CALM研究表明，拉米夫定治疗3年略能降低晚期肝纤维化或肝硬化患者的肝细胞癌（HCC）风险。因此，我们的目的是探讨乙型肝炎相关性肝硬化患者应用恩替卡韦长期治疗减少肝细胞癌发生的疗效，之前中期报告显示，与历史对照患者相比，治疗组患者HCC发生率呈现临界性显著性降低（P =0.053），大概由于样本量相对小，随访持续时间较短。

材料和方法 

在这份C-TEAM（肝硬化台湾恩替卡韦多中心）研究的随访报告中，我们纳入了1983年至2008年间未进行抗病毒治疗的HBV相关性肝硬化患者（历史对照组）和自2008年以来接受长期恩替卡韦单药治疗的患者（恩替卡韦组）。所有患者的基线血清HBV-DNA水平>2000 IU/ mL，纵向随访临床结果，包括进展为肝细胞癌和肝硬化并发症。 

研究结果 

截至2014年3月31日，我们在24个学术中心招募了对照组503例患者，恩替卡韦组1123例患者。两组间性别、基线HBeAg状态、α-甲胎蛋白和HBV-DNA水平是相当的。相较于历史对照，治疗组患者年龄显著更大，肝脏疾病更晚期。对照组和恩替卡韦组随访平均时间分别为6.8年和3.6年。校正年龄后，应用Cox比例回归模型进行多变量分析显示，男性、未治疗、白蛋白水平较低和血小板计数较低是预测HCC进展的独立终生风险。恩替卡韦治疗可降低肝硬化患者60％的HCC风险（校正风险比：0.40，95％CI：0.27-0.60）。进一步分析表明，与未治疗对照相比，恩替卡韦治疗显著降低自发性细菌性腹膜炎的新发展。 

结论 

在这项大规模的队列研究中，长期恩替卡韦治疗显著降低HBV相关性肝硬化患者HCC和自发性细菌性腹膜炎的发展。

英文原文

Reduction of hepatocellular carcinoma in hepatitis B-related cirrhosis patients with long-term entecavir therapy - A follow-up report of C-TEAM study （摘要号：LB-30）

Background and Aims：The CALM study showed that lamivudine marginally reduces hepatocellular carcinoma (HCC) risk in patients with advanced fibrosis or cirrhosis at 3 years of therapy. We thus aimed to investigate the reduction of HCC in hepatitis B-related cirrhosis patients with long-term entecavir therapy, and the previous interim report showed a borderline significant reduction of HCC incidence (P= 0.053) in treated patients compared to historical controls, probably due to the relatively small sample size and shorter follow-up duration. 

Materials and Methods：In this follow-up report of C-TEAM (Cirrhosis Taiwanese Entecavir Multicenter) study, we enrolled HBV-related cirrhosis patients without antiviral treatment during 1983-2008 (historical control group) and those who received long-term entecavir monotherapy since 2008 (entecavir group). All patients had baseline serum HBV-DNA level > 2,000 IU/mL and were followed longitudinally for clinical outcomes including HCC development and cirrhotic complications.

Results：As of March 31st, 2014, we enrolled 503 patients in the control group and 1123 in the entecavir group from 24 academic centers. The gender and baseline HBeAg status, alfa-fetoprotein and HBV-DNA levels were comparable between these two groups. Compared to historical controls, treated patients were significantly older and had more advanced liver diseases. The mean duration of follow-up was 6.8 and 3.6 years in the control and entecavir groups, respectively. After adjusting for age, the multivariate analysis by Cox proportional regression model showed that male gender, no treatment, lower albumin level and lower platelet count were independent lifetime risks predictive of HCC development. Entecavir treatment was associated with 60% reduction of HCC risk (adjusted hazard ratio: 0.40, 95% CI: 0.27-0.60) in cirrhosis patients. Further analysis indicated that entecavir treatment significantly reduce new development of spontaneous bacterial peritonitis compared with untreated controls.

Conclusion：In this large cohort study, long-term entecavir therapy significantly reduced the development of HCC and spontaneous bacterial peritonitis in hepatitis B-related cirrhosis patients.

查看会议专题》》》第65届美国肝病学会年会（AASLD2014）

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