HBV BCP区1762/1764位点变异对肝脏疾病进展及预后的影响

The effect of mutations in HBV basic core promoter A1762T/G1764A on the progression and prognosis of liver disease

目的:探讨乙型肝炎病毒BCP区A1762T/G1764A变异与肝脏疾病进展的关系。方法:收集78例慢性乙型肝炎患者(CHB)和125例慢性重型乙型肝炎患者(CSHB)的血清及临床资料,并对所有入组患者进行随访,采用聚合酶链反应扩增HBV BCP区基因片段,产物纯化后直接测序,检测BCP区T1762/A1764位点变异。结果:CSHB组患者A1762T、G1764A及A1762T+G1764A的变异频率分别为64.0%(80/125)、60.0%(75/125)、60.0%(75/125),CHB患者3种变异的变异频率分别为30.8%(24/78)、28.2%(22/78)、25.6%(20/78),CSHB组3种变异的变异频率均明显高于CHB组,差异有统计学意义(P<0.001)。125例CSHB患者随访48周,死亡组A1762T/G1764A位点变异频率明显高于存活组,差异有统计学意义(x^2=12.42,P<0.001);A1762T/G1764A位点变异组的患者累积存活率明显低于未变异组(x^2=9.742,P<0.01)。结论:HBV BCP区1762/1764位点变异可能会加重HBV感染后肝脏疾病病情,并且对慢性重型乙型肝炎的发病及预后可能起重要的作用。

Objective：To investigate the relationship between hepatitis B virus（HBV） basic core promoter（BCP） A1762T/G1764 A mutations and the progression of liver disease.Methods：Seventy- eight patients with chronic hepatitis B（CHB） and 125 patients with chronic severe hepatitis B（CSHB） were enrolled and venous blood samples were collected from all individuals.The genes covering HBV BCP were amplified by polymerase chain reaction（PCR）.The PCR products were subjected to direct sequencing and the mutations in 1762/1764 were determined by sequence analysis.Results：Single mutations（A1762T、G1764A）and combined mutations（A1762T/G1764A） were more frequently detected in CSHB patients than in CHB patients（P〈0.001）;The death group for 125 patients with CSHB had a higher mutation rate in A1762T/G1764 A than the survival group（x2 = 12.42,P〈0.001）.The 48-weeks cumulative survival rates of patients with mutation（A1762T/G1764A）were obviously lower than patients with no mutationx2 =9.742,P =0.002）. Conclusion：The double mutations in 1762/1764 might significantly affect the development of liver disease,also play a crucial role in predicting the prognosis of chronic severe hepatitis B.