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[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。
[Objective] To study the relationship between the BCP mutation corresponding to hepatitis B virus (HBV) genotype and the occurrence of hepatocellular carcinoma (HCC). [Methods] A cohort study was designed to observe the patients with chronic HBV infection. The genotypes of HBV were detected by multiplex PCR and nested multiplex PCR. Mutation detection using PCR amplification sequencing. [Results] The average incidence of HCC was 6.55 / 1000 person-years in patients with HBV genotype B infection after an average follow-up of 8.52 (IQR: 6.67-10.75) years. HBV genotype C infection was followed up for a mean of 8.87 years (IQR: 6.85 to 11.33) The incidence of HCC was 11.63 per 1,000 person-years, with a significant difference between the two groups (P = 0.006). HBV genotype B infection, age (≥ 60 years), cirrhosis can increase the risk of HCC; HBV genotype C infection in men, age (≥ 40 years), cirrhosis, C1653T, T1753V, A1762T / G1764A mutation can increase the risk of HCC, interferon therapy can reduce the risk of HCC. Among patients with HBV genotype C infection, those with mutations of A1762T / G1764A (HR = 0.21, P = 0.008) and those without C1653T (HR = 0.17, P = 0.013) and T1753V (HR = 0.08, P = 0.012) Treatment with interferon can significantly reduce the risk of developing HCC. [Conclusion] The genotype and mutation of HBV are closely related to the occurrence of HCC. HBV genotype C infection, the occurrence of A1762T / G1764A mutation should give priority to receiving antiviral therapy; and C1653T and T1753V mutation should be closely monitored to early detection of HCC, as soon as possible surgical resection.