Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.
Hepatology. 2014 Mar;59(3):986-95. doi: 10.1002/hep.26739. Epub 2014 Jan 30.
Alpha-fetoprotein (AFP) is the most widely used biomarker for hepatocellular carcinoma (HCC) surveillance, which is criticized as neither sensitive nor specific in active hepatitis and liver cirrhosis. The aim of this study was to determine the performance of AFP as a tumor marker for HCC in entecavir-treated patients with chronic hepatitis B (CHB). This was a retrospective-prospective cohort study of 1,531 entecavir-treated patients under regular HCC surveillance with AFP and ultrasonography. Mean age was 52 ± 12 years; 1,099 (72%) patients were male and 332 (21.7%) had clinical evidence of cirrhosis. At a mean follow-up of 51 ± 13 months, 57 (2.9%) patients developed HCC (median size: 3.3 cm). AFP fluctuated with alanine aminotransferase (ALT) and peaked at the time of starting entecavir, then gradually decreased after. AFP started to increase 6 months before the diagnosis of HCC. The receiver operator characteristic curve (AUROC) of AFP was highest at the time of HCC diagnosis (0.85; 95% confidence interval [CI]: 0.73-0.98) and remained satisfactory at 3 (0.82; 95% CI: 0.73-0.91) and 6 months (0.79; 95% CI: 0.69-0.89) before the diagnosis. Using the conventional AFP cut-off (20 μg/L) at month 0, the sensitivity and specificity to diagnose HCC were 38.6% and 98.9%, respectively. Adopting the lower cut-off value (6 μg/L) of AFP level at month 0, sensitivity was increased to 80.7%, whereas specificity was decreased to 80.4%.
On-treatment AFP is a specific tumor marker for HCC in CHB patients receiving entecavir therapy. Adopting a lower cut-off value of AFP level at 6 μg/L would significantly increase the sensitivity for HCC detection.
甲胎蛋白（AFP）是肝细胞癌（HCC）监测中最常用的生物标志物，但在活动性肝炎和肝硬化中，其既不敏感也不特异。本研究旨在确定在接受恩替卡韦治疗的慢性乙型肝炎（CHB）患者中，AFP 作为 HCC 肿瘤标志物的性能。
这是一项回顾性前瞻性队列研究，纳入了 1531 例接受 AFP 和超声检查常规 HCC 监测的接受恩替卡韦治疗的患者。平均年龄为 52 ± 12 岁；1099 例（72%）为男性，332 例（21.7%）有临床肝硬化证据。在平均 51 ± 13 个月的随访中，57 例（2.9%）患者发生 HCC（中位大小：3.3 cm）。AFP 随丙氨酸氨基转移酶（ALT）波动，在开始恩替卡韦时达到峰值，然后逐渐下降。AFP 在 HCC 诊断前 6 个月开始升高。AFP 的受试者工作特征曲线（AUROC）在 HCC 诊断时最高（0.85；95%置信区间[CI]：0.73-0.98），在诊断前 3 个月（0.82；95%CI：0.73-0.91）和 6 个月（0.79；95%CI：0.69-0.89）时仍然令人满意。使用 0 个月时的常规 AFP 截断值（20 μg/L），诊断 HCC 的敏感性和特异性分别为 38.6%和 98.9%。采用 0 个月 AFP 水平的较低截断值（6 μg/L），敏感性增加至 80.7%，但特异性降低至 80.4%。
恩替卡韦治疗中的 AFP 是接受恩替卡韦治疗的 CHB 患者 HCC 的特异性肿瘤标志物。采用 AFP 水平的 6μg/L 较低截断值可显著提高 HCC 检测的敏感性。
