Stanford University School of Medicine, Stanford, CA, USA.
Gilead Sciences Inc., Foster City, CA, USA.
Aliment Pharmacol Ther. 2022 Apr;55(7):828-835. doi: 10.1111/apt.16786. Epub 2022 Feb 8.
Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are the first-line treatment agents for chronic hepatitis B virus (HBV). Recently, whether the degree to which the risk of hepatocellular carcinoma (HCC) may be reduced by ETV vs TDF has been debated. We compared the incidence of HCC among treatment-naïve patients receiving TDF vs ETV in the United States.
From a large administrative medical claims database of commercially insured patients, we identified 166,933 adults with a diagnosis of chronic hepatitis B and a minimum of 12 months of prior enrolment, of whom 3934 and 6127 initiated ETV and TDF respectively. Fine-Gray hazard regression models incorporating treatment propensity scores (PS) were used to estimate the risk of HCC incidence associated with TDF vs ETV; variables considered for adjustment included demographic characteristics, concomitant medication use and baseline comorbidities, as well as competing events including liver transplantation and medication changes.
After PS weighting, the TDF and ETV groups were well-matched. During the follow-up, 90 patients developed HCC, including 50 receiving ETV and 40 receiving TDF, giving rise to crude incidence rates of 0.62 per 100 person-years (PY) and 0.30 per 100 PY respectively. In PS-weighted, multivariable analysis, TDF was associated with a subdistribution hazard ratio for HCC of 0.58 (95% confidence interval [CI]: 0.38-0.89) compared to ETV. Results were similar when patients ≥40 years and men and women were analysed separately.
Among commercially insured, treatment-naïve patients with chronic hepatitis B in the United States, treatment with TDF was associated with significantly lower risk of HCC than ETV.
恩替卡韦（ETV）和富马酸替诺福韦二吡呋酯（TDF）是慢性乙型肝炎病毒（HBV）的一线治疗药物。最近，关于 ETV 降低肝细胞癌（HCC）风险的程度是否优于 TDF 存在争议。我们比较了美国初治患者接受 TDF 与 ETV 治疗时 HCC 的发病率。
我们从一个大型商业保险患者的行政医疗索赔数据库中，确定了 166933 名患有慢性乙型肝炎且至少有 12 个月既往入组记录的成年人，其中 3934 名和 6127 名分别开始使用 ETV 和 TDF。采用包含治疗倾向性评分（PS）的 Fine-Gray 风险回归模型来估计 TDF 与 ETV 相关 HCC 发病率的风险；调整的变量包括人口统计学特征、伴随药物使用和基线合并症，以及包括肝移植和药物变更在内的竞争事件。
在 PS 加权后，TDF 组和 ETV 组匹配良好。在随访期间，90 名患者发生 HCC，包括 50 名接受 ETV 治疗和 40 名接受 TDF 治疗，粗发病率分别为 0.62/100 人年（PY）和 0.30/100 PY。在 PS 加权多变量分析中，与 ETV 相比，TDF 与 HCC 的亚分布风险比为 0.58（95%置信区间 [CI]：0.38-0.89）。当分别分析≥40 岁的患者和男性和女性时，结果相似。
在美国，商业保险覆盖的初治慢性乙型肝炎患者中，与 ETV 相比，TDF 治疗与 HCC 风险显著降低相关。
