Long-Term Entecavir Treatment Reduces Hepatocellular Carcinoma Incidence in Patients With Hepatitis B Virus Infection
Long-Term Entecavir Treatment Reduces Hepatocellular Carcinoma Incidence in Patients With Hepatitis B Virus Infection
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DOI：
10.1002/hep.26180
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发表时间：
2013-07-01
期刊：
影响因子：
13.5
通讯作者：
Kumada, Hiromitsu
中科院分区：
文献类型：
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作者：
Hosaka, Tetsuya;Suzuki, Fumitaka;Kumada, Hiromitsu
慢性乙型肝炎病毒（HBV）感染可导致肝硬化和肝细胞癌（HCC）。抗病毒药物被认为可以减少HCC的发展，但拉米夫定（LAM）等药物具有很高的耐药性。我们比较了472例恩替卡韦（ETV）治疗患者和1143例未治疗的HBV患者（对照组）的HCC发生率。倾向评分匹配消除了基线差异，导致每个队列的样本量为316例患者。ETV组药物突变耐药率为0.8%（4/472）。ETV组和对照组5年HCC累计发病率分别为3.7%和13.7% （P < 0.001）。Cox比例风险回归分析，调整了一些已知的HCC危险因素，显示ETV组患者发生HCC的可能性低于对照组（风险比：0.37；95%可信区间：0.15-0.91;P = 0.030）。两个队列应用于三个先前报道的风险量表，并根据年龄、性别、肝硬化状态、丙氨酸转氨酶水平、乙型肝炎e抗原、基线HBV DNA、白蛋白和胆红素生成风险评分。最大的HCC风险降低发生在相应风险量表得分较高的高危患者中。在亚组分析中，我们比较了核苷(t)类似物的治疗效果，其中包括匹配的未经抢救治疗的lam治疗患者（n = 182）。我们发现，与对照组相比，etv治疗的肝硬化患者的HCC抑制效果（P < 0.001）大于未抢救的lam治疗（P = 0.019）。结论：长期ETV治疗可降低hbv感染患者HCC的发生率。在HCC风险较高的患者中，治疗效果更好。
Chronic hepatitis B virus (HBV) infection leads to cirrhosis and hepatocellular carcinoma (HCC). Antiviral agents are thought to reduce HCC development, but agents such as lamivudine (LAM) have a high rate of drug resistance. We compared the incidence of HCC in 472 entecavir (ETV)-treated patients and 1,143 nontreated HBV patients (control group). Propensity score matching eliminated the baseline differences, resulting in a sample size of 316 patients per cohort. The drug mutation resistance was 0.8% (4/472) in the ETV group. The cumulative HCC incidence rates at 5 years were 3.7% and 13.7% for the ETV and control groups, respectively (P < 0.001). Cox proportional hazard regression analysis, adjusted for a number of known HCC risk factors, showed that patients in the ETV group were less likely to develop HCC than those in the control group (hazard ratio: 0.37; 95% confidence interval: 0.15-0.91; P = 0.030). Both cohorts were applied in three previously reported risk scales and risk scores were generated based on age, gender, cirrhosis status, levels of alanine aminotransferase, hepatitis B e antigen, baseline HBV DNA, albumin, and bilirubin. The greatest HCC risk reduction occurred in high-risk patients who scored higher on respective risk scales. In sub analyses, we compared treatment effect between nucleos(t)ide analogs, which included matched LAM-treated patients without rescue therapy (n = 182). We found HCC suppression effect greater in ETV-treated (P < 0.001) than nonrescued LAM-treated (P = 0.019) cirrhosis patients when they were compared with the control group. Conclusion: Long-term ETV treatment may reduce the incidence of HCC in HBV-infected patients. The treatment effect was greater in patients at higher risk of HCC.