长期核苷(酸)类抗病毒治疗的乙型肝炎肝硬化患者肝癌发生相关因素研究

Risk factors of liver cancer occurrence in patients with hepatitis B liver cirrhosis receiving long-term nucleot(s)ide antiviral therapy

目的探讨长期接受核苷酸抗病毒治疗的乙型肝炎肝硬化患者肝癌发生的相关危险因素。方法2002年5月~2015年5月接受核苷(酸)类抗病毒治疗的乙型肝炎肝硬化患者417例,平均抗病毒治疗时间为(9.11±2.09)年。记录观察期内原发性肝癌发生情况。采用多元Logistics回归分析导致肝癌发生的危险因素。结果在观察期内,本组417例乙型肝炎肝硬化患者发生原发性肝癌57例(13.7)%;肝癌组在有肝癌家族史、长期饮酒、Child-Pugh C级、未应用一线抗病毒药物、抗病毒治疗后血清HBV DNA水平仍大于20 IU/ml的比率显著高于未发生肝癌组(P<0.05);多因素Logistic分析显示存在肝癌家族史(OR=1.568,95%CI为1.074~2.289,P=0.020)、长期饮酒史(OR=1.791,95%CI为1.227~2.615,P=0.003)、Child-Pugh C级(OR=1.598,95%CI为1.095~2.333,P=0.016)、未应用一线抗病毒药物(OR=1.476,95%CI为0.997~2.168,P=0.047)和抗病毒治疗后血清HBV DNA水平仍未转阴(OR=1.480,95%CI为1.014~2.160,P=0.043)为肝癌发生的独立危险因素。结论本研究经过长期随访观察,发现有肝癌家族史、长期饮酒、Child-Pugh分级C级、未应用一线抗病毒药物治疗和抗病毒治疗后血清HBV DNA仍大于20 IU/ml是导致乙型肝炎肝硬化患者发生肝癌的危险因素,选择一线抗病毒药物治疗、戒酒、改善肝功能状态可能减少肝癌的发生,值得认真对待。

Objective The aim of this study was to explore the risk factors of liver cancer occurrence in patients with hepatitis B liver cirrhosis receiving long-term nucleot(s)ide antiviral therapy.Methods A total of 417 patients with hepatitis B-induced liver cirrhosis receiving nucleos(t)ide antiviral therapy were followed-up from May 20012 to May 2015,and they underwent imaging check-up regularly for the findings of primary liver cancer(PLC).Multivariate Logistic analysis was applied to find the risk factors of PLC occurrence.Results During the followed-up period,the PLC was found in 57 patients with liver cirrhosis(13.7)%;the univariate Logistic analysis showed that the percentages of family history of liver cancer,long-term alcohol consumption,Child-Pugh class C,non-first line medicine for antiviral therapy and serum HBV DNA greater than 20 IU/ml in patients with PLC were significantly higher than that in cirrhotic patients(P<0.05);the multivariate Logistic analysis demonstrated that family history of liver cancer(OR=1.568,95%CI:1.074-2.289,P=0.020),long-term alcohol consumption(OR=1.791,95%CI:1.227-2.615,P=0.003),Child-Pugh class C(OR=1.598,95%CI:1.095-2.333,P=0.016),non-first line antiviral medicine therapy(OR=1.476,95%CI:0.997-2.168,P=0.047)and still positive serum HBV DNA loads after antiviral therapy(OR=1.480,95%CI:1.014-2.160,P=0.043)were the independent risk factors for liver cancer occurrence.Conclusion We conclude this study with findings of liver cancer family history,long-term drinking,Child-Pugh class C liver functions,not taking first-line antiviral medicines and serum HBV DNA level greater than 20 IU/ml after antiviral therapy being the risk factors of PLC happening,which hints administration of first-line antiviral therapy to obtain sustained virologic response,abstaining drinking and improvement of liver functions appropriately might decrease the liver cancer happening in patients with hepatitis B-induced liver cirrhosis.