FIB-4 Shows Fair Accuracy for Fibrosis in Chronic Hepatitis B

Key Takeaways

• Among adults with chronic hepatitis B, FIB-4 showed fair discrimination for VCTE-defined significant fibrosis, with AUROC 0.686; at a cut-off above 0.88, sensitivity was 65.42% and specificity was 60.0%.
• APRI performed similarly but slightly lower in adults with chronic hepatitis B, with AUROC 0.660; at a cut-off above 0.32, sensitivity was 63.55%, specificity was 60.0%, PPV was 54.8%, and NPV was 68.3%.
• In adults with chronic hepatitis B, FIB-4 remained associated with significant fibrosis in multivariable analysis, while hemoglobin, albumin, and INR did not remain significant after adjustment, and the authors concluded that these moderate test characteristics could still allow meaningful misclassification.

Lab-based fibrosis scores were higher in patients with VCTE-defined significant fibrosis than in those without, but FIB-4 showed only fair discrimination against VCTE, with an AUROC of 0.686 in a cross-sectional chronic hepatitis B analysis of FIB-4 and APRI versus VCTE. APRI performed slightly lower at AUROC 0.660, and the authors noted that the moderate sensitivity and specificity seen with both scores leave room for clinically relevant misclassification. In this cohort, the data did not support FIB-4 as a standalone replacement for additional staging methods.

This cross-sectional analysis from the Alexandria University Viral Hepatitis Treatment Unit was conducted from January 15 to May 15, 2024, and included 247 adults with chronic hepatitis B after excluding patients with HCV and/or HIV coinfection, blood malignancies, or decompensated cirrhosis. The investigators used VCTE-defined fibrosis staging in the chronic hepatitis B cohort, defining significant fibrosis at 7.25 kPa or higher, advanced fibrosis at 9.3 kPa or higher, and cirrhosis at 12.4 kPa or higher. By those thresholds, 140 patients were classified as F0-F1 and 107 as F2-F4, including 38 with F2, 14 with F3, and 55 with F4.

Compared with patients without significant fibrosis, those in the significant-fibrosis group were older and had lower hemoglobin and albumin and higher INR, while neutrophil-to-lymphocyte ratio did not differ significantly. That directional separation was also reflected in the fibrosis scores, with median FIB-4 of 1.26, IQR 0.75-2.39, versus 0.79, IQR 0.55-1.11, and median APRI of 0.40, IQR 0.23-0.87, versus 0.27, IQR 0.18-0.41. These between-group patterns were consistent with higher noninvasive score values in patients with greater liver stiffness.

In multivariable analysis, FIB-4 remained associated with significant fibrosis with OR 1.558 (95% CI 1.203-2.017; P=0.001), whereas hemoglobin, albumin, and INR did not retain significance after adjustment. At the greater-than-0.88 threshold, FIB-4 had PPV 55.6% and NPV 69.4%, consistent with the overall pattern of moderate discrimination. The authors also described the analysis as single-center, retrospective in data collection, and based on VCTE rather than biopsy, and they concluded that both FIB-4 and APRI showed only fair or modest discrimination in this cohort, with enough misclassification risk to limit standalone staging claims.

Clinician Questions

What VCTE cutoff defined significant fibrosis in adults with chronic hepatitis B in this cohort?

In 247 adults with chronic hepatitis B, significant fibrosis was defined as VCTE at or above 7.25 kPa; advanced fibrosis was defined at or above 9.3 kPa, and cirrhosis was defined at or above 12.4 kPa.

How did FIB-4 compare with APRI for detecting significant fibrosis in chronic hepatitis B?

In adults with chronic hepatitis B, investigators found that FIB-4 performed slightly better than APRI for detecting VCTE-defined significant fibrosis, with AUROC 0.686 versus 0.660; at cut points above 0.88 for FIB-4 and above 0.32 for APRI, sensitivity was 65.42% versus 63.55% and specificity was 60.0% for both scores.

Which findings remained independently associated with significant fibrosis in the chronic hepatitis B cohort?

In the chronic hepatitis B cohort, FIB-4 remained associated with significant fibrosis in multivariable analysis with OR 1.558 (95% CI 1.203-2.017; P=0.001), whereas hemoglobin, albumin, and INR did not remain significant after adjustment.

What patient groups were compared in the chronic hepatitis B fibrosis accuracy analysis?

The analysis included 247 adults with chronic hepatitis B, grouped by VCTE into 140 patients with F0-F1 fibrosis and 107 with F2-F4 significant fibrosis; within the significant-fibrosis group, 38 were F2, 14 were F3, and 55 were F4, and the study excluded HCV or HIV coinfection, blood malignancies, and decompensated cirrhosis.