studies, Mózes et al reported the AUROC of NFS to be 0.73 [ 110 ]. One of the main limitations of the test is how BMI might be interpreted differently in different ethnic groups.…”

Progressive Liver Fibrosis in Non-Alcoholic Fatty Liver Disease

“…However, a key disadvantage is its propensity to overestimate fibrosis in alcohol users, due to its heavy reliance on AST [ 95 ]. Nonetheless, FIB-4 has been found to increase sensitivity of fibrosis detection and decrease the needs for liver biopsies, especially when combined with imaging-based biomarkers, such as liver stiffness measurement (LSM) detected by acoustic resonance form impulse (ARFI) and vibration controlled transient elastography (VCTE) [ 96 ].…”

MAFLD/NAFLD Biopsy-Free Scoring Systems for Hepatic Steatosis, NASH, and Fibrosis Diagnosis

“…Moreover, studies have shown that these systems may avoid up to 38-80% of liver biopsies (29,30). Currently, no single marker has been used for the precise detection of MAFLD/NAFLD, as isolated biomarkers do not provide sufficiently accurate information for diagnosis (31)(32)(33). However, when coupled with clinical features and with each other, accurate diagnosis, staging, and prognosis for this disease become possible (34).…”