Effect of Virological Response to Entecavir on the Development of Hepatocellular Carcinoma in Hepatitis B Viral Cirrhotic Patients: Comparison Between Compensated and Decompensated Cirrhosis

OBJECTIVES: This study aimed to evaluate the risk of development of hepatocellular carcinoma (HCC) according to underlying liver status and virological response (VR) to entecavir (ETV) in chronic hepatitis B patients with cirrhosis. Procollagen III N-terminal peptide (PIIINP) concentration during ETV treatment and its association with HCC development were also evaluated. METHODS: A total of 306 patients with clinically diagnosed liver cirrhosis were treated with ETV for >= 12 months and were subsequently followed up for the occurrence of HCC (median follow-up duration: 37.0 months). Patients who developed HCC within 12 months were excluded. VR was defined as a hepatitis B virus DNA level < 20 IU/ml at 12 months after ETV treatment. RESULTS: A total of 209 patients (68.3%) had compensated cirrhosis, and the remaining patients (31.7%) had decompensated cirrhosis. The 5-year cumulative incidence of HCC was 26.8%. A multivariate Cox regression analysis identified the following independent risk factors for developing HCC in all the patients: age > 50 years (hazard ratio (HR) = 8.41; 95% confidence interval (CI) = 3.86-18.28; P = 0.000), male sex (HR = 4.24; 95% CI = 1.83-9.81; P = 0.001), high serum PIIINP level at 12 months (HR = 1.07; 95% CI = 1.02-1.13; P = 0.007), and no VR at 12 months (HR = 2.10; 95% CI = 1.02-4.33; P = 0.043). The subgroup analyses showed that no VR at 12 months is a significant risk factor for developing HCC in the patients with decompensated cirrhosis (HR = 7.74; 95% CI = 1.34-44.78; P = 0.022) but not in those with compensated cirrhosis (P = 0.749). CONCLUSIONS: The antiviral treatment with ETV did not completely eliminate the risk of developing HCC in our patients with cirrhosis. However, VR to ETV was associated with a low probability that the patients with decompensated cirrhosis would develop HCC.