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Noninvasive tests inaccurate for younger, elderly patients with NAFLD

The aminotransferase/alanine transaminase ratio, NAFLD fibrosis score and Fibrosis-4 score yielded poor accuracy in specificity for advanced fibrosis in adults aged 35 years and younger and elderly adults with nonalcoholic fatty liver disease, per published findings in the American Journal of Gastroenterology.

“With the increasing use of simple noninvasive fibrosis markers to identify patients with advanced liver disease, it is important to recognize and mitigate against any limitations of these tests,” Stuart McPherson, BSc, MBChB, MD, FRCP, of The Liver Unit, Newcastle Upon Tyne Hospitals, U.K., and colleagues wrote.

The researchers evaluated 634 adults with biopsy-proven NAFLD recruited from various European specialist hepatology clinics and divided them into groups based on age: aged 35 years and younger (n = 74); age 36 through 45 years (n = 96); aged 46 through 55 years (n = 197); aged 56 through 64 years (n = 191); and aged 65 years and older (n = 76).

Noninvasive fibrosis scores are used frequently to identify or exclude fibrosis in patients with NAFLD. However, these scores have been validated only for adults aged between 35 and 65 years. The aim of the study was to determine whether age affects the diagnostic performance of the aspartate aminotransferase/alanine transaminase ratio (AST/ALT ratio), Fibrosis-4 (FIB-4) score and NAFLD fibrosis score (NFS) for advanced fibrosis.

Among all age groups, the accuracy of the AST/ALT ratio was lower compared with NFS and FIB-4. All three tests performed below standards in the diagnosis of advanced fibrosis in patients aged 35 years and younger: area under the receiver operating curve (AUROC) of 0.52 for AST/ALT ratio and NFS, and 0.6 for FIB-4 score. 

Among the groups of patients aged older than 35 years, the AUROCs were similar for advanced fibrosis for both the NFS and FIB-4, with a range of 0.77 to 0.84. However, the specificity for these tests in this age group decreased with age. This led to an observed “unacceptably low” specificity in patients aged 65 years and older for FIB-4 (35%) and NFS (20%), per the researchers.

“As NAFLD is highly prevalent in older patients, it would be particularly advantageous to have an accurate noninvasive test for fibrosis in this age group,” the researchers wrote. “In light of the poor specificity … our results imply that many patients with mild fibrosis will be wrongly classified as having advanced fibrosis and so would undergo additional unnecessary investigations.”

To address this, the researchers derived optimized cutoffs to improve specificity and reduce the false positive rate. After the adoption of a revised threshold (FIB-4 > 2) for elderly patients, the sensitivity increased to 77% and specificity to 70%. Using a new age-adjusted threshold for NFS (> 0.12), the specificity increased to 70% and sensitivity increased to 80% for advanced fibrosis.

The researchers concluded: “This study shows that age has a significant effect on the performance of simple noninvasive fibrosis scores in diagnosing fibrosis.” – by Melinda Stevens

Disclosure: The researchers report no relevant financial disclosures.