TOPLINE

The LiverRisk score (LRS) demonstrated higher accuracy than the fibrosis-4 (FIB-4) index for the identification of moderate or greater fibrosis, as assessed using liver stiffness measurements (LSMs) ≥ 8 and ≥ 10 kPa, across all age groups in the general US population. The FIB-4 index was less accurate, especially in adults younger than 65 years, and many individuals with elevated liver stiffness still had FIB-4 index values < 1.30 (the usual cutoff).

METHODOLOGY

• Primary screening for liver fibrosis has relied on the FIB‑4 index, a noninvasive test that has shown suboptimal accuracy in low-prevalence settings — particularly in younger adults — prompting interest in the LRS, a noninvasive tool developed for use in the general population.
• Using data from the US National Health and Nutrition Examination Survey, researchers conducted a retrospective analysis to compare the accuracy of the LRS with that of the FIB-4 index for the classification of LSMs ≥ 8 and ≥ 10 kPa; LSMs were assessed using vibration-controlled transient elastography (VCTE) by survey health technicians.
• They included 12,050 adults (47.3%-54.2% women) who completed medical examinations, had VCTE data meeting the survey quality criteria, and had complete data for the calculation of the LRS and FIB-4 index and for stratification by BMI and A1c levels between 2017 and 2023.
• LRS values were calculated using a proprietary algorithm on the basis of age; sex; levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase, fasting blood glucose, and total cholesterol; and platelet count. FIB-4 index values were calculated on the basis of age, levels of ALT and AST, and platelet count; serum glucose measurements were used in this study.
• Outcomes were evaluated across three age groups (18-34, 35-64, and 65 years or above) and metabolic risk factor profiles (all adults, those with BMI ≥ 30, and those with A1c levels ≥ 5.7%).

TAKEAWAY

• For LSM ≥ 8 kPa (n = 1310), the area under the curve (AUC) for the LRS ranged from 0.662 at ages of 18-34 years to 0.711 at ages of 35-64 years, compared with the AUC for the FIB-4 index ranging from 0.510 to 0.591 (P < .0001 for all age groups).
• For LSM ≥ 10 kPa (n = 724), the LRS demonstrated an AUC of 0.669 at ages of 18-34 years, 0.744 at ages of 35-64 years, and 0.712 at ages of 65 years or above, all statistically significantly improved compared with the FIB-4 index (P < .01 for all).
• At ages of 35-64 and 65 years or above, classification accuracy of both the LRS and FIB-4 index remained generally consistent between all adults and subgroups with metabolic risk factors, but both scores showed improved performance in younger adults (18-34 years) with BMI ≥ 30 and further improvement in those with A1c levels ≥ 5.7%.
• The median FIB-4 index values for cases of both LSM ≥ 8 and ≥ 10 kPa were < 1.30 in all age groups except 65 years or above, indicating that the commonly used rule-out cutoff would exclude the majority of elevated LSM cases in younger populations.

IN PRACTICE

“In this analysis, the LRS demonstrated improved accuracy vs the FIB-4 for identification of adults with moderate or greater fibrosis who may benefit from novel interventions. The improved accuracy of the LRS was apparent in all age groups, and particularly notable at younger ages, at which accuracy of the FIB-4 is recognized to be lacking,” the authors of the study wrote.

SOURCE

The study was led by Mary E. Rinella, MD, University of Chicago Pritzker School of Medicine, Chicago. It was published online in Digestive and Liver Disease.

LIMITATIONS

The study used secondary survey data, which may have introduced response and nonresponse biases. The researchers only included people with complete data available. Small sample sizes in the younger adult group (18-34 years) may have masked differences in subgroup analyses.

DISCLOSURES

The study was funded by Madrigal Pharmaceuticals. Some authors disclosed receiving consulting fees from the funding company and other pharmaceutical and biotech companies. Three authors reported being current or previous employees of Madrigal Pharmaceuticals and/or owning stock/stock options in the company.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.