The Correlation of Hepatocellular Carcinoma and Different Hepatitis B Virus Genotypes with Spontaneous YMDD Mutation_West China Medical Journal

Authors：

 CHENXue-bing ,  YANGJia-hong , ZHANGHao , CHENGao , WANGXiu , LUOWan-rong

Department of Infectious Diseases, People's Hospital of Deyang City, Deyang, Sichuan 618000, P. R. China;

Corresponding author：

YANGJia-hong, Email: 18990283956@163.com

Keywords：

Hepatitis B virus; Hepatitis B virus-related hepatocellular carcinoma; Genotype; YMDD mutation

DOI：

10.7507/1002-0179.20150471

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the correlation of spontaneous YMDD mutation in different hepatitis B virus (HBV) genotypes with HBV-related hepatocellular carcinoma (HCC). Method From May 2010 to May 2012, 110 HBV-related hepatocellular cancer patients not treated by anti-virus drugs and 1 079 chronic HBV infectors (including asymptomatic HBV carriers, chronic hepatitis B patients, and HBV-related liver cirrhosis patients) were included in our study. HBV YMDD mutation was detected by fluorescence hybridization bioprobe polymerase chain reaction (PCR) and melting curve assay using Diagnosis Kit for HBV YMDD Mutation (Qiagen Biotechnology). Serum HBV genotype was detected by real time PCR using genotype specific TaqMan probe. According to data type, t-test, χ²-test and unconditional logistic regression were used for statistical analysis. Results In the HCC group, genotype C virus, spontaneous YMDD mutation and genotype C virus with YMDD mutation were detected in 39 patients (35.5%), 16 patients (14.5%) and 14 patients (12.7%), respectively. In the chronic HBV infection group, HBV genotype C virus, spontaneous YMDD mutation and genotype C virus with YMDD mutation were detected in 153 patients (14.2%), 46 patients (4.3%) and 17 patients (1.6%), respectively. The difference between the two groups were statistically significant (χ²=33.368, P<0.001; χ²=21.353, P<0.001; χ²=48.889, P<0.001). Unconditional logistic regression analysis suggested that infection of genotype C virus and genotype C virus with spontaneous YMDD mutation might be important risk factors for the development of HCC[OR=2.943, 95%CI (1.778, 4.872), P<0.001; OR=5.989, 95%CI (2.394, 14.980), P<0.001]. Conclusions Infection of genotype C virus with spontaneous YMDD mutation is tightly related with the occurrence of HCC and has important value for earlier warning of HCC.

Citation： CHENXue-bing, YANGJia-hong, ZHANGHao, CHENGao, WANGXiu, LUOWan-rong. The Correlation of Hepatocellular Carcinoma and Different Hepatitis B Virus Genotypes with Spontaneous YMDD Mutation. West China Medical Journal, 2015, 30(9): 1650-1653. doi: 10.7507/1002-0179.20150471 Copy

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18.	Wong GL, Chan HL, Yiu KK, et al. Meta-analysis:The association of hepatitis B virus genotypes and hepatocellular carcinoma[J]. Aliment Pharmacol Ther, 2013, 37(5):517-526.
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1. Alter MJ. Epidemiology of hepatitis B in Europe and worldwide[J]. J Hepatol, 2003, 39(Suppl 1):S64-S69.
2. Custer B, Sullivan SD, Hazlet TK, et al. Global epidemiology of hepatitis B virus[J]. J Clin Gastroenterol, 2004, 38(10, S):S158-S168.
3. Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures[J]. J Viral Hepat, 2004, 11(2):97-107.
4. Liang X, Bi S, Yang W, et al. Epidemiological serosurvey of hepatitis B in China——declining HBV prevalence due to hepatitis B vaccination[J]. Vaccine, 2009, 27(47):6550-6557.
5. Liang X, Bi S, Yang W, et al. Evaluation of the impact of hepatitis B vaccination among children born during 1992-2005 in China[J]. J Infect Dis, 2009, 200(1):39-47.
6. Lu FM, Zhuang H. Management of hepatitis B in China[J]. Chin Med J (Engl), 2009, 122(1):3-4.
7. Lee WM. Hepatitis B virus infection[J]. N Engl J Med, 1997, 337(24):1733-1745.
8. Liu C, Wang YM, Fan K. Epidemiological and clinical features of hepatitis B virus related liver failure in China[J]. World J Gastroenterol, 2011, 17(25):3054-3059.
9. Tan YJ. Hepatitis B virus infection and the risk of hepatocellular carcinoma[J]. World J Gastroenterol, 2011, 17(44):4853-4857.
10. Moskovitz DN, Osiowy C, Giles E, et al. Response to long-term lamivudine treatment (up to 5 years) in patients with severe chronic hepatitis B, role of genotype and drug resistance[J]. J Viral Hepat, 2005, 12(4):398-404.
11. Yıldız O, Aygen B, Demirtürk N, et al. Lamivudine resistance mutations in patients infected with hepatitis B virus genotype D[J]. World J Gastroenterol, 2011, 17(45):4987-4992.
12. Kobayashi S, Ide T, Sata M. Detection of YMDD motif mutations in some lamivudine-untreated asymptomatic hepatitis B virus carriers[J]. J Hepatol, 2001, 34(4):584-586.
13. Ming XC, Miao XH, Zhao SM, et al. The spontaneous YMDD mutation rate in chronic hepatitis B patient[J]. Chin J Hepatol, 2009, 17(12):887-890.
14. Shin YM, Heo J, Kim GH, et al. Natural YMDD motif mutations of HBV polymerase in the chronic hepatitis B virus infected patients[J]. Taehan Kan Hakhoe Chi, 2003, 9(1):1-9.
15. Chan HL, Hui AY, Wong ML, et al. Genotype C hepatitis B virus infection is associated with an increased risk of hepatocellular carcinoma[J]. Gut, 2004, 53(10):1494-1498.
16. Kao JH, Chen PJ, Lai MY, et al. Hepatitis B genotypes correlate with clinical outcomes in patients with chronic hepatitis B[J]. Gastroenterology, 2000, 118(3):554-559.
17. Orito E, Ichida T, Sakugawa H, et al. Geographic distribution of hepatitis B virus (HBV) genotype in patients with chronic HBV infection in Japan[J]. Hepatology, 2001, 34(3):590-594.
18. Wong GL, Chan HL, Yiu KK, et al. Meta-analysis:The association of hepatitis B virus genotypes and hepatocellular carcinoma[J]. Aliment Pharmacol Ther, 2013, 37(5):517-526.
19. 中华人民共和国卫生部. 原发性肝癌诊疗规范(2011年版)[J]. 临床肝胆病杂志, 2011, 27(11):1141-1159.
20. 中华医学会传染病与寄生虫病学分会, 中华医学会肝病学分会. 病毒性肝炎防治方案[J]. 中华肝脏病杂志, 2000, 8(6):324-329.
21. Hosaka T, Suzuki F, Kobayashi M, et al. Development of HCC in patients receiving adefovir dipivoxil for lamivudine-resistant hepatitis B virus mutants[J]. Hepatol Res, 2010, 40(2):145-152.
22. Ohkubo K, Kato Y, Ichikawa T, et al. Viral load is a significant prognostic factor for hepatitis B virus-associated hepatocellular carcinoma[J]. Cancer, 2002, 94(10):2663-2668.

West China Medical Journal

The Correlation of Hepatocellular Carcinoma and Different Hepatitis B Virus Genotypes with Spontaneous YMDD Mutation

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