乙型肝炎病毒基因型与自发 YMDD 突变与肝细胞癌的关系。
Relationship between hepatocellular carcinoma and hepatitis B virus genotype with spontaneous YMDD mutations.
机构信息
Department of Infectious Diseases, People's Hospital of Deyang City, Deyang 618000, Sichuan Province, China.
出版信息
World J Gastroenterol. 2013 Jun 28;19(24):3861-5. doi: 10.3748/wjg.v19.i24.3861.
AIM
To investigate the relationship between hepatitis B virus (HBV) genotype with spontaneous YMDD mutations and hepatocellular carcinoma (HCC) in HBV-related cirrhosis.
METHODS
We investigated 264 liver cirrhosis patients who were not treated with antiviral drugs, including 81 patients with HCC. YMDD mutations were detected by fluorescent hybridization bioprobe polymerase chain reaction (PCR) and melting curve assay using the Diagnosis Kit for HBV YMDD Mutation. Serum HBV genotypes were detected by real-time PCR using genotype-specific TaqMan probes. Statistical analysis was performed according to data type using the t test, χ(2) test and unconditional logistic regression analysis.
RESULTS
In the HCC group, genotype C strains, spontaneous YMDD mutations, and genotype C strains with YMDD mutations were detected in 33 (40.74%), 13 (16.05%) and 11 (13.58%) patients, respectively. In the liver cirrhosis (LC) group, HBV genotype C strains, spontaneous YMDD mutations, and genotype C strains with YMDD mutations were detected in 33 (18.03%), 7 (3.83%) and 2 (1.09%) patients, respectively. The differences in genotype C strains, spontaneous YMDD mutations, and genotype C strains with YMDD mutations between the two groups were statistically significant (χ(2) = 15.441, P = 0.000; χ(2) = 11.983, P = 0.001; P = 0.000). In the HCC and LC groups, there were seven patients infected by genotype B strains with YMDD mutations and 13 by genotype C strains with YMDD mutations. Further research revealed that HCC occurred in 2 patients infected by genotype B strains with YMDD mutations and 11 infected by genotype C strains with YMDD mutations. The difference was statistically significant (P = 0.000). Unconditional logistic regression analysis revealed that patients infected by genotype C strains with spontaneous YMDD mutations had a 7.775-fold higher risk for the development of HBV-related HCC than patients infected by other type HBV strains (P = 0.013, 95%CI: 1.540-39.264).
CONCLUSION
Genotype C strains with spontaneous YMDD mutations are an independent risk factor for HCC in LC patients and are important for early warning of HCC.
目的
研究乙型肝炎病毒（HBV）基因型与自发 YMDD 突变和乙型肝炎病毒相关肝硬化肝癌（HCC）之间的关系。
方法
我们调查了 264 例未接受抗病毒药物治疗的肝硬化患者，其中 81 例患有 HCC。使用荧光杂交生物探针聚合酶链反应（PCR）和熔解曲线分析，使用 HBV YMDD 突变诊断试剂盒检测 YMDD 突变。使用实时 PCR 和基因型特异性 TaqMan 探针检测血清 HBV 基因型。根据数据类型使用 t 检验、χ(2)检验和非条件逻辑回归分析进行统计分析。
结果
在 HCC 组中，33 例（40.74%）、13 例（16.05%）和 11 例（13.58%）患者分别检测到基因型 C 株、自发 YMDD 突变和基因型 C 株伴 YMDD 突变。在肝硬化（LC）组中，33 例（18.03%）、7 例（3.83%）和 2 例（1.09%）患者分别检测到 HBV 基因型 C 株、自发 YMDD 突变和基因型 C 株伴 YMDD 突变。两组间基因型 C 株、自发 YMDD 突变和基因型 C 株伴 YMDD 突变差异有统计学意义（χ(2) = 15.441，P = 0.000；χ(2) = 11.983，P = 0.001；P = 0.000）。在 HCC 和 LC 组中，有 7 例患者感染 B 基因型伴 YMDD 突变，13 例感染 C 基因型伴 YMDD 突变。进一步研究发现，HBV 基因型 B 株伴 YMDD 突变感染患者中有 2 例发生 HCC，HBV 基因型 C 株伴 YMDD 突变感染患者中有 11 例发生 HCC。差异有统计学意义（P = 0.000）。非条件逻辑回归分析显示，感染 C 基因型伴自发 YMDD 突变的患者发生乙型肝炎病毒相关 HCC 的风险是感染其他 HBV 株的 7.775 倍（P = 0.013，95%CI：1.540-39.264）。
结论
基因型 C 株伴自发 YMDD 突变是 LC 患者 HCC 的独立危险因素，对 HCC 的早期预警具有重要意义。
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