Effectiveness of entecavir in preventing hepatocellular carcinoma development is genotype-dependent in hepatitis B virus-associated liver cirrhosis

BACKGROUND: The oral nucleos(t)ide analogue, entecavir (ETV) was demonstrated to reduce the rate of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV)-associated liver cirrhosis. However, the reduction of HCC differs in various regions of the world. AIM: To investigate the reduction of HCC development due to ETV therapy by meta-analysis. METHODS: We surveyed the differences in HCC development following ETV treatment based on published articles using PubMed (2004-2019). RESULTS: The regions with the most marked reduction in HCC development due to ETV therapy were Spain (1.0%/year) and Canada (Southern part, 1.3%/year), and the most ineffective areas were South Korea (3.6%-3.8%/year), China (3.3%/year), Taiwan (2.4%-3.1%/year), and Hong Kong (2.8%/year). Following ETV administration, the incidence of HCC in genotype D regions (1.89% ± 0.28%/year, mean ± SE) was significantly lower than that in genotype C regions (2.91% ± 0.24%/year, P < 0.01). With regard to the initial HBV-DNA level, in genotype C patients (average: 5.61 Log(10)IU/mL) this was almost the same as that in genotype D patients (average: 5.46 Log(10)IU/mL). Moreover, there was no association between the prevalence ratio of HBV and the incidence of HCC on ETV treatment. CONCLUSION: The effectiveness of ETV in preventing HCC development in HBV-associated liver cirrhosis is genotype-dependent.