Oncol Lett. 2018 Sep;16(3):3499-3508. doi: 10.3892/ol.2018.9099. Epub 2018 Jul 6.
Ferritin level prospectively predicts hepatocarcinogenesis in patients with chronic hepatitis B virus infection.
Bian Z1, Hann HW2, Ye Z3, Yin C4, Wang Y1, Fang W4, Wan S5, Wang C3, Tao K1.
Author information
1
Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
2
Division of Gastroenterology and Hepatology, Department of Medicine, Liver Disease Prevention Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
3
Division of Population Science, Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
4
State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
5
Institute of Pharmacy, Pharmaceutical College of Henan University, Kaifeng, Henan 475004, P.R. China.
Abstract
Previous studies have detected a higher level of ferritin in patients with hepatocellular carcinoma (HCC), but a potential causal association between serum ferritin level and hepatocarcinogenesis remains to be clarified. Using a well-established prospective cohort and longitudinally collected serial blood samples, the association between baseline ferritin levels and HCC risk were evaluated in 1,152 patients infected with hepatitis B virus (HBV), a major risk factor for HCC. The association was assessed by Cox proportional hazards regression model using univariate and multivariate analyses and longitudinal analysis. It was demonstrated that HBV patients who developed HCC had a significantly higher baseline ferritin level than those who remained cancer-free (188.00 vs. 108.00 ng/ml, P<0.0001). The patients with a high ferritin level (≥200 ng/ml) had 2.43-fold increased risk of HCC compared to those with lower ferritin levels [hazard ratio (HR), 2.43; 95% confidence interval, 1.63-3.63]. A significant trend of increasing HRs along with elevated ferritin levels was observed (P for trend <0.0001). The association was still significant after multivariate adjustment. Incorporating ferritin into the α-fetoprotein (AFP) model significantly improved the performance of HCC prediction (the area under the curve from 0.74 to 0.77, P=0.003). Longitudinal analysis showed that the average ferritin level in HBV patients who developed HCC was persistently higher than in those who were cancer-free during follow-up. HCC risk reached a peak at approximately the fifth year after baseline ferritin detection. Moreover, stratified analyses showed that the association was noted in both males and females, and was prominent in patients with a low AFP value. In short, serum ferritin level could independently predict the risk of HBV-related HCC and may have a complementary role in AFP-based HCC diagnosis. Future studies are warranted to validate these findings and test its clinical applicability in HCC prevention and management.
KEYWORDS:
ferritin; hepatitis B virus; hepatocellular carcinoma; prospective; risk
