ORIGINAL CONTRIBUTION Risk of Hepatocellular Carcinoma Across a Biological Gradient of Serum Hepatitis B Virus DNA Level

MORE THAN 350 MILLIONpersons in the world areinfected with chronichepatitis B virus (HBV).1 It is particularly endemic in Taiwan, where the infection is usually ac-quired perinatally or in early child-hood.2 Individuals with chronic hepa-titis B infection are at an increased risk of developing liver cirrhosis, hepatic de-compensation, and hepatocellular car-cinoma3; 15 % to 40 % of these individu-als will develop these serious sequelae during their lifetime.3,4 Hepatitis B vi-rus is not directly cytopathic, and the development of hepatocellular carci-noma in individuals with chronic hepa-titis B is a multistage, multifactorial pro-cess including the interaction between host and environmental factors.5 Risk factors for chronic HBV-related hepa-tocellular carcinoma include sex, age, cigarette smoking, alcohol consump-tion, chemical carcinogens, hormonal factors, and genetic susceptibility.6 Seropositivity for the hepatitis B surface antigen (HBsAg) is one of the most important risk factors for hepa-tocellular carcinoma.6 The risk of he-patocellular carcinoma associated with seropositivity for HBsAg ranges from 5-fold to 98-fold with a population-attributable risk of 8 % to 94%.6 In our previous study, seropositivity for the hepatitis B e antigen (HBeAg) wa