BACKGROUND AND

AIMS: Fibrosis-4 (FIB-4) index is a HCC predictor in chronic hepatitis B (CHB) patients . However, little is known about whether FIB-4 helps identify non-cirrhotic CHB patients with minimal HCC risk after prolonged nucleos (t) ide analogue (NA) therapy .

METHODS: A total of 1936 ethnically diverse, non-cirrhotic CHB patients were enrolled in this retrospective multi-national study . All patients received prolonged NA treatment, including entecavir and tenofovir disoproxil fumarate . We explored whether FIB-4 cutoff of 1.30, a marker indicative of mild fibrosis severity, could stratify HCC risks in these patients .

RESULTS: A total of 48 patients developed HCC after a mean follow-up of 6.98 years . FIB-4 level at 1 year after treatment (1-year FIB-4) was shown to be associated with HCC development and was superior to pre-treatment FIB-4 value . When patients were stratified by 1-year FIB-4 of 1.30, the high FIB-4 group was at an increased HCC risk compared to the low FIB-4 group, with a hazard ratio of 4.87 (95% confidence interval : 2.48-9.55). Multivariable analysis showed that sex and 1-year FIB-4 were independent predictors, with none of the 314 female patients with low 1-year FIB-4 developing HCC . Finally, 1-year FIB-4 of 1.30 consistently stratified HCC risks in patients with low PAGE-B score, a score composed of baseline age, sex and platelet count, and the annual incidence rate of HCC was 0.11% in those with PAGE-B <10 + 1-year FIB-4 <1.30 .

CONCLUSIONS: In non-cirrhotic CHB patients receiving prolonged NA therapy, 1-year FIB-4 <1.30 is useful for identifying those with minimal HCC risk by combining with female sex or low PAGE-B score.