摘要
目的回顾性分析长期经核苷(酸)类似物(NAs)治疗并全程管理的乙型肝炎肝硬化(LC)患者发生肝癌的危险因素。方法研究对象来源于2004年2月至2019年9月广西医科大学第一附属医院感染性疾病科慢性乙型肝炎、肝硬化抗病毒治疗随访队列,选择符合入选条件的LC患者入组。采用寿命表法计算肝癌发生率情况;多因素Cox模型分析可能影响LC患者发生肝癌的危险因素;LC发生肝癌患者进行亚组分析,评估依从性对抗病毒治疗效果的影响。对率的比较采用χ2检验。结果198例NAs治疗的LC患者中位随访时间6.0年(1.0~15.3年)。至末次访视:(1)LC患者有16.2%(32/198)进展为肝癌,其1、3、5、7、9年肝癌累积发生率分别0、8.9%、14.3%、18.6%、23.4%,年均发生率为3.1%;32例肝癌患者中68.7%为小肝癌(22/32)。(2)单因素Cox模型分析显示LC有无结节、基线是否一线用药、肝癌家族史、患者依从性四个因素与肝癌发生相关;多因素Cox模型分析结果显示患者依从性差和基线非一线用药是肝癌发生的危险因素。(3)Log-Rank检验亚组结果分析表明有硬化结节患者5年肝癌累积发生率显著高于没有硬化结节患者(21.7%与11.5%,P=0.029);非一线用药患者5年肝癌累积发生率显著高于一线用药患者(22.0%与8.2%,P=0.003);依从性差的患者5年肝癌累积发生率显著高于依从性好的患者(21.3%与12.7%,P=0.014);有肝癌家族史的患者5年肝癌累积发生率显著高于无肝癌家族史的患者(22.3%与8.1%,P=0.006)。(4)依从性好的患者与依从性差的患者比较,末次HBV DNA阴转率高(98.7%与87.8%,P=0.005),病毒学突破率低(12.1%与29.3%,P=0.007)。结论长期NAs抗病毒治疗可以降低肝癌发生风险,但不能完全阻止肝癌发生,特别是有肝癌家族史、基线有硬化结节的患者发生肝癌的风险更高,而全程管理可以提高患者依从性,确保抗病毒治疗疗效,而降低肝癌的发生风险,实现早期发现�
Objective To retrospectively analyze the risk factors for the development of liver cancer in patients with hepatitis B-related liver cirrhosis(LC)treated and fully managed with long-term nucleos(t)ide analogues(NAs).Methods The study subjects were derived from the follow-up cohort of chronic hepatitis B and liver cirrhosis who received antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Guangxi Medical University from February 2004 to September 2019.LC patients who met the inclusion criteria were enrolled.The life-table method was used to calculate the incidence of liver cancer.Multivariable Cox regression model was used to analyze the risk factors that may affect the development of liver cancer in patients with LC.A subgroup analysis was conducted in liver cirrhotic patients who developed liver cancer to evaluate the effectiveness of antiviral treatment compliance.The 2 test was used for rate comparison.Results The median follow-up time of 198 LC cases treated with NAs was 6.0 years(1.0-15.3 years).By the end of the visit:(1)16.2%(32/198)of LC patients had developed liver cancer,and the cumulative incidence of liver cancer in 1,3,5,7,and 9 years were 0,8.9%,14.3%,18.6%,and 23.4%,respectively,with an average annual incidence of 3.1%.Among the 32 cases with liver cancer,68.7%had developed small liver cancer(22/32).(2)Univariate Cox model analysis showed that the development of liver cancer was related to four factors,i.e.,the presence or absence of LC nodules,whether the baseline was first-line medication,the family history of liver cancer,and patient compliance.The results of multivariate Cox model analysis showed that poor patient compliance and baseline non-first-line medication were risk factors for liver cancer.(3)The results of log-rank test subgroup analysis showed that the 5-year cumulative incidence of liver cancer in patients with hardened nodules was significantly higher than that of patients without hardened nodules(21.7%vs.11.5%,P=0.029).The 5-year cumulative
作者
臧伟伟
苏明华
零小樟
王荣明
曹汴川
吴育龙
邓德丽
韦慧兰
梁先帅
江建宁
Zang Weiwei;Su Minghua;Ling Xiaozhang;Wang Rongming;Cao Bianchuan;Wu Yulong;Deng Deli;Wei Huilan;Liang Xianshuai;Jiang Jianning(Department of Infectious Diseases,the First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China)
出处
《中华肝脏病杂志》
CAS
CSCD
北大核心
2020年第8期679-685,共7页
Chinese Journal of Hepatology
基金
国家自然科学基金项目(81960115)
"十三五"艾滋病和病毒性肝炎等重大传染病防治科技重大专项(2017ZX10202201)
广西病毒性肝炎防治研究重点实验室开放课题基金项目(GXCDCKL201802)
区域性高发肿瘤早期防治研究教育部重点实验室自主课题(GKE2018-05、GKE2019-04)。
关键词
肝炎
乙型
慢性
肝硬化
肝细胞癌
核苷(酸)类似物
Hepatitis B,chronic
Liver cirrhosis
Hepatocellular carcinoma
Nucleoside(acid)analogues
