Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, 23298-0341, USA.
Am J Gastroenterol. 2012 Jan;107(1):64-74. doi: 10.1038/ajg.2011.312. Epub 2011 Sep 20.
Prospective studies of serum hepatocellular carcinoma (HCC) biomarkers in patients with advanced hepatitis C are lacking. The aim of this study was to determine the frequencies and performance of elevated α-fetoprotein (AFP), AFP-L3, and des-γ-carboxy prothrombin (DCP) levels as HCC biomarkers in advanced hepatitis C.
Patients in the HALT-C Trial were tested every 3 months for 42 months. Screening ultrasound was performed every 12 months. Levels of biomarkers were compared in patients in whom HCC did or did not develop.
In all, 855 patients were evaluated; HCC developed in 46. Among patients without HCC, 73.2% had AFP consistently <20, 24.5% had at least one AFP between 20 and 199, and 2.3% had at least one AFP value ≥200 ng/ml; 73.7% had DCP consistently <90, 11.6% had at least one DCP between 90 and 149, and 14.7% had at least one DCP value ≥150 mAU/ml. AFP-L3 ≥10% was present at least once in 9.0% and in 17.1% of those with AFP ≥20 ng/ml. Among all patients with elevated biomarkers, a diagnosis of HCC was made in 0-31.6% (depending on the biomarker and cutoff) during the subsequent 24 months. AFP ≥200 ng/ml had the highest specificity (99%), but sensitivity was ≤20%. DCP ≥40 mAU/ml had the highest sensitivity (76%), but specificity was ≤58%. Independent predictors of elevated AFP were gender (female), race (Black), more advanced disease, and HCC. Elevated DCP was associated with more advanced disease and HCC.
Mild-moderate elevations in total AFP and DCP but not in AFP-L3 occur frequently in patients with chronic hepatitis C and advanced fibrosis, are related to factors other than HCC, and are poor predictors of HCC.
缺乏关于晚期丙型肝炎患者血清肝细胞癌（HCC）生物标志物的前瞻性研究。本研究旨在确定在晚期丙型肝炎患者中，升高的甲胎蛋白（AFP）、AFP-L3 和去γ-羧基凝血酶原（DCP）水平作为 HCC 生物标志物的频率和性能。
HALT-C 试验中的患者在 42 个月内每 3 个月接受一次检测。筛查超声每 12 个月进行一次。比较 HCC 发生和未发生的患者的生物标志物水平。
共有 855 名患者接受评估；其中 46 名患者发生 HCC。在没有 HCC 的患者中，73.2%的 AFP 持续<20ng/ml，24.5%的 AFP 至少有一次在 20 至 199ng/ml 之间，2.3%的 AFP 值至少有一次≥200ng/ml；73.7%的 DCP 持续<90mAU/ml，11.6%的 DCP 至少有一次在 90 至 149mAU/ml 之间，14.7%的 DCP 值至少有一次≥150mAU/ml。AFP-L3≥10%至少出现过一次，在 AFP≥20ng/ml 的患者中占 9.0%和 17.1%。在所有升高生物标志物的患者中，在随后的 24 个月中，HCC 的诊断率为 0-31.6%（取决于生物标志物和截定点）。AFP≥200ng/ml 的特异性最高（99%），但敏感性≤20%。DCP≥40mAU/ml 的敏感性最高（76%），但特异性≤58%。升高 AFP 的独立预测因素是性别（女性）、种族（黑人）、更晚期的疾病和 HCC。升高的 DCP 与更晚期的疾病和 HCC 有关。
在慢性丙型肝炎和晚期纤维化患者中，总 AFP 和 DCP 轻度至中度升高但 AFP-L3 升高不常见，与 HCC 以外的因素有关，是 HCC 的预测指标较差。
