FIB-4 Plus VCTE Effective for Liver Fibrosis Risk Stratification in Type 2 Diabetes

A two-step noninvasive care pathway using the Fibrosis-4 index (FIB-4) followed by liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) effectively stratifies patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD) into liver-related event (LRE) risk groups, according to findings published in Gut. A separate cross-sectional study presented at the European Association for the Study of the Liver Steatotic Liver Disease (EASL SLD) Summit 2026 similarly found that fibrosis risk stratification with FIB-4 and VCTE is effective in older outpatients with T2D.

In the cross-sectional study, researchers retrospectively enrolled 1203 older outpatients with T2D who had VCTE with LSM and controlled attenuation parameter (CAP) assessment. MASLD was defined as having CAP of 248 dB/m or higher, significant liver fibrosis as LSM of 8 kPa or higher, compensated advanced chronic liver disease (cACLD) as LSM 10 kPa or higher, and clinically significant portal hypertension (CSPH) as LSM of 25 kPa or higher or LSM of 20 kPa or higher and platelet count lower than 150,000/mm3. Prevalence rates of MASLD, significant liver fibrosis, cACLD, and CSPH were 71.3%, 21.1%, 11.7%, and 1.7%, respectively.

Using the FIB-4 index and VCTE as a screening strategy for liver fibrosis, among patients with a normal FIB-4 index, 629 (83.3%) had LSM lower than 8 kPa and 126 (16.7%) had LSM of 8 kPa or higher. The sensitivity, specificity, negative predictive value, and positive predictive value of the FIB-4 index for identifying LSM of 8 kPa or higher were 50.4%, 66.3%, 83.3%, and 28.6%, respectively. An increased body weight (adjusted odds ratio [OR], 3.34; 95% CI, 1.75-6.39) and higher alanine transaminase levels (adjusted OR, 1.54; 95% CI, 1.01-2.36) had the best prediction rate for significant liver fibrosis.

"MASLD and significant liver fibrosis are common in older patients with T2DM," the study authors stated. "Fibrosis risk stratification using FIB-4, followed by VCTE, is a good strategy in real-world settings. However, relying solely on FIB-4 may fail to identify some patients with advanced disease, particularly those with increased body weight and elevated serum aminotransferase levels."

In the study published in Gut, the VCTE-Prognosis Study Group, Liver Health Consortium in China (CHESS), and Diabetes Liver Integrated Management (DLIM) Consortium enrolled patients (n=352) with T2D at 7 sites in China between 2017 and 2024 to undergo FIB-4, VCTE, and liver biopsy. Patients (n=4429) with T2D and MASLD were enrolled at 16 sites in the United States, Europe, and Asia between 2004 and 2023 to undergo FIB-4 and VCTE. The 2-step care pathway recommended all patients to undergo FIB-4 and the subset of patients with a FIB-4 between 1.3 and 2.67 to undergo VCTE.

At biopsy, the patients were graded as having fibrosis stage F0 (11.4%), F1 (43.8%), F2 (22.7%), F3 (15.3%), and F4 (6.8%). In the noninvasive tests, they had a median FIB-4 of 1.3 (IQR, 0.8-2.2) and LSM of 8.2 (IQR, 6.1-12.0) kPa. During a median follow-up of 51.3 months, 3.2% of the noninvasive cohort had a LRE of hepatic decompensation (2.5%) and hepatocellular carcinoma (HCC; 1.3%).

In the noninvasive cohort, FIB-4 classified patients as having low (57.4%), intermediate (29.5%), and high (13.1%) risk and among those with intermediate risk, VCTE classified them as having low (51.6%), intermediate (22.9%), and high (25.5%) risk. These groups corresponded to 3- and 5-year LRE cumulative incidence rates of 0.4% and 0.7% for low risk, 0.4% and 0.9% for intermediate risk, and 7.5% and 11.8% for high risk, respectively. The study authors noted that this study likely had higher LRE event rates as would be observed in primary care, as all patients were recruited from referral centers.

"The two-step approach of FIB-4 followed by LSM provides an efficient and practical framework for risk stratification of MASLD-related advanced fibrosis and LREs in patients with T2D," the study authors concluded.