Correlation of Primary Hepatocellular Carcinoma with HBV Genotypes, Subgenotypes and Gene Mutations in Gansu Province

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Objective To investigate the occurrence of basal core promoter (BCP) and pre-C mutations in patients with hepatitis B virus (HBV) infection in Gansu Province, China, and to analyze the correlation of HBV mutation and HBV genotype with primary hepatocellular carcinoma (HCC).

Methods PCR-RFLP was applied to detect HBV subgenotypes, and the presence of the pre-C and BCP mutations in 62 patients with HCC, 70 patients with hepatitis B induced liver cirrhosis (LC) and 90 patients with chronic hepatitis B (CHB).

Results In HCC patients, genotype C was the major genotype (70.97%). The pre-C mutation was found in 59.68%, 31.43% and 16.67% patients with HCC, LC and CHB, respectively. The frequency of BCP mutations was significantly different between patients with HCC, LC and CHB (74.19%, 51.43% and 37.78%, respectively; X2=30.727, 19.540, respectively, P < 0.01). Patients in HCC group had a higher incidence of pre-C as well as BCP mutations compared to the other groups. The prevalence of pre-C and BCP mutations was significantly higher in patients with genotype C1 (44.32% and 69.32%, respectively) compared to patients with other subgenotypes (P < 0.05).

Conclusions The incidence of pre-C and BCP mutations increases with disease progression. Pre-C and BCP mutations frequently occur in patients with genotype C1. HBV genotype C, pre-C mutations and BCP mutations are closely related to the occurrence of HCC.

1. Chinese Society of Hepatology. Guideline for Prevention and Treatment of Viral Hepatitis. Zhonghua Chuan Ran Bing Za Zhi (Chin) 2001;19(L):56-62.

2. Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology 2005; 42(5):1208-1236.

3. Zeng GB, Wen SJ, Wang ZH, Yan L, Sun J, Hou JL. A novel hepatitis B virus genotyping system by using restriction fragment length polymorphism patterns of S gene amplicons. World J Gastroenterol 2004; 10(21):3132-3136.

4. Tanaka Y, Orito E, Yuen MF, Mukaide M, Sugauchi F, Ito K, et al. Two subtypes (subgenotypes) of hepatitis B virus genotype C: A novel subtyping assay based on restriction fragment length polymorphism. Hepatol Res 2005; 33(3):216-224.

5. Sugauchi F, Kumada H, Sakugawa H, Komatsu M, Niitsuma H, Watanabe H, et al. Two subtypes of genotype B (Ba and Bj) of hepatitis B virus in Japan. Clin Infect Dis 2004; 38(9):1222-1228.

6. Hou J, Lau GK, Cheng J, Cheng CC, Luo K, Carman WF. T1762/A1764 variants of the basal core promoter of hepatitis B virus; serologieal and clinical correlations in Chinese patients. Liver 1999; 19(5):411-417.

7. Sugiyama M, Mizokami M. Hepatitis B virus genotype and the mutation related to clinical outcome. Nihon Rinsho 2011; 69(4):350-355.

8. Shi YH. Correlation between hepatitis B virus genotypes and clinical outcomes. Jpn J Infect Dis 2012; 65(6):476-482.

9. Chen Y, Yu D, Zhang W, Qiu C, Xiang G, Dai W, et al. HBV subgenotype C2 infection, A1762T/G1764A mutations may contribute to hepatocellular carcinoma with cirrhosis in southeast China. Iran J Public Health 2012; 41(11):10-18.

10. Yuen MF, Sablon E, Yuan HJ, Wong DK, Hui CK, Wong BC, et al. Significance of hepatitis B genotype in acute exacerbation, HBeAg seroconversion, cirrhosis-related complications,and hepatocellular carcinoma. Hepatology 2003; 37(3):562-567.

11. Chan HL, Hui AY, Wong ML, Tse AM, Hung LC, Wong VW, et al. Genotype C hepatitis B virus infection is associated with an increased risk of hepatocellular carcinoma. Gut 2004; 53 (10):1494-1498.

12. Kao JH. Hepatitis B virus genotypes and hepatocellular carcinoma in Taiwan. Intervirology 2003; 46(6):400-407.

13. Kao JH, Chen PJ, Lai MY, Chen DS. Genotypes and clinical phenotypes of hepatitis B virus in patients with chronic hepatitis B virus infection. J Clin Microbiol 2002; 40 (4):1207-1209.

14. Zhou B, Huang YH, Shan GH, Hou JL, Wang ZH, Wen SJ. Influences of HBV genotype and mutations on progression of liver disease. J Trop Med 2008; 8(4):302-305.

15. Yuen MF, Tanaka Y, Mizokami M, Yuen JC, Wong DK, Yuan HJ, et al. Role of hepatitis B virus genotypes Ba and C, core promoter and precore mutations on hepatocellular carcinoma: a case control study. Carcinogenesis 2004; 25(9):1593-1598.

16. Liu CJ, Chen BF, Chen PJ, Lai MY, Huang WL, Kao JH, et al. Role of hepatitis B viral load and basal core promoter mutation in hepatocellular carcinoma in hepatitis B carriers. J Infect Dis 2006; 193(9):1258 -1265.

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