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 metaanalysis.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 Log10IU/mL)this was almost the same as that in genotype D patients(average:5.46 Log10IU/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.