■肝癌风险测试算法(LCR1-LCR2)是一种多分析物血液测试,结合了参与肝细胞修复的蛋白质(载脂蛋白A1和触珠蛋白),已知肝细胞癌(HCC)危险因素(性别,年龄,和γ-谷氨酰转移酶),纤维化标志物(α2-巨球蛋白)和甲胎蛋白(AFP),肝癌的特异性标志物。目的是在接受或未接受抗病毒药物治疗的慢性HCV(CHC)患者中外部验证LCR1-LCR2。
■纳入前的患者来自Hegather队列,法国成人CHC患者的多中心前瞻性研究。LCR1-LCR2在具有测试成分和AFP的患者中进行回顾性评估,在基线可用。共同主要研究结果是根据预定的LCR1-LCR2截止值,LCR1-LCR2对5年HCC发生和无HCC生存的阴性预测值(NPV)。根据风险协变量和对HCV治疗的反应调整了截止值,并使用时间依赖性比例风险模型进行量化。
■总共,4903名患者,1,026(21.9%)与基线肝硬化,包括在研究中。随访患者的中位数为5.7年(IQR4.2-11.3)。共有3,788/4,903(77.3%)患者具有持续的病毒学应答。5年有137例HCC,随访结束时214例。与高风险LCR1-LCR2的113/1,148例患者相比,低风险LCR1-LCR2的24/3,755例患者在5年发生HCC。NPV为99.4%(95%CI99.1-99.6)。类似的发现(危险比,10.8;95%CI,8.1-14.3;p<0.001)在校正暴露于抗病毒药物后获得,年龄,性别,地理起源,HCV基因型3,饮酒,和2型糖尿病。
■结果表明,LCR1-LCR2可用于成功识别5年时HCC风险极低的HCV患者。
肝细胞癌(HCC)是全球癌症相关死亡的第四大原因,也是许多国家增长最快的癌症死亡原因。我们构建并内部验证了一种新的多分析物血液测试来评估这种肝癌风险(LCR1-LCR2)。这项研究证实了LCR1-LCR2在法国国家队列中慢性HCV患者中的表现,以及它在5年内识别肝癌风险非常低的患者的能力。
■该研究已在ClinicalTrials.gov(NCT01953458)注册。
OBJECTIVE: The Liver Cancer Risk test algorithm (LCR1-LCR2) is a multianalyte blood test combining proteins involved in liver cell repair (apolipoprotein-A1 and haptoglobin), known hepatocellular carcinoma (HCC) risk factors (sex, age, and gamma-glutamyl transferase), a marker of fibrosis (alpha2-macroglobulin) and alpha-fetoprotein (AFP), a specific marker of HCC. The aim was to externally validate the LCR1-LCR2 in patients with chronic HCV (CHC) treated or not with antivirals.
METHODS: Pre-included patients were from the Hepather cohort, a multicentre prospective study in adult patients with CHC in France. LCR1-LCR2 was assessed retrospectively in patients with the test components and AFP, available at baseline. The co-primary study outcome was the negative predictive value (NPV) of LCR1-LCR2 for the occurrence of HCC at 5 years and for survival without HCC according to the predetermined LCR1-LCR2 cut-offs. The cut-offs were adjusted for risk covariables and for the response to HCV treatment, and were quantified using time-dependent proportional hazards models.
RESULTS: In total, 4,903 patients, 1,026 (21.9%) with baseline cirrhosis, were included in the study. Patients were followed for a median of 5.7 (IQR 4.2-11.3) years. A total of 3,788/4,903 (77.3%) patients had a sustained virological response. There were 137 cases of HCC at 5 years and 214 at the end of follow-up. HCC occurred at 5 years in 24/3,755 patients with low-risk LCR1-LCR2 compared with 113/1,148 patients with high-risk LCR1-LCR2. The NPV was 99.4% (95% CI 99.1-99.6). Similar findings (hazard ratio, 10.8; 95% CI, 8.1-14.3; p <0.001) were obtained after adjustment for exposure to antivirals, age, sex, geographical origin, HCV genotype 3, alcohol consumption, and type 2 diabetes mellitus.
CONCLUSIONS: The results showed that LCR1-LCR2 can be used to successfully identify patients with HCV at very low risk of HCC at 5 years.
BACKGROUND: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide and the fastest growing cause of cancer death in many countries. We constructed and internally validated a new multianalyte blood test to assess this Liver Cancer Risk (LCR1-LCR2). This study confirmed the performance of LCR1-LCR2 in patients with chronic HCV in the national French cohort Hepather, and its ability to identify patients at a very low risk of HCC at 5 years.
BACKGROUND: The study is registered at ClinicalTrials.gov (NCT01953458).