Stratification of hepatocellular carcinoma risk through modified FIB-4 index in chronic hepatitis B patients on entecavir therapy

Abstract

Background and aim: Noninvasive fibrosis indices can predict the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). Modified FIB-4 (mFIB-4) is a promising noninvasive index for predicting liver fibrosis. To investigate the predictive accuracy of several extant noninvasive fibrosis indices, including mFIB-4, for HCC incidence in CHB patients receiving long-term entecavir therapy.

Methods: We enrolled 1325 nucleos(t)ide analogue-naïve CHB patients (noncirrhotic 844; cirrhotic 481) treated with entecavir. Baseline clinical features and fibrosis indices were collected and evaluated for predicting HCC risk through univariate and multivariate Cox regression analyses.

Results: Of the 1325 patients, 105 (7.9%) developed HCC during a median follow-up period of 4.1 years. Age (hazard ratio [HR], 1.039; 95% confidence interval [CI], 1.020-1.059; P < 0.0001), diabetes mellitus (DM) (HR, 1.902; 95% CI, 1.185-3.052; P = 0.0077), and mFIB-4 (HR, 4.619; 95% CI, 1.810-11.789; P = 0.0014) were independent predictors of HCC in all patients (mFIB-4 ≥ 1.5 for the noncirrhotic cohort; DM and mFIB-4 ≥ 2.0 for the cirrhotic cohort). A combination of mFIB-4 and the DM status stratified the cumulative risk of HCC into three subgroups in all patients (high: mFIB-4 ≥ 1.5/DM; intermediate: mFIB-4 ≥ 1.5/non-DM; and low: mFIB-4 < 1.5, P < 0.0001) and in the cirrhotic cohort (high: mFIB-4 ≥ 2.0/DM; intermediate: mFIB-4 ≥ 2.0/non-DM; and low: mFIB-4 < 2.0, P = 0.0007). An mFIB-4 cutoff value of 1.5 stratified the cumulative risk of HCC in the noncirrhotic cohort (P = 0.015).

Conclusions: The mFIB-4 index alone or in combination with DM is the optimal noninvasive predictor of HCC risk in CHB patients receiving entecavir therapy.

Keywords: chronic hepatitis B; entecavir; hepatocellular carcinoma; modified FIB-4 (mFIB-4); noninvasive fibrosis index.