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Carcinogenesis Advance Access originally published online on January 12, 2008
Carcinogenesis 2008 29(9):1685-1691; doi:10.1093/carcin/bgm301
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Role of hepatitis B virus genotype mixture, subgenotypes C2 and B2 on hepatocellular carcinoma: compared with chronic hepatitis B and asymptomatic carrier state in the same area

Jianhua Yin, Hongwei Zhang, Chengzhong Li1, Chunfang Gao2, Yongchao He, Yujia Zhai, Peng Zhang, Ling Xu, Xiaojie Tan, Jinsong Chen, Shuqun Cheng3, Stephan Schaefer4 and Guangwen Cao*

Department of Epidemiology
1 Department of Infectious Diseases, Changhai Hospital
2 Department of Experimental Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, People’s Republic of China
3 Department of Comprehensive Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, People’s Republic of China
4 Abteilung für Virologie, Universität Rostock, Germany

* To whom correspondence should be addressed. Email: gcao{at}smmu.edu.cn

The role of genotype mixture and subgenotypes remains controversial in determining the clinical outcome of chronic hepatitis B virus (HBV) infection. We aimed to determine their role on the development and the recurrence of hepatocellular carcinoma (HCC). HBV genotypes, serum viral load and hepatitis B e antigen (HBeAg) seroconversion were determined in 462 HCC patients, 234 chronic hepatitis patients and 425 asymptomatic carriers born in Eastern China. In the 462 HCC patients, 62 (13.4%), 337 (72.9%) and 49 (10.6%) had HBV subgenotype B2, C2 and genotype mixture, respectively. Genotype mixture in HCC patients and hepatitis patients was associated with higher viral load than HBV C2 (P = 0.012, P = 0.000) and more frequent than asymptomatic carriers (P = 0.005, P = 0.000). HBV C2 was more prevalent in HCC patients compared with controls. Proportion of HBV B2 in HCC patients decreased consecutively from <30 to 50–59 years group (P = 0.024). Age-related changes of HBeAg seroconversion were not consistent with serum viral load in HCC patients with HBV B2 and genotype mixture, quite in contrast to hepatitis patients. By multivariate regression analysis, age ≥40 years and serum viral load (≥10 000 copies/ml) were independently associated with hepatocarcinogenesis, whereas age ≤50 years and HBV B2 were independently associated with HCC recurrence after surgical resection. In conclusion, HBV coinfections with two or three genotypes were associated with higher viral load and more severe course of the disease. HBV B2 infection was related to HCC recurrence. HBV C2 predominance in HCC patients was related to the high prevalence in Eastern China.

Abbreviations: AFP, alpha-fetoprotein; AntiHBe, antibody to hepatitis B e antigen; ASC, asymptomic HBsAg carrier; CH, chronic hepatitis B; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCC, hepatocellular carcinoma

Received October 3, 2007; revised November 23, 2007; accepted December 22, 2007.


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