Sequential Combination of Markers May Help Reduce Need for Liver Biopsies in NAFLD

An algorithm combining the fibrosis-4 index (FIB-4) and liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE) sequentially with a lower cutoff to rule out advanced fibrosis and a higher cutoff to rule in cirrhosis can reduce the need for liver biopsies in patients with non-alcoholic fatty liver disease (NAFLD), according to a study in Gut.

Investigators conducted an individual patient data meta-analysis to assess the LSM-VCTE and compare it with the FIB-4 and NAFLD fibrosis score (NFS) in order to develop diagnostic strategies that could reduce the need for liver biopsies. Eligible studies included data on adults with NAFLD and paired liver histology and LSM-VCTE.

The authors of 37 studies provided usable data, and the final dataset included 5735 unique patients. Participants’ median age was 54 years, 2570 (45%) were women, 30% had advanced fibrosis, and 11% had cirrhosis.

The LSM-VCTE, FIB-4, NFS, aspartate aminotransferase (AST)-to-platelet ratio index (APRI), and AST to alanine aminotransferase (ALT) ratio (AST/ALT) had area under the receiver operating characteristic curves of 0.85, 0.76, 0.73, 0.70, and 0.64, respectively, for identifying advanced fibrosis, and 0.90, 0.80, 0.78, 0.72, and 0.69, respectively, for detecting cirrhosis.

The investigators also assessed LSM-VCTE, FIB-4, and NFS to diagnose advanced fibrosis in sequential combinations of serum-based noninvasive tests and LSM-VCTE. With use of threshold combinations for FIB-4 and NFS from published studies (<1.3 and ≥2.67, <1.3 and ≥3.25 for FIB-4; <–1.455 and ≥0.676 for NFS) paired with the best threshold pair for LSM-VCTE (<7.9 kPa and ≥9.6 kPa, which had the highest sensitivity and lowest indeterminate proportion), the proportion of patients in the indeterminate group was 5%. The FIB-4 + LSM-VCTE and NFS + LSM VCTE sequential combinations had a specificity of >80% and a sensitivity of ≤80%.

The cutoffs in the derivation set for 95% and 98% specificity regarding the diagnosis of cirrhosis were 20.4 kPa and 27.6 kPa, respectively, for LSM-VCTE, 3.48 and 4.63, respectively, for FIB-4, and 1.01 and 1.57, respectively, for NFS. These cutoffs were similar in the validation set.

Algorithms that combined FIB-4 (lower cutoff of 1.3 and upper cutoffs of 3.48 and 4.63) and LSM by VCTE (lower cutoff rounded to 8.0 kPa and upper cutoffs rounded to 20.0 kPa and 28.0 kPa) were then compared with the traditional way of using these tests, with rounded cutoffs for LSM by VCTE (8 kPa and 10 kPa). This technique increased the number of patients who needed an LSM from 34% to 40% and 44%. However, it decreased the number of patients who needed a liver biopsy (from 33% to 19% and 24% when using the 95% and 98% specificity cutoffs, respectively).

Among several limitations, the investigators noted that they did not have any data from the United States and had to use locally provided histology results, introducing possible bias. Additionally, they covered a large time period in which the LSM-VCTE application underwent significant changes.

“[O]ur study provides further validation of the use of sequential combination of FIB-4 and LSM-VCTE to rule out patients with NAFLD and advanced fibrosis who can be managed in primary care,” the researchers concluded.

Disclosures: Some of the study authors declared affiliations with pharmaceutical companies. Please see the original reference for a full list of disclosures.

Reference Mózes FE, Lee JA, Selvaraj EA, et al. Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis.Gut. Published online May 17, 2021. doi:10.1136/gutjnl-2021-324243