A combination of the on-treatment FIB-4 and alpha-foetoprotein predicts clinical outcomes in cirrhotic patients receiving entecavir.

Background & Aims: This study investigates the long-term incidences and predictors of developing hepatocellular carcinoma (HCC), cirrhotic events and mortality in cirrhotic patients receiving entecavir (ETV) therapy.

Methods: We enrolled 481 nucleos(t)ide analogue-naïve chronic hepatitis B (CHB) patients who had compensated cirrhosis upon entry and had received ETV monotherapy for >12 months.

Results: The 8-year cumulative incidences of developing HCC, cirrhotic events and liver-related mortality were 26.5%, 8.62% and 10.03% respectively. Multivariate analysis revealed that diabetic mellitus (DM), higher fibrosis-4 (FIB-4) and alpha-foetoprotein (AFP) levels at 12 months of treatment, and FIB-4 increase from baseline to 12 months were independent factors of HCC. FIB-4 and AFP levels at 12 months of treatment were also independent factors of cirrhotic events and mortality. FIB-4 cut-off values of 3, 3 and 5 as well as AFP cut-offs of 5, 5, and 9 ng/mL at 12 months of treatment were optimal for predicting HCC, cirrhotic events and mortality during therapy respectively. The FIB-4 and AFP levels at 12 months of treatment were assessed for the combined risk of developing clinical outcomes. The 8-year incidences of HCC, cirrhotic events and liver-related mortality in the subgroups with low FIB-4 and AFP levels were only 5.95%, 1.03% and 2.43% respectively. DM was an independent predictor of HCC and mortality.

Conclusion: The combination of FIB-4 and AFP levels at 12 months of treatment is a useful marker for predicting the development of HCC, cirrhotic events and mortality in compensated cirrhotic patients with CHB who are receiving ETV therapy.