【摘要】 [目的]研究乙型肝炎病毒(HBV)基因型对应的BCP区变异与肝细胞癌(HCC)发生之间的关系。[方法]采用队列研究设计,对慢性HBV感染者进行随访观察,采用多重PCR法和巢式多重PCR法进行HBV基因型分型。变异检测采用PCR扩增后测序。[结果]HBV基因型B感染者平均随访8.52(IQR:6.67~10.75)年,HCC发生率为6.55/1 000人年,HBV基因型C感染者平均随访8.87(IQR:6.85~11.33)年,HCC发生率为11.63/1 000人年,两组之间差异有统计学意义(P=0.006)。HBV基因型B感染者中,年龄(≥60岁)、肝硬化能够增加HCC发生的危险性;HBV基因型C感染者中,男性、年龄(≥40岁)、肝硬化、C1653T、T1753V、A1762T/G1764A突变能够增加HCC发生的危险性,干扰素治疗能够降低HCC发生的危险性。在HBV基因型C感染者中,对于发生A1762T/G1764A突变(HR=0.21,P=0.008)和未发生C1653T(HR=0.17,P=0.013)、T1753V(HR=0.08,P=0.012)突变者使用干扰素治疗能够显著降低HCC发生的危险性。[结论]HBV基因型及变异与HCC发生密切相关。HBV基因型C感染者中,发生A1762T/G1764A突变者应优先接受抗病毒治疗;而发生C1653T和T1753V突变者应该密切进行监测以早期发现HCC,尽早手术切除。更多还原

【Abstract】 [Objective] To investigate the relationship between hepatitis B virus( HBV) genotype and their mutations on the development of hepatocellular carcinoma( HCC). [Methods] A cohort study on patients with chronic HBV infection was followed up. HBV genotypes were identified by nested multiplex PCR and multiplex PCR. And HBV mutations in the basic core promoter region were sequencing by PCR amplification. [Results] The patients infected with genotype B were followed up for an average of 8. 52 years( IQR: 6. 67- 10. 75),of whom the incidence of HCC was 6. 55 /1 000 person- years. After follow up with an average of 8. 87 years( IQR: 6. 85- 11. 33),the incidence of HCC was 11. 63 /1 000person- years for the patients infected with genotype C,which were significantly higher than those infected with genotype B( P = 0. 006). In genotype B HBV infected patients,age( ≥60 years),cirrhosis can increase the risk of HCC,and in genotype C patients,male,age( ≥ 40 years),cirrhosis,C1653 T,T1753V,A1762 T / G1764 A mutation as well. Interferon therapy can reduce the risk of HCC. In genotype C group,interferon treatment reduced HCC risk in patients carrying A1762 T / G1764 A mutation( HR = 0. 21,P = 0. 008) and in those without T1753V( HR = 0. 08,P = 0. 012) and C1653 T mutation( HR = 0. 17,P = 0. 013). [Conclusion] HBV genotypes and mutation are closely associated with HCC. Patients infected with genotype C,carrying 1762 T / G1764 A mutation should be given priority of receiving antiviral treatments in order to prevent HCC; those carrying C1653 T or T1753 V mutation should be monitored closely to detect early HCC and receive timely surgical resection.更多还原