Hepatocellular carcinoma (HCC) caused by chronic hepatitis B virus (HBV) infection is a major health problem in Asian people [1]. We herein report an interesting finding that large difference exists even between two Asian countries in terms of HBV-related HCC occurrence. We found that incidence of HBV-related HCCs is more than twice in Koreans than in Taiwanese in spite of similar risk factors between two countries.
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].
Figure 1.

Annual incidence of hepatocellular carcinoma (HCC) in patients with chronic viral hepatitis B or C. Data were obtained from national cancer reports and large-scale prevalence studies of viral hepatitis in Korea and Taiwan. The annual incidence of hepatitis B virus (HBV) (or hepatitis C virus [HCV]) -related HCC per 100,000 persons with HBV (or HCV) infection is shown.
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.
Footnotes
No potential conflict of interest relevant to this article was reported.
Supplementary Materials
Annual incidence of HBV-related HCC among HBsAg positive persons in Korea and Taiwan
Annual incidence of HCV-related HCC among HCV-positive persons in Korea and Taiwan
REFERENCES
- 1.El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557–2576. doi: 10.1053/j.gastro.2007.04.061. [DOI] [PubMed] [Google Scholar]
- 2.de Martel C, Maucort-Boulch D, Plummer M, Franceschi S. World-wide relative contribution of hepatitis B and C viruses in hepatocellular carcinoma. Hepatology. 2015;62:1190–1200. doi: 10.1002/hep.27969. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Ministry for Health, Welfare and Family Affairs . Seoul (KR): Ministry for Health, Welfare and Family Affairs; 2008. Annual report of cancer incidence (2005) and survival (1993-2005) in Korea [Internet] [cited 2017 Jun 28]. Available from: http://ncc.re.kr/cancerStatsList.ncc?-searchKey=total&searchValue=&pageNum=1. [Google Scholar]
- 4.Ministry for Health, Welfare and Family Affairs . Seoul (KR): Ministry for Health, Welfare and Family Affairs; 2009. Annual report of cancer incidence (2007), cancer prevalence (2007) and survival (1993-2007) in Korea [Internet] [cited 2017 Jun 28]. Available from: http://ncc.re.kr/cancerStatsList.ncc?searchKey=total&searchValue=&pageNum=1. [Google Scholar]
- 5.Ministry of Health and Welfare. Korea Central Cancer Registry. National Cancer Center . Goyang (KR): National Cancer Center; 2010. Annual report of cancer statistics in Korea in 2008 [Internet] [cited 2017 Jun 28]. Available from: http://ncc.re.kr/cancerStatsView.ncc?bbsnum=189&-searchKey=total&searchValue=&pageNum=2. [Google Scholar]
- 6.Ministry of Health and Welfare. Korea Central Cancer Registry. National Cancer Center . Goyang (KR): National Cancer Center; 2011. Annual report of cancer statistics in Korea in 2009 [Internet] [cited 2017 Jun 28]. Available from: http://ncc.re.kr/cancerStatsView.ncc?bbsnum=229&-searchKey=total&searchValue=&pageNum=2. [Google Scholar]
- 7.Ministry of Health and Welfare. Korea Central Cancer Registry. National Cancer Center . Goyang (KR): National Cancer Center; 2012. Annual report of cancer statistics in Korea in 2010 [Internet] [cited 2017 Jun 28]. Available from: http://ncc.re.kr/cancerStatsView.ncc?bbsnum=250&-searchKey=total&searchValue=&pageNum=1. [Google Scholar]
- 8.Ministry of Health and Welfare. Korea Central Cancer Registry. National Cancer Center . Goyang (KR): National Cancer Center; 2013. Annual report of cancer statistics in Korea in 2011 [Internet] [cited 2017 Jun 28]. Available from: http://ncc.re.kr/cancerStatsView.ncc?bbsnum=295&-searchKey=total&searchValue=&pageNum=1. [Google Scholar]
- 9.Kim H, Shin AR, Chung HH, et al. Recent trends in hepatitis B virus infection in the general Korean population. Korean J Intern Med. 2013;28:413–419. doi: 10.3904/kjim.2013.28.4.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Park JW, Kim CM. Epidemiology of hepatocellular carcinoma in Korea. Korean J Hepatol. 2005;11:303–310. [PubMed] [Google Scholar]
- 11.Kim KS, Kim SH, Kim IH, et al. Report of Primary Liver Cancer Randomised Registration in Korea. Seoul (KR): The Korean Liver Cancer Study Group, National Cancer Registration Center; 2010. [Google Scholar]
- 12.National Statistics Republic of China (Taiwan) Taipei City (TW): National Statistics Republic of China (Taiwan); Statistical yearbook of the Republic of China 2014 [Internet] [cited 2017 Jun 28]. Available from: http://eng.stat.gov.tw/lp.asp?ctNode=2265&CtUnit=1072&BaseDSD=36. [Google Scholar]
- 13.Chen CL, Yang JY, Lin SF, et al. Slow decline of hepatitis B burden in general population: results from a population-based survey and longitudinal follow-up study in Taiwan. J Hepatol. 2015;63:354–363. doi: 10.1016/j.jhep.2015.03.013. [DOI] [PubMed] [Google Scholar]
- 14.Health Promotion Administration, Ministry of Health and Welfare. Cancer Registry Annual Report (2002) Taipei City (TW): Ministry of Health and Welfare; 2006. [Google Scholar]
- 15.Chen CH, Su WW, Yang SS, et al. Long-term trends and geographic variations in the survival of patients with hepatocellular carcinoma: analysis of 11,312 patients in Taiwan. J Gastroenterol Hepatol. 2006;21:1561–1566. doi: 10.1111/j.1440-1746.2006.04425.x. [DOI] [PubMed] [Google Scholar]
- 16.Ministry of Health and Welfare. Korea Central Cancer Registry. National Cancer Center . Goyang (KR): National Cancer Center; 2014. Annual report of cancer statistics in Korea in 2012 [Internet] [cited 2017 Jun 28]. Available from: http://ncc.re.kr/cancerStatsView.ncc?bbsnum=316&-searchKey=total&searchValue=&pageNum=1. [Google Scholar]
- 17.Korea Centers for Disease Control and Prevention . Cheongju (KR): Korea Centers for Disease Control and Prevention; c2012. The fifth Korea National Health and Nutrition Examination Survey (KNHANES V-3), 2012 [Internet] [cited 2017 Jun 28]. Available from: http://cdc.go.kr/CDC/contents/CdcKrContentView.jsp?cid=60939&menuIds=HOME001-MNU1130-MNU1639-MNU1748-MNU1751. [Google Scholar]
- 18.Chen CH, Yang PM, Huang GT, Lee HS, Sung JL, Sheu JC. Estimation of seroprevalence of hepatitis B virus and hepatitis C virus in Taiwan from a large-scale survey of free hepatitis screening participants. J Formos Med Assoc. 2007;106:148–155. doi: 10.1016/S0929-6646(09)60231-X. [DOI] [PubMed] [Google Scholar]
- 19.Sunbul M. Hepatitis B virus genotypes: global distribution and clinical importance. World J Gastroenterol. 2014;20:5427–5434. doi: 10.3748/wjg.v20.i18.5427. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Livingston SE, Simonetti JP, Bulkow LR, et al. Clearance of hepatitis B e antigen in patients with chronic hepatitis B and genotypes A, B, C, D, and F. Gastroenterology. 2007;133:1452–1457. doi: 10.1053/j.gastro.2007.08.010. [DOI] [PubMed] [Google Scholar]
- 21.Wong GL, Chan HL, Yiu KK, et al. Meta-analysis: the association of hepatitis B virus genotypes and hepatocellular carcinoma. Aliment Pharmacol Ther. 2013;37:517–526. doi: 10.1111/apt.12207. [DOI] [PubMed] [Google Scholar]
Associated Data
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Supplementary Materials
Annual incidence of HBV-related HCC among HBsAg positive persons in Korea and Taiwan
Annual incidence of HCV-related HCC among HCV-positive persons in Korea and Taiwan
