Yoo Hye-Jin, Kim Jae-Young, Yoo Jeong-Ju, Lee Hye Won, Kim Sang Gyune, Kim Young Seok
Department of Internal Medicine, Soonchunhyang University School of Medicine, Chungcheongnam-do, Republic of Korea.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheonsi Gyeonggido, Republic of Korea.
JHEP Rep. 2024 Nov 12;7(2):101268. doi: 10.1016/j.jhepr.2024.101268. eCollection 2025 Feb.
BACKGROUND & AIMS: Tenofovir alafenamide (TAF) lacks extensive research regarding its impact on hepatocellular carcinoma (HCC). This study evaluated and compared the effects of TAF, tenofovir disoproxil fumarate (TDF), and entecavir (ETV) on HCC incidence using nationwide claim data.
In total, 75,816 patients with treatment-naïve HBV were included in the study and divided into TAF (n = 25,680), TDF (n = 26,954), and ETV (n = 23,182) groups after exclusions. Propensity score matching (1:1:1) resulted in 17,537 patients per group. HCC incidence rates were compared among the groups.
Before matching, the incidence of HCC was significantly lower in the TAF group compared with the TDF and ETV groups (11.47 15.04 and 14.24 per 1,000 person-years). The incidence rate ratio (IRR) for TDF was 1.31 (1.19-1.44) and for ETV was 1.24 (1.12-1.37). Before matching, the TAF group had a significantly lower HCC compared with TDF and ETV in both patients with and without cirrhosis. After matching, the TAF group had a lower HCC incidence compared with the TDF group (12.38 15.39, IRR 1.24, <0.001) but not with ETV group (IRR 1.08, = 0.219). In patients with cirrhosis, TAF had lower HCC incidence compared with TDF and ETV (30.25 39.56 and 38.51, respectively). In patients without cirrhosis, the TAF group had a lower HCC incidence compared with the TDF group (IRR 1.19, = 0.030) but not the ETV group (IRR 0.85, = 0.066). Cox regression analysis showed that the TAF group had a significantly lower HCC incidence compared with the TDF (hazard ratio 1.335, <0.001) and ETV groups (hazard ratio 1.162, = 0.011), after adjusting for age, gender, and cirrhosis status.
The TAF group consistently demonstrated a lower incidence of HCC compared with the TDF and ETV groups, especially in patients with cirrhosis.
This work aimed to fill the knowledge gap regarding the comparative efficacy of tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), and entecavir (ETV) in reducing the incidence of hepatocellular carcinoma (HCC) in patients with chronic HBV. The results are particularly crucial for healthcare providers and policymakers, because they highlight the significantly lower incidence of HCC associated with TAF, especially in patients with cirrhosis. These results suggest TAF as a preferable antiviral therapy option to mitigate HCC risk, thus influencing clinical decision-making and healthcare guidelines. From a practical perspective, these findings can guide physicians in prescribing more effective treatments, assist researchers in designing further studies to explore the mechanisms behind the effectiveness of TAF, and inform policymakers to craft healthcare policies that optimize patient outcomes while considering potential limitations, such as the observational nature of the study and residual confounding factors.
关于替诺福韦艾拉酚胺（TAF）对肝细胞癌（HCC）影响的研究尚不充分。本研究利用全国性医保报销数据评估并比较了TAF、富马酸替诺福韦二吡呋酯（TDF）和恩替卡韦（ETV）对HCC发病率的影响。
本研究共纳入75816例初治慢性乙型肝炎患者，排除部分患者后分为TAF组（n = 25680）、TDF组（n = 26954）和ETV组（n = 23182）。采用倾向评分匹配法（1:1:1），每组最终纳入17537例患者。比较三组患者的HCC发病率。
匹配前，TAF组的HCC发病率显著低于TDF组和ETV组（分别为每1000人年11.47例、15.04例和14.24例）。TDF组的发病率比值比（IRR）为1.31（1.19 - 1.44），ETV组为1.24（1.12 - 1.37）。匹配前，无论有无肝硬化，TAF组的HCC发病率均显著低于TDF组和ETV组。匹配后，TAF组的HCC发病率低于TDF组（分别为每1000人年12.38例、15.39例，IRR 1.24，P < 0.001），但与ETV组无差异（IRR 1.08，P = 0.219）。在肝硬化患者中，TAF组的HCC发病率低于TDF组和ETV组（分别为每1000人年30.25例、39.56例和38.51例）。在无肝硬化患者中，TAF组的HCC发病率低于TDF组（IRR 1.19，P = 0.030），但与ETV组无差异（IRR 0.85，P = 0.066）。Cox回归分析显示，在调整年龄、性别和肝硬化状态后，TAF组的HCC发病率显著低于TDF组（风险比1.335，P < 0.001）和ETV组（风险比1.162，P = 0.011）。
与TDF组和ETV组相比，TAF组的HCC发病率始终较低，尤其是在肝硬化患者中。
本研究旨在填补关于替诺福韦艾拉酚胺（TAF）、富马酸替诺福韦二吡呋酯（TDF）和恩替卡韦（ETV）在降低慢性乙型肝炎患者肝细胞癌（HCC）发病率方面比较疗效的知识空白。研究结果对医疗服务提供者和政策制定者尤为重要，因为它们突出了TAF与显著较低的HCC发病率相关，尤其是在肝硬化患者中。这些结果表明TAF是降低HCC风险的更优抗病毒治疗选择，从而影响临床决策和医疗指南。从实际角度来看，这些发现可以指导医生开具更有效的治疗方案，协助研究人员设计进一步研究以探索TAF有效性背后的机制，并为政策制定者制定优化患者治疗效果的医疗政策提供参考，同时考虑到研究的观察性本质和残余混杂因素等潜在局限性。
