Early antiviral treatment with tenofovir alafenamide to prevent serious clinical adverse events in adults with chronic hepatitis B and moderate or high viraemia (ATTENTION): interim results from a randomised controlled trial.

We aimed to assess the efficacy of early antiviral treatment in preventing serious liver-related adverse events in individuals with non-cirrhotic chronic hepatitis B and moderate or high viraemia but normal or mildly elevated ALT concentrations.

我们的目标是评估早期抗病毒治疗在预防非肝硬化慢性乙型肝炎患者出现严重肝相关不良事件方面的有效性，这些患者虽有中度或高度病毒血症，但ALT浓度正常或轻度升高。

Methods

ATTENTION is an ongoing randomised controlled trialbeing conducted at 22 centres in South Korea and Taiwan.

ATTENTION 是一项正在进行的随机对照试验，正在韩国和台湾的 22 个中心进行。

Adults aged 40-80 years with non-cirrhotic chronic hepatitis B and serum hepatitis B virus (HBV) DNA concentrations between 4 log10 IU/mL and 8 log10 IU/mL, and ALT concentrations lower than 70 U/L for males and 50 U/L for females were recruited and randomly assigned (1:1) to receive either oral tenofovir alafenamide (25 mg daily) or no antiviral treatment (observation).

招募了年龄在 40-80 岁之间的成年慢性乙型肝炎患者，这些患者的血清乙型肝炎病毒（HBV）DNA 浓度在 4 log10 IU/mL 和 8 log10 IU/mL 之间，且男性 ALT 浓度低于 70 U/L，女性低于 50 U/L，然后按 1:1 的比例随机分配接受口服替诺福韦阿拉芬胺（每日 25 毫克）或不接受抗病毒治疗（观察）。

The primary endpoint was a composite of hepatocellular carcinoma, hepatic decompensation (eg, development of portal hypertensive complications including ascites, gastro-oesophageal varices, or Child-Pugh score of ≥7), liver transplantation, or death from any cause, analysed in the intention-to-treatpopulation.

主要终点是肝细胞癌、肝功能失代偿（例如，门静脉高压并发症的发展，包括腹水、胃食管静脉曲张或Child-Pugh评分≥7）、肝移植或任何原因导致的死亡的复合终点，分析在意向治疗人群中进行。

The safety population comprised all randomly assigned participants who received at least one dose of the study treatment.

安全性人群包括所有随机分配的参与者，他们至少接受了研究治疗的一剂。

This interim analysis was prespecified at 4 years after enrolment of the first participant.

本中期分析是在首位参与者入组后的4年预先设定的。

This study is registered with ClinicalTrials.gov, NCT03753074.

该研究已在ClinicalTrials.gov注册，注册号为NCT03753074。

Results

Between Feb 8, 2019 and Oct 17, 2023 (the cutoff date for the first interim analysis), 798 individuals were screened and 734 were randomly assigned (369 to tenofovir alafenamide and 365 to observation).

在2019年2月8日至2023年10月17日（第一次中期分析的截止日期）期间，共有798名个体接受了筛查，其中734名被随机分配（369名接受替诺福韦阿拉芬酰胺治疗，365名接受观察）。

At a median follow-up of 17·7 months (IQR 8·3-24·4), the primary endpoint occurred in 11 participants: two in the tenofovir alafenamide group (both hepatocellular carcinoma) and nine in the observation group (seven hepatocellular carcinoma, one hepatic decompensation, and one death), corresponding to an incidencerate of 0·33 per 100 person-years in the tenofovir alafenamide group and 1·57 per 100 person-years in the observation group (hazard ratio0·21 [97·5% CI 0·04-1·20]; p=0·027).

在中位随访时间为17.7个月（四分位数范围8.3-24.4）时，主要终点事件发生在11名参与者中：替诺福韦阿拉芬酰胺组有2例（均为肝细胞癌），观察组有9例（7例肝细胞癌，1例肝功能失代偿，1例死亡），对应于替诺福韦阿拉芬酰胺组的发病率为每100人年0.33例，观察组为每100人年1.57例（风险比0.21 [97.5%置信区间0.04-1.20]；p=0.027）。

The difference between the two groups did not surpass the prespecified boundaries required to stop the trial early.

两组之间的差异没有超过预先设定的早期终止试验的界限。

Serious adverse events, excluding primary endpoints, were reported in 23 (6%) participants in the tenofovir alafenamide group and 24 (7%) in the observation group.

在替诺福韦阿仑酸酯组中有23名（6%）参与者报告了严重的不良事件，排除主要终点事件，在观察组中有24名（7%）参与者报告了严重的不良事件。

interpretation

The results of this interim analysis suggest that early treatment with tenofovir alafenamide reduces the risk of liver-related serious adverse events compared with observation in adults with non-cirrhotic chronic hepatitis B and moderate or high viraemia but normal or mildly elevated ALT concentrations.

这项中期分析表明，与观察相比，早期使用替诺福韦阿仑酸治疗非肝硬化慢性乙型肝炎且病毒载量中等或高但ALT浓度正常或轻度升高的成人，可以降低肝脏相关严重不良事件的风险。

Although these findings await confirmation in planned future analyses, they suggest that existing guidelines could be expanded to allow early antiviral therapy in patients with a moderate or high HBV viral load, irrespective of ALT concentrations.

尽管这些发现需要在未来的计划分析中得到确认，但它们表明现有的指南可以扩展，允许病毒载量中等或高的乙型肝炎病毒（HBV）患者，无论ALT浓度如何，都可以进行早期抗病毒治疗。

funding

Government of South Korea and Gilead Sciences.

韩国政府和吉利德科学公司。