CAJ | 학술논문

目的分析核苷(酸)类似物有效抗病毒治疗过程中乙型肝炎肝硬化患者发生肝细胞癌(HCC)的高风险因素.方法所有患者均来自一项前瞻性多中心对照随机开放试验.2007年6月至2009年2月,8家医院的乙型肝炎代偿性肝硬化患者接受初始拉米夫定(LAM)或阿德福韦酯(ADV)单药治疗,并根据治疗过程中的应答状况最终转为两药联合治疗的抗病毒方案,随访至192周.观察患者的基线状态、病毒学应答、病毒耐药变异,探讨HCC发生的相关危险因素.采用秩和检验、Fisher确切概率法、Log-rank检验和Cox回归.结果 207例患者在192周随访中,14例(6.76％)发生HCC的患者为HCC组,未发生HCC者中有123例留存有完整血清可进行耐药位点检测,为非HCC组.患者性别、基线生物化学指标、病毒学特征,以及治疗中的HBsAg定量水平和病毒学应答均与HCC的发生无显著相关.HCC患者较非HCC患者发生更多rtM204V/I变异(64.29％比29.27％,P=0.014).Cox回归分析发现,起始治疗时年龄≥50岁和发生rtM204V/I变异是发生HCC的风险因子(年龄:HR=1.093,95％CI:1.024～1.166;发生rtM204V/I变异:HR=4.28,95％CI:1.394～13.133).结论年龄≥50岁和存在rtM204V/I变异是核苷(酸)类似物有效抗病毒治疗过程中乙型肝炎肝硬化患者发生HCC的危险因素.
목적 분석핵감(산)유사물유효항병독치료과정중을형간염간경화환자발생간세포암(HCC)적고풍험인소.방법 소유환자균래자일항전첨성다중심대조수궤개방시험.2007년6월지2009년2월,8가의원적을형간염대상성간경화환자접수초시랍미부정(LAM)혹아덕복위지(ADV)단약치료,병근거치료과정중적응답상황최종전위량약연합치료적항병독방안,수방지192주.관찰환자적기선상태、병독학응답、병독내약변이,탐토HCC발생적상관위험인소.채용질화검험、Fisher학절개솔법、Log-rank검험화Cox회귀.결과 207례환자재192주수방중,14례(6.76％)발생HCC적환자위HCC조,미발생HCC자중유123례류존유완정혈청가진행내약위점검측,위비HCC조.환자성별、기선생물화학지표、병독학특정,이급치료중적HBsAg정량수평화병독학응답균여HCC적발생무현저상관.HCC환자교비HCC환자발생경다rtM204V/I변이(64.29％비29.27％,P=0.014).Cox회귀분석발현,기시치료시년령≥50세화발생rtM204V/I변이시발생HCC적풍험인자(년령:HR=1.093,95％CI:1.024～1.166;발생rtM204V/I변이:HR=4.28,95％CI:1.394～13.133).결론 년령≥50세화존재rtM204V/I변이시핵감(산)유사물유효항병독치료과정중을형간염간경화환자발생HCC적위험인소.
Objective To analyze the risk factors for the development of hepatocellular carcinoma (HCC) in patients with hepatitis B cirrhosis under effective nucleos(t)ide analog therapy.Methods All cases were from a prospective,multicentre,randomized controlled,open-label trial.From June 2007 to February 2009,eligible hepatitis B cirrhosis patients from eight medical institutions were started with either lamivudine (LAM) or adefovir dipivoxil (ADV) monotherapy.All patients switched to LAM plus ADV combination therapy later according to the on-treatment virological responses and were followed up until week 192.Baseline characteristics of patients,on-treatment virological responses and drug resistance mutations were observed and risk factors associated with HCC development were analyzed.Statistical analyses included Wilcoxon-Mann-Whitney test,Fisher exact test,Log-rank test and Cox proportional hazards regression.Results During 192 weeks of follow-up,14 of the 207 patients developed HCC,and were classified into HCC group.A total of 123 cases who saved serums for detecting drug resistance mutation did not developed HCC and were classified into non-HCC group.Gender,biochemical indexes and virological characteristics at baseline,as well as the on-treatment hepatitis B surface antigen (HBsAg) levels and virological responses were found of no significant association with the development of HCC.The rtM204V/I mutation rate in patients who developed HCC was higher than those who did not (64.29％ vs 29.27％,P=0.014).Cox proportional hazards regression showed that age ≥50 years at the initiation of anti-viral therapy and rtM204V/I mutation were two independent risk factors associated with HCC(age:HR=1.093,95％CI:1.024-1.166; rtM204V/I mutation:HR=4.28,95％CI:1.394-13.133).Conclusion Age ≥50 years and rtM204V/I mutation are risk factors associated with HCC development in patients with hepatits B cirrhosis under effective antiviral therapy with nucleos(t)ide analog.