Hepatology. 2018 Aug 28. doi: 10.1002/hep.30233. [Epub ahead of print]
Longitudinal Assessment of Three Serum Biomarkers to Detect Very Early Stage Hepatocellular Carcinoma.
Choi J1, Kim GA2, Han S3, Lee W4, Chun S4, Lim YS1.
1
Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
2
Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
3
Department of Applied Statistics, Gachon University, Seongnam-si, Gyeonggi-do, Republic of Korea.
4
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Abstract
We aimed to determine surveillance performance of alpha-fetoprotein (AFP), lectin-reactive AFP (AFP-L3), des-gamma-carboxy prothrombin (DCP), and their combinations for the early detection of hepatocellular carcinoma (HCC) by using prospectively collected longitudinal samples in patients at risk. Among 689 patients with cirrhosis and/or chronic hepatitis B who participated to four prospective studies, 42 HCC cases were diagnosed, selected, and matched with 168 controls for age, sex, etiology, cirrhosis, and duration of follow-up in a 1:4 ratio. Levels of AFP, AFP-L3, and DCP at the time of HCC diagnosis, month -6, and month -12 were compared between the cases and controls. Of 42 HCC cases, 39 (93%) had cirrhosis, 36 (85.7%) had normal alanine aminotransferase levels, and 31 (73.8%) had very early stage HCC (single <2 cm). AFP and AFP-L3 began to increase from 6 months before diagnosis of HCC in the cases (P<0.05), while they remained unchanged in the controls. At HCC diagnosis, the area under the receiver operator characteristic curves (AUROCs) for AFP, AFP-L3, and DCP were 0.77, 0.73, and 0.71, respectively. Combining AFP and AFP-L3 showed higher AUROC (0.83), while adding DCP did not further improve AUROC (0.86). With the optimal cutoff values (AFP, 5 ng/mL and AFP-L3, 4%), sensitivity and specificity of AFP and AFP-L3 combination were 79% and 87%, respectively. The sensitivity of ultrasonography was 48.6%, which was increased to 88.6% and 94.3% by adding AFP and AFP + AFP-L3, respectively.
CONCLUSION:
Among 3 biomarkers, AFP showed the best performance in discriminating HCC cases from controls. AFP and AFP-L3 combination adopting their novel cutoff values (5 ng/mL and 4%, respectively) significantly improved the sensitivity for detecting HCC at very early stage. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
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