Poynard Thierry, Lacombe Jean Marc, Deckmyn Olivier, Peta Valentina, Akhavan Sepideh, Zoulim Fabien, de Ledinghen Victor, Samuel Didier, Mathurin Philippe, Ratziu Vlad, Thabut Dominique, Housset Chantal, Fontaine Hélène, Pol Stanislas, Carrat Fabrice
Department of Hepato-Gastroenterology, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière Hospital, Paris, France.
INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Sorbonne Université, Paris, France.
Gastro Hep Adv. 2022 May 25;1(4):604-617. doi: 10.1016/j.gastha.2022.02.008. eCollection 2022.
The liver cancer risk test (LCR1-LCR2) is a multianalyte blood test combining proteins involved in liver cell repair (apolipoprotein A1, haptoglobin), hepatocellular carcinoma (HCC) risk factors (gender, age, gamma glutamyl transpeptidase), a marker of fibrosis (alpha2-macroglobulin), and alpha-fetoprotein, a specific marker of HCC. The aim was to externally validate LCR1-LCR2 in hepatitis B.
Preincluded patients were from the Hepather cohort, a multicenter, multiethnic prospective study in 6071 patients. The coprimary study outcome was the negative predictive value of LCR1-LCR2 at 5 years for the occurrence of HCC and survival without HCC according to the predetermined LCR1-LCR2 cutoffs, adjusted for risk covariables and for chronic hepatitis B treatment and quantified using time-dependent Cox proportional hazards models. A post hoc analysis compared the number of patients needed to screen one cancer by LCR1-LCR2 and PAGE-B.
A total of 3520 patients, 191 (5.4%) with cirrhosis, with at least 1 year of follow-up were included. A total of 76 HCCs occurred over a median (interquartile range) of 6.0 years (4.8-7.3) of follow-up. Among the 3367 patients with low-risk LCR1-LCR2, the 5-year negative predictive value was 99.3% (95% confidence interval = 99.0-99.6), with a significant Cox hazard ratio (6.4, 3.1-13.0; < .001) obtained after adjustment for exposure to antivirals, age, gender, geographical origin, HBe-Ag status, alcohol consumption, and type-2 diabetes. LCR1-LCR2 outperformed PAGE-B for number of patients needed to screen mean (95% CI), 8.5 (3.2-8.1) vs 26.3 (17.5-38.5; < .0001), respectively.
The performance of LCR1-LCR2 to identify patients with chronic hepatitis B at very low risk of HCC at 5 years was externally validated. ClinicalTrials.gov: NCT01953458.
肝癌风险检测（LCR1-LCR2）是一种多分析物血液检测，它结合了参与肝细胞修复的蛋白质（载脂蛋白A1、触珠蛋白）、肝细胞癌（HCC）风险因素（性别、年龄、γ-谷氨酰转肽酶）、纤维化标志物（α2-巨球蛋白）以及甲胎蛋白（HCC的特异性标志物）。目的是在乙型肝炎患者中对LCR1-LCR2进行外部验证。
预先纳入的患者来自Hepather队列研究，这是一项针对6071例患者的多中心、多民族前瞻性研究。共同主要研究结局是根据预先设定的LCR1-LCR2临界值，LCR1-LCR2在5年时对HCC发生和无HCC生存的阴性预测值，并针对风险协变量以及慢性乙型肝炎治疗进行调整，使用时间依赖性Cox比例风险模型进行量化。一项事后分析比较了通过LCR1-LCR2和PAGE-B筛查出一例癌症所需的患者数量。
共纳入3520例患者，其中191例（5.4%）有肝硬化，随访时间至少1年。在中位（四分位间距）6.0年（4.8 - 7.3年）的随访期间共发生76例HCC。在3367例LCR1-LCR2低风险患者中，5年阴性预测值为99.3%（95%置信区间 = 99.0 - 99.6），在对抗病毒药物暴露、年龄、性别、地理来源、HBe抗原状态、饮酒情况和2型糖尿病进行调整后，获得显著的Cox风险比（6.4，3.1 - 13.0；P <.001）。LCR1-LCR2在筛查一例癌症所需患者数量方面优于PAGE-B，分别为平均（95% CI）8.5（3.2 - 8.1）例和26.3（17.5 - 38.5；P <.0001）例。
LCR1-LCR2在识别5年时HCC极低风险的慢性乙型肝炎患者方面的性能得到了外部验证。ClinicalTrials.gov：NCT01953458。
