Lee Mei-Hsuan, Wu Ping-Feng, Chen Tzu-I, Chan Chi, Lin Hsi-Hsun, Huang Yi-Hsiang, Chen Hsuan-Yu, Lin Yi-Tsung, Chen Chien-Jen
Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Faculty of Medicine, Department of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
JHEP Rep. 2022 Nov 25;5(3):100634. doi: 10.1016/j.jhepr.2022.100634. eCollection 2023 Mar.
BACKGROUND & AIMS: Tenofovir is recommended as part of the first-line antiretroviral therapy (ART) to treat people living with HIV (PLWH) with HBV coinfection. However, the effects of tenofovir-containing ART on hepatocellular carcinoma (HCC) risk among PLWH with/without chronic hepatitis virus infections remain unclear.
This study included 23,838 PLWH. All of them were males aged ≥20 years and followed prospectively during 2000-2017. Four major nationwide registries - the Human Immunodeficiency Virus surveillance database, Taiwan Cancer Registry, Death Certification System, and National Health Insurance Database - were applied to define ART and comorbidities and ascertain newly diagnosed HCC. Tenofovir-containing ART was identified through prescription records. Cox proportional hazards models were used to determine the association of tenofovir use with HCC incidence.
HCC incidence was lower among ever users of tenofovir than among never users (24.2 and 85.7 per 100,000 person-years, respectively). Ever users had significantly reduced HCC risk (adjusted hazard ratio 0.20, 95% CI 0.13-0.31). The effect of tenofovir use on reduced risk for HCC consistently favored never users across many prespecified subgroups, including HBV or HCV coinfection ( <0.05). The findings were consistent in subgroups of PLWH diagnosed with HIV before tenofovir's approval and in those born before the nationwide roll-out of neonatal HBV vaccination.
Our findings underscore the need for randomized controlled trials of tenofovir in combination with long-acting injectable ART regimens to assess its safety and efficacy in PLWH, particularly in those with HBV or HCV coinfection.
Tenofovir's effect on the risk of hepatocellular carcinoma (HCC) among people living with HIV with hepatitis B or C coinfection remains under investigated. This nationwide prospective cohort study, comprising 23,838 men living with HIV, showed that tenofovir-containing antiretroviral therapy was associated with reduced risk of HCC (adjusted relative risk: 0.20, 95% CI 0.13-0.31), which was consistently observed across many prespecified subgroups. The effect of tenofovir use on HCC risk should be further investigated in PLWH, particularly following the development of long-acting injectable ART regimens.
替诺福韦被推荐作为一线抗逆转录病毒疗法（ART）的一部分，用于治疗合并乙型肝炎病毒（HBV）感染的艾滋病病毒（HIV）感染者（PLWH）。然而，含替诺福韦的ART对合并或未合并慢性肝炎病毒感染的PLWH患肝细胞癌（HCC）风险的影响仍不明确。
本研究纳入了23838例PLWH。他们均为年龄≥20岁的男性，并在2000年至2017年期间进行前瞻性随访。应用四个主要的全国性登记系统——人类免疫缺陷病毒监测数据库、台湾癌症登记系统、死亡证明系统和国民健康保险数据库——来定义ART和合并症，并确定新诊断的HCC。通过处方记录确定含替诺福韦的ART。采用Cox比例风险模型来确定使用替诺福韦与HCC发病率之间的关联。
曾使用替诺福韦者的HCC发病率低于从未使用者（分别为每10万人年24.2例和85.7例）。曾使用者的HCC风险显著降低（调整后风险比为0.20，95%置信区间为0.13 - 0.31）。在许多预先设定的亚组中，包括合并HBV或HCV感染的亚组，使用替诺福韦降低HCC风险的效果始终有利于从未使用者（P<0.05）。在替诺福韦获批前被诊断为HIV的PLWH亚组以及在全国范围内新生儿HBV疫苗接种推广之前出生的亚组中，研究结果一致。
我们的研究结果强调了对替诺福韦与长效注射用ART方案联合进行随机对照试验的必要性，以评估其在PLWH中的安全性和有效性，特别是在合并HBV或HCV感染的患者中。
替诺福韦对合并乙型或丙型肝炎病毒感染的HIV感染者患肝细胞癌（HCC）风险的影响仍在研究中。这项全国性前瞻性队列研究纳入了23838例HIV男性感染者，结果显示含替诺福韦的抗逆转录病毒疗法与降低HCC风险相关（调整后相对风险：0.20，95%置信区间0.13 - 0.31），这在许多预先设定的亚组中均一致观察到。在PLWH中，尤其是在长效注射用ART方案出现后，应进一步研究使用替诺福韦对HCC风险的影响。
