Using data from large-scale surveys of HCC incidence and viral hepatitis prevalence, we calculated the incidence of HBV-related HCC in the two countries [2]. In total, 798,125 Korean people (40 to 79 years of age) were hepatitis B surface antigen (HBsAg)-positive in 2005, and 10,456 HCCs were recorded in the same age group. Among them, 7,560 (72.3%) were HBV-related HCCs. The annual incidence of HCC was 947 per 100,000 persons with HBV infection (Fig. 1). This was equivalent to one HCC occurrence for every 106 persons with HBV infection per year. From 2005 to 2011, the annual incidence of HBV-related HCC in Korea did not change; the average incidence was 906 per 100,000 persons with HBV infection (0.91%/year). In Taiwan, 1,096,944 persons (40 to 79 years of age) were HBsAg-positive in 2002, and 6,390 new HCC cases were reported in the same age group. Among them, 4,147 (64.9%) were HBV-related HCCs. The annual incidence was 378 per 100,000 persons with HBV infection in Taiwan (Supplementary Table 1) [3-15].

Because different demographic characteristics and HCC detection rate might affect incidence of HBV-related HCC, we confined our analysis to young age group (40 to 49 years). Not only incidence but mortality from HBV-related HCC was investigated. The incidence was 495 and 155 per 100,000 persons with HBV infection in Korea and Taiwan, respectively. The mortality was also largely different, 434 and 136 per 100,000 persons with HBV infection in Korea and Taiwan, respectively.

This marked difference in HCC incidence prompted us to conduct an identical analysis among hepatitis C virus (HCV)-positive patients (Supplementary Table 2) [2,10-12,14,16-18]. Population data, prevalence of chronic hepatitis C, and annual number of HCV-related HCC cases (40 to 79 years of age) were acquired from publicly available data. Interestingly, the annual incidence of HCV-related HCC was similar in the two countries: 570 and 519 per 100,000 persons with HCV infection in Korea and Taiwan, respectively (Fig. 1). Based on this finding, we postulate that viral factors, rather than host or environmental factors, may play a major role in the marked difference in development of HBV-related HCC between the two countries.

The majority of Asians infected with HBV have genotype B or C virus, which is associated with vertical transmission. Korea is a racially homogenous country in which all HBVs are genotype C, whereas genotype B is the most prevalent in Taiwan [19]. Genotype C HBV is associated with higher serum viral load, delayed hepatitis B e antigen seroconversion, and a higher risk of disease progression to liver cirrhosis or HCC than those of the other genotypes [20,21]. Although unknown host or environmental factors may exist, viral factors, particularly genotype C virus, might have a critical role in HCC development among Korean patients.