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

Abstract

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. 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. Of the 1325 patients, 105 (7.9%) developed HCC during a median follow-up period of 4.1years. 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). The mFIB-4 index alone or in combination with DM is the optimal noninvasive predictor of HCC risk in CHB patients receiving entecavir therapy.