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Article Open Access

Ferritin level prospectively predicts hepatocarcinogenesis in patients with chronic hepatitis B virus infection

  • Authors:
    • Zhenyuan Bian
    • Hie‑Won Hann
    • Zhong Ye
    • Chun Yin
    • Yang Wang
    • Wan Fang
    • Shaogui Wan
    • Chun Wang
    • Kaishan Tao
  • View Affiliations / Copyright

    Affiliations: Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Division of Gastroenterology and Hepatology, Department of Medicine, Liver Disease Prevention Center, Thomas Jefferson University, Philadelphia, PA 19107, USA, Division of Population Science, Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA, State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Institute of Pharmacy, Pharmaceutical College of Henan University, Kaifeng, Henan 475004, P.R. China
    Copyright: © Bian et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3499-3508
    |
    Published online on: July 6, 2018
       https://doi.org/10.3892/ol.2018.9099
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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.
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Copy and paste a formatted citation
Spandidos Publications style
Bian Z, Hann HW, Ye Z, Yin C, Wang Y, Fang W, Wan S, Wang C and Tao K: Ferritin level prospectively predicts hepatocarcinogenesis in patients with chronic hepatitis B virus infection. Oncol Lett 16: 3499-3508, 2018.
APA
Bian, Z., Hann, H., Ye, Z., Yin, C., Wang, Y., Fang, W. ... Tao, K. (2018). Ferritin level prospectively predicts hepatocarcinogenesis in patients with chronic hepatitis B virus infection. Oncology Letters, 16, 3499-3508. https://doi.org/10.3892/ol.2018.9099
MLA
Bian, Z., Hann, H., Ye, Z., Yin, C., Wang, Y., Fang, W., Wan, S., Wang, C., Tao, K."Ferritin level prospectively predicts hepatocarcinogenesis in patients with chronic hepatitis B virus infection". Oncology Letters 16.3 (2018): 3499-3508.
Chicago
Bian, Z., Hann, H., Ye, Z., Yin, C., Wang, Y., Fang, W., Wan, S., Wang, C., Tao, K."Ferritin level prospectively predicts hepatocarcinogenesis in patients with chronic hepatitis B virus infection". Oncology Letters 16, no. 3 (2018): 3499-3508. https://doi.org/10.3892/ol.2018.9099
Copy and paste a formatted citation
x
Spandidos Publications style
Bian Z, Hann HW, Ye Z, Yin C, Wang Y, Fang W, Wan S, Wang C and Tao K: Ferritin level prospectively predicts hepatocarcinogenesis in patients with chronic hepatitis B virus infection. Oncol Lett 16: 3499-3508, 2018.
APA
Bian, Z., Hann, H., Ye, Z., Yin, C., Wang, Y., Fang, W. ... Tao, K. (2018). Ferritin level prospectively predicts hepatocarcinogenesis in patients with chronic hepatitis B virus infection. Oncology Letters, 16, 3499-3508. https://doi.org/10.3892/ol.2018.9099
MLA
Bian, Z., Hann, H., Ye, Z., Yin, C., Wang, Y., Fang, W., Wan, S., Wang, C., Tao, K."Ferritin level prospectively predicts hepatocarcinogenesis in patients with chronic hepatitis B virus infection". Oncology Letters 16.3 (2018): 3499-3508.
Chicago
Bian, Z., Hann, H., Ye, Z., Yin, C., Wang, Y., Fang, W., Wan, S., Wang, C., Tao, K."Ferritin level prospectively predicts hepatocarcinogenesis in patients with chronic hepatitis B virus infection". Oncology Letters 16, no. 3 (2018): 3499-3508. https://doi.org/10.3892/ol.2018.9099
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