CRC 'A. M. and A. Migliavacca' Center for the Study of Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
Division of Hepatology, Ospedale San Giuseppe, Università degli Studi di Milano, Milan, Italy.
Liver Int. 2019 Oct;39(10):1964-1974. doi: 10.1111/liv.14197. Epub 2019 Aug 12.
BACKGROUND & AIMS: In Caucasian patients with compensated cirrhosis caused by hepatitis B virus (HBV), the risk of hepatocellular carcinoma (HCC) developing persist despite long-term nucleos(t)ide analogs (NUC) treatment. In the surveillance of this population with persistently normal transaminases because of NUCs, the added value of serum alpha-foetoprotein (AFP) monitoring is poorly defined.
Two hundred and fifty-eight Caucasian HCC-free patients with HBV-compensated cirrhosis who started tenofovir or entecavir while having normal serum AFP levels (≤7 ng/mL) at baseline or within the first year of treatment underwent HCC surveillance by semiannual ultrasound evaluation and serum AFP determination.
During 96 (18-120) months of antiviral therapy, 3947 AFP values were collected, median AFP level was 2 ng/mL. Thirty-five patients developed an HCC at an overall 8-year crude cumulative incidence of 14% (annual incidence of 2%). HCC incidence increased in parallel with increasing AFP thresholds: 24%, 36%, 64% and 92% for AFP levels after exceeding 2, 4, 6 and 7 ng/mL for the first-time. Of the 12 patients who experienced an AFP rise > 7 ng/mL, 11 developed an HCC and one had liver metastases of lung cancer. Overall, an AFP > 7 ng/mL had 99.6% specificity, 31.4% sensitivity, 91.7% PPV, 90.2% NPV, LR+ 70.1 and LR- 0.69 for HCC; this excellent specificity was maintained up to 18 months before HCC detection.
In Caucasian patients with HBV-compensated cirrhosis on long-term NUC, an increase in AFP over 7 ng/mL shows excellent specificity, heralding HCC development within 1 year.
在乙型肝炎病毒（HBV）所致代偿性肝硬化的白种人群中，尽管长期接受核苷（酸）类似物（NUC）治疗，但仍存在发生肝细胞癌（HCC）的风险。在因 NUC 而转氨酶持续正常的这部分人群中，监测血清甲胎蛋白（AFP）的增值意义尚不清楚。
258 例 HBV 代偿性肝硬化、无 HCC 的白种人患者，在基线或治疗的首年内 AFP 水平正常（≤7ng/mL）时开始使用替诺福韦或恩替卡韦，每 6 个月进行一次 HCC 监测，包括半年一次的超声评估和血清 AFP 检测。
在抗病毒治疗的 96（18-120）个月期间，共采集了 3947 次 AFP 值，中位 AFP 水平为 2ng/mL。35 例患者发生 HCC，总体 8 年累积粗发生率为 14%（年发生率为 2%）。随着 AFP 界值的升高，HCC 发生率呈平行增加：首次超过 2、4、6 和 7ng/mL 时，AFP 水平分别为 24%、36%、64%和 92%。12 例 AFP 升高>7ng/mL 的患者中，11 例发生 HCC，1 例发生肺癌肝转移。总的来说，AFP>7ng/mL 对 HCC 的特异性为 99.6%、敏感性为 31.4%、PPV 为 91.7%、NPV 为 90.2%、LR+为 70.1、LR-为 0.69；这种极好的特异性在 HCC 检测前 18 个月内仍保持不变。
在长期接受 NUC 治疗的 HBV 代偿性肝硬化的白种人群中，AFP 升高超过 7ng/mL 具有极好的特异性，预示着 HCC 在 1 年内发生。
