肝癌根治术后拉米夫定抗病毒治疗对乙型肝炎相关性肝细胞癌患者无瘤生存时间的影响

Lamivudine antiviral treatment after radical surgery prolongs disease-free survival of patients with hepatitis B virus-related liver cancer

目的研究肝癌根治术后拉米夫定抗病毒治疗在延长乙型肝炎相关性肝细胞癌(HCC)患者无瘤生存时间中的应用。方法选取2014年3月-2016年3月于湖北医药学院附属东风医院行常规肝癌根治术的乙型肝炎相关性HCC患者120例,60例通过常规处理(A组)、60例通过拉米夫定抗病毒治疗(B组)。通过ELISA法检测所有患者的血清HBV DNA载量,计量资料组间比较采用t检验,计数资料组间比较采用χ~2检验,利用Kaplan-Meier法对比2组患者的无瘤生存率和复发率,Spearman相关分析探讨患者血清HBV DNA与生存期的关系。结果随访3年后发现所有患者中死亡71例(59.17%)(A组46例死于肿瘤,4例死于肝性脑病;B组20例死于肿瘤,1例死于肝性脑病)。B组复发率、3年内病死率均显著低于A组(48.33%vs 90.00%,35.00%vs83.33%,χ~2值分别为16.98、10.34,P值均<0.001)。B组平均无瘤生存期以及术后1、2、3年的无瘤生存率显著高于A组(t=9.82,χ~2值分别为7.87、11.43、7.98,P值均<0.001)。B组术后血清HBV DNA载量为(0.008 1±0.003 2)×105拷贝/ml,显著低于A组[(0.014 3±0.008 9)×105拷贝/ml](t=18.54,P<0.001)。A组术后1、2、3年的无瘤生存率对比中,HBV DNA载量≥1.0×105拷贝/ml的患者与HBV DNA载量<1.0×105拷贝/ml的患者存在明显差异(χ~2=8.57,P<0.05),进一步比较,1、2、3年无瘤生存率差异均有统计学意义(χ~2值分别为4.36、5.36、9.53,P值均<0.05);B组术后1、2、3年的无瘤生存率对比中,HBV DNA载量≥1.0×105拷贝/ml的患者与HBV DNA载量<1.0×105拷贝/ml的患者并无明显差异(P>0.05)。血清HBV DNA阳性表达与患者生存期呈正相关(r=0.67,P<0.001)。结论肝癌根治术后拉米夫定抗病毒治疗能够有效减轻患者血清HBV DNA水平,有助于延长乙型肝炎相关性HCC患者无瘤生存时间。

Objective To investigate whether lamivudine antiviral treatment after radical surgery can prolong disease-free survival of patients with hepatitis B virus-related liver cancer. Methods A total of 120 patients with hepatitis B virus-related liver cancer who underwent conventional radical surgery in Dongfeng Hospital Affiliated to Hubei Medical College from March 2014 to March 2016 were enrolled,and among these patients,60 were given conventional treatment（ group A） and 60 were given lamivudine antiviral treatment（ group B）.ELISA was used to measure serum HBV DNA level. The t-test was used for comparison of continuous data between groups,the chi-square test was used for comparison of categorical data between groups,the Kaplan-Meier method was used to compare disease-free survival rate and recurrence rate between groups,and the Spearman method was used to investigate the correlation between serum HBV DNA level and survival time. Results According to the results of the 3-year follow-up,71 patients（ 59. 17%） died（ group A： 46 patients died of tumor and 4 died of hepatic encephalopathy; group B： 20 died of tumor and 1 died of hepatic encephalopathy）. Compared with group A,group B had significantly lower recurrence rate（ 48. 33% vs 90. 00%,χ~2= 16. 98,P 0. 001） and mortality rate within 3 years（ 35. 00%vs 83. 33%,χ~2= 10. 34,P 0. 001）. Group B had significantly higher mean disease-free survival time and 1-,2-,and 3-year disease-free survival rates than group A（ t = 9. 82,χ~2= 7. 87,11. 43,and 7. 98,all P 0. 001）. After surgery,group B had a significantly lower serum HBV DNA load than group A [（ 0. 008 1 ± 0. 003 2） × 105copies/ml vs（ 0. 014 3 ± 0. 008 9） × 105copies/ml,t = 18. 54,P 0. 001]. In group A,there were significant differences in 1-,2-,and 3-year disease-free survival rates between patients with serum HBV DNA load ≥1. 0 × 105copies/ml and those with serum HBV DNA load 1. 0 × 105copies/ml（ χ~2= 8. 57,P 0. 05）,and further analysis showed that there were significant differences in 1-,2-,and 3-year disease-free survival rates（ χ~2= 4. 36,5. 36,and 9. 53,P 0. 05）; in group B,there were no significant differences in 1-,2-,and 3-year disease-free survival rates between these two groups of patients（ P 0. 05）. Serum HBV DNA expression was positively correlated with patients＇ survival time（ r = 0. 67,P 0. 001）. Conclusion Lamivudine antiviral therapy after radical surgery can effectively reduce serum HBV DNA level,and helps to prolong the disease-free survival time of patients with hepatitis B virus-related liver cancer.