Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Department of Health Care Management, College of Management; and Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan.
Aliment Pharmacol Ther. 2020 Dec;52(11-12):1695-1706. doi: 10.1111/apt.16116. Epub 2020 Oct 27.
Comparative long-term efficacy of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) for prevention of disease progression to hepatocellular carcinoma (HCC) among high-risk patients with chronic hepatitis B (CHB)-related compensated cirrhosis is controversial.
To compare the long-term efficacy of ETV and TDF in HCC prevention in patients with CHB-related cirrhosis, and to evaluate predictive risk factors for HCC development.
From January 2008 to March 2018, 894 treatment-naïve patients with CHB-related compensated cirrhosis on ETV or TDF were enrolled based on the longitudinal cohort study. Data were originally collected for 7.3 years of follow-up or after the launch of TDF in 2011. Only the 5-year cumulative incidence and risk factors of HCC were assessed.
Total 678 and 216 patients received ETV and TDF, respectively. The cumulative risk of HCC at 1, 3 and 5 years of follow-up was 1.6%, 11.3% and 18.7%, respectively, in the ETV group; and 0.9%, 6.7% and 10.7%, respectively, in the TDF group (P = 0.0305). Univariate and adjusted-multivariable models revealed that platelet count, alpha-fetoprotein (AFP) levels and upper gastrointestinal (UGI) varices were independent risk factors for HCC development. TDF resulted in risk of HCC development compared to ETV with adjusted hazard ratios (aHRs) of 0.66 (95% confidence interval [CI]:0.40, 1.08; P = 0.0971), 0.69 (95% CI: 0.42, 1.14; P = 0.1488) and 0.66 (95% CI: 0.38, 1.14; P = 0.1407) under stepwise selection, propensity score adjustment, and propensity score matching multivariable models, respectively.
For treatment-naïve patients with CHB-related compensated cirrhosis with 5-year follow-up, after variable adjustments, propensity score approaches and subgroup analyses, TDF showed a lower rate of HCC development that did not reach statistical significance, compared to the ETV.
对于慢性乙型肝炎（CHB）相关代偿性肝硬化的高危患者，恩替卡韦（ETV）和替诺福韦酯富马酸（TDF）预防疾病进展为肝细胞癌（HCC）的长期疗效存在争议。
比较 ETV 和 TDF 在预防 CHB 相关肝硬化患者 HCC 中的长期疗效，并评估 HCC 发展的预测风险因素。
本研究基于纵向队列研究，于 2008 年 1 月至 2018 年 3 月期间纳入了 894 例接受 ETV 或 TDF 治疗的初治 CHB 相关代偿性肝硬化患者。数据最初采集了 7.3 年的随访，或在 2011 年 TDF 上市后采集。仅评估了 HCC 5 年累积发生率和风险因素。
ETV 组和 TDF 组分别有 678 例和 216 例患者接受了治疗。ETV 组的 1、3 和 5 年 HCC 累积风险分别为 1.6%、11.3%和 18.7%；TDF 组分别为 0.9%、6.7%和 10.7%（P=0.0305）。单因素和多因素调整模型显示，血小板计数、甲胎蛋白（AFP）水平和上消化道（UGI）静脉曲张是 HCC 发展的独立危险因素。与 ETV 相比，TDF 导致 HCC 发展的风险增加，调整后的风险比（aHR）分别为 0.66（95%置信区间 [CI]：0.40，1.08；P=0.0971）、0.69（95% CI：0.42，1.14；P=0.1488）和 0.66（95% CI：0.38，1.14；P=0.1407），在逐步选择、倾向评分调整和倾向评分匹配多因素模型中。
对于接受初治 CHB 相关代偿性肝硬化治疗且随访时间达到 5 年的患者，在进行了各种变量调整、倾向评分方法和亚组分析后，与 ETV 相比，TDF 显示 HCC 发生率较低，但差异无统计学意义。
