Modeling the time-related fluctuations of AFP and PIVKA-II serum levels in patients with cirrhosis undergoing surveillance for hepatocellular carcinoma

被引:25
|
作者
Ricco, Gabriele [1 ,2 ,9 ]
Cosma, Chiara [3 ]
Bedogni, Giorgio [4 ]
Biasiolo, Alessandra [5 ]
Guarino, Maria [6 ]
Pontisso, Patrizia [5 ]
Morisco, Filomena [6 ]
Oliveri, Filippo [1 ,2 ]
Cavallone, Daniela [1 ,2 ]
Bonino, Ferruccio [4 ,7 ,8 ]
Plebani, Mario [3 ]
Brunetto, Maurizia Rossana [1 ,2 ,7 ,9 ]
机构
[1] Univ Hosp Pisa, Reference Ctr Tuscany Reg Chron Liver Dis & Canc, Hepatol Unit, Via Paradisa 2, I-56124 Pisa, Italy
[2] Univ Hosp Pisa, Reference Ctr Tuscany Reg Chron Liver Dis & Canc, Lab Mol Genet & Pathol Hepatitis Viruses, Via Paradisa 2, I-56124 Pisa, Italy
[3] Univ Hosp Padua, Dept Lab Med, Padua, Italy
[4] Italian Liver Fdn, FIF, Trieste, Italy
[5] Univ Padua, Dept Med, Padua, Italy
[6] Univ Naples Federico II, Dept Clin Med & Surg, Gastroenterol Unit, Naples, Italy
[7] CNR, Inst Biostruct & Bioimaging, Naples, Italy
[8] Univ Pittsburgh, Med Ctr, Inst Hlth, Siena, Italy
[9] Univ Pisa, Dept Clin & Expt Med, Internal Med, Pisa, Italy
关键词
AFP; biomarkers; cirrhosis; hepatocellular carcinoma; PIVKA-II; surveillance; GAMMA-CARBOXY PROTHROMBIN; ALPHA-FETOPROTEIN; LIVER-CANCER;
D O I
10.3233/CBM-190118
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND: The time-related variability of HCC biomarkers has not been investigated so far. OBJECTIVE: To assess the changes of alpha-fetoprotein (AFP) and protein induced by vitamin-K absence/antagonist-II (PIVKA-II) in patients with HCC (HCC+) as compared to patients without HCC (HCC-). METHODS: AFP and PIVKA-II were measured by a single laboratory using an automated chemiluminescent-enzyme-immunoassay (Fujirebio Inc., Tokyo, Japan) in 1163 sera of 418 cirrhotics (31.1% HBV, 58.6% HCV, 10.3% non-viral etiology) undergoing ultrasound HCC surveillance. The mean (range) number of effective time-points available for analysis was 2.8 (2.0 to 3.0); 124 patients with HCC were matched with 294 who remained HCC free for at least 12 months after the last specimen. AFP and PIVKA-II changes were estimated over time by means of a random-effect generalized least squares (RE-GLS) regression model under the missingness at random assumption. RESULTS: Patients with and without HCC had comparable chronic liver disease etiology and staging. AFP/PIVKA-II median (25th; 75th percentile) values at the latest time-point were 4.2 (2.6; 8.6) ng/mL/32 (25; 42) mAU/mL in HCC- and 8.4 (4.4; 32.1) ng/mL/66 (32; 192) mAU/mL in HCC+ (p< 0.001). Log10AFP and log10PIVKA-II time-changes differed in HCC+ and HCC- patients. In HCC+ patients, both log10AFP and log10PIVKA-II showed an increasing trend over time. In HCC- patients, log10PIVKA-II variations were minimal as compared to log10AFP variations. The percent increase of log10AFP at 6 months vs. baseline was 11% (95%CI 5 to 17%) and 5% (95%CI 1 to 8%) for log10PIVKA-II in HCC+vs. HCC- patients. CONCLUSIONS: The present retrospective study of the biological variability of AFP and PIVKA-II suggests that their time-related changes may serve as potential predictors of HCC. This topic needs to be addressed by longitudinal studies.
引用
收藏
页码:189 / 196
页数:8
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