Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea.
Clin Mol Hepatol. 2024 Jul;30(3):500-514. doi: 10.3350/cmh.2024.0055. Epub 2024 May 10.
BACKGROUND/AIMS: Chronic hepatitis B (CHB) is related to an increased risk of extrahepatic malignancy (EHM), and antiviral treatment is associated with an incidence of EHM comparable to controls. We compared the risks of EHM and intrahepatic malignancy (IHM) between entecavir (ETV) and tenofovir disoproxil fumarate (TDF) treatment.
Using data from the National Health Insurance Service of Korea, this nationwide cohort study included treatment-naïve CHB patients who initiated ETV (n=24,287) or TDF (n=29,199) therapy between 2012 and 2014. The primary outcome was the development of any primary EHM. Secondary outcomes included overall IHM development. E-value was calculated to assess the robustness of results to unmeasured confounders.
The median follow-up duration was 5.9 years, and all baseline characteristics were well balanced after propensity score matching. EHM incidence rate differed significantly between within versus beyond 3 years in both groups (P<0.01, Davies test). During the first 3 years, EHM risk was comparable in the propensity score-matched cohort (5.88 versus 5.84/1,000 person-years; subdistribution hazard ratio [SHR]=1.01, 95% confidence interval [CI]=0.88-1.17, P=0.84). After year 3, however, TDF was associated with a significantly lower EHM incidence compared to ETV (4.92 versus 6.91/1,000 person-years; SHR=0.70, 95% CI=0.60-0.81, P<0.01; E-value for SHR=2.21). Regarding IHM, the superiority of TDF over ETV was maintained both within (17.58 versus 20.19/1,000 person-years; SHR=0.88, 95% CI=0.81-0.95, P<0.01) and after year 3 (11.45 versus 16.20/1,000 person-years; SHR=0.68, 95% CI=0.62-0.75, P<0.01; E-value for SHR=2.30).
TDF was associated with approximately 30% lower risks of both EHM and IHM than ETV in CHB patients after 3 years of antiviral therapy.
背景/目的：慢性乙型肝炎（CHB）与肝外恶性肿瘤（EHM）的风险增加有关，抗病毒治疗与对照相比，EHM 的发病率相当。我们比较了恩替卡韦（ETV）和替诺福韦酯二吡呋酯（TDF）治疗之间 EHM 和肝内恶性肿瘤（IHM）的风险。
使用来自韩国国家健康保险服务的数据，这项全国性队列研究包括 2012 年至 2014 年间接受 ETV（n=24287）或 TDF（n=29199）治疗的初治 CHB 患者。主要结局是任何原发性 EHM 的发展。次要结局包括总体 IHM 发展。计算 E 值以评估结果对未测量混杂因素的稳健性。
中位随访时间为 5.9 年，经过倾向评分匹配后，所有基线特征均得到很好的平衡。两组中，在 3 年以内与 3 年以后相比，EHMs 的发生率差异均有统计学意义（P<0.01，Davies 检验）。在最初的 3 年内，匹配后的队列中 EHM 的风险相当（5.88 与 5.84/1000 人年；亚分布风险比[SHR]=1.01，95%置信区间[CI]=0.88-1.17，P=0.84）。然而，3 年后，TDF 与 ETV 相比，EHMs 的发生率显著降低（4.92 与 6.91/1000 人年；SHR=0.70，95%CI=0.60-0.81，P<0.01；SHR 的 E 值=2.21）。关于 IHM，TDF 优于 ETV 的优势在 3 年内（17.58 与 20.19/1000 人年；SHR=0.88，95%CI=0.81-0.95，P<0.01）和 3 年后（11.45 与 16.20/1000 人年；SHR=0.68，95%CI=0.62-0.75，P<0.01；SHR 的 E 值=2.30）均得到维持。
抗病毒治疗 3 年后，与 ETV 相比，TDF 与 CHB 患者 EHM 和 IHM 的风险降低约 30%相关。
