Utility of Serum Biomarkers in Addition to Ultrasound for Early Detection of Hepatocellular Carcinoma in High-Risk Patients: A Randomized Controlled Trial.

Current strategies are suboptimal with many patients presenting with advanced HCC.

当前的策略并不理想，许多患者在出现晚期HCC时才被诊断。

This randomized controlled trialcompared the combined use of serum biomarker (BM) measurements and abdominal ultrasound (US) with US alone for the diagnosis of early-stage HCC.

这项随机对照试验比较了血清生物标志物(BM)测量与腹部超声(US)联合使用与仅使用US在诊断早期肝细胞癌(HCC)中的效果。

Methods

Adults with cirrhosis or high-risk hepatitis B virus (HBV) infection were randomized (1:1) to biannual surveillance with US alone (group A) or US and BMs (group B) in blocks of 2 or 4.

随机将患有肝硬化或高风险乙型肝炎病毒(HBV)感染的成年人（1:1）分为两组，一组每半年进行一次US检查（A组），另一组同时进行US和BMs检查（B组），分组以2或4为单位进行。

Positive US results or elevated BMs (α-fetoprotein [AFP] >100 ng/mL, lectin-reactive fraction of AFP [AFP-L3] >10%, des-gamma-carboxy prothrombin [DCP] >2 ng/mL) triggered further imaging for HCC confirmation.

超声检查结果阳性或肿瘤标志物升高（甲胎蛋白[AFP]>100 ng/mL，AFP的凝集素反应部分[AFP-L3]>10%，去γ-羧基凝血酶原[DCP]>2 ng/mL）会触发进一步的影像学检查以确认肝细胞癌（HCC）的存在。

Primary end point was proportion of early-stage HCCs.

主要终点是早期肝细胞癌（HCC）的比例。

Results

There were 1208 patients randomized (n = 603 group A, n = 605 group B).

共有1208名患者被随机分配（A组603人，B组605人）。

Mean ± SD age was 58.4 ± 9.8 years, 71.8% were male, 55.1% were Asian, 64.0% had HBV, and 64.3% had cirrhosis.

平均年龄为58.4±9.8岁，71.8%为男性，55.1%为亚洲人，64.0%携带乙型肝炎病毒（HBV），64.3%患有肝硬化。

During follow-up, 35 HCCs (5.8%) developed in group A (n = 30 early-stage, n = 5 late-stage) and 27 (4.5%) developed in group B (n = 22 early-stage, n = 5 late-stage).

随访期间，A组（n=30早期，n=5晚期）发展出35例（5.8%）肝细胞癌（HCC），B组（n=22早期，n=5晚期）发展出27例（4.5%）肝细胞癌。

Early-stage HCC incidencewas 1.2 per 100 person-years with cumulative probabilities of 1.3% at 52 weeks and 5.9% at 260 weeks.

早期肝细胞癌的发病率为每100人年1.2例，52周时累积概率为1.3%，260周时累积概率为5.9%。

Early-stage HCC detection rate did not differ by study arm (hazard ratio, 0.81; 95% CI, 0.47-1.40; P = .45).

早期肝细胞癌的检出率在研究组之间没有差异（风险比，0.81；95%置信区间，0.47-1.40；P = .45）。

In group B, elevated AFP-L3 was equally effective compared with using all 3 BMs.

在B组中，甲胎蛋白异质体L3（AFP-L3）升高与使用全部3种肿瘤标志物（BMs）同样有效。

Conclusions

Addition of AFP, AFP-L3, and DCP to biannual US did not improve early-stage HCC detection.

将甲胎蛋白（AFP）、AFP-L3和DCP添加到每半年一次的超声检查中，并未提高早期肝细胞癌（HCC）的检测率。

The trial was not adequately powered to provide evidence that the use of BMs aside from US plus AFP improves HCC surveillance.

该试验的样本量不足以证明除超声检查加甲胎蛋白（AFP）之外，使用其他生物标志物（BMs）能改善肝细胞癌（HCC）的监测。

Establishing and validating alternative approaches to incorporation of BMs may improve surveillance methods for early-stage HCC detection.

建立并验证将骨髓细胞（BMs）纳入的替代方法可能会改善早期肝细胞癌（HCC）检测的监测方法。

clinicaltrials

gov, Number: NCT02272504.

政府机构，编号：NCT02272504。