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25-OH-vitamin D deficiency identifies poor tumor response in hepatocellular carcinoma treated with transarterial chemoembolization

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Abstract

Purpose

Vitamin D is implicated linked to liver cancer and chronic liver diseases, but its association with tumor response in hepatocellular carcinoma (HCC) patients undergoing transarterial chemoembolization (TACE) remains unclear. This study aimed to determine whether vitamin D levels influence tumor response in HCC patients treated with TACE.

Methods

A total of 58 HCC patients undergoing TACE were enrolled in the study. Serum 25-hydroxyvitamin D (25-OHD) levels were determined at baseline and 1 day after TACE using electrochemiluminescence immunoassay. Response to TACE was evaluated after a 4–6 week interval. Univariate and multivariate analyses with Cox regression model were performed to determine the risk factors associated with tumor response. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive performance of baseline 25-OHD levels on tumor response in HCC patients undergoing TACE.

Results

43.1% of HCC patients showed 25-OHD deficiency. Baseline 25-OHD level was associated with liver cirrhosis (P = 0.025), vascular invasion (P = 0.031), Barcelona Clinic Liver Cancer stage (P = 0.002) and an alanine aminotransferase increase after TACE (P = 0.021). Serum 25-OHD level was significantly decreased 1 day after TACE (P = 0.045). Multiple tumor numbers (P = 0.034) and low baseline 25-OHD levels (P = 0.040) were independently correlated with poor tumor response after TACE. ROC curve analysis showed that baseline 25-OHD levels present better predictive performance for OR in those patients, compared with other current clinical test pointers.

Conclusion

Our study suggested that 25-OHD deficiency at baseline is a prognostic indicator for a poor tumor response in hepatocellular carcinoma treated with TACE.

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References

  1. Wu DB, Wang ML, Chen EQ, Tang H. New insights into the role of vitamin D in hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol. 2018;12(3):287–94. https://doi.org/10.1080/17474124.2018.1406307.

    Article  CAS  PubMed  Google Scholar 

  2. Rosen CJ. Clinical practice. Vitamin D insufficiency. N Engl J Med. 2011;364(3):248–54. https://doi.org/10.1056/NEJMcp1009570.

    Article  CAS  PubMed  Google Scholar 

  3. Arteh J, Narra S, Nair S. Prevalence of vitamin D deficiency in chronic liver disease. Dig Dis Sci. 2010;55(9):2624–8. https://doi.org/10.1007/s10620-009-1069-9.

    Article  CAS  PubMed  Google Scholar 

  4. Finkelmeier F, Kronenberger B, Koberle V, Bojunga J, Zeuzem S, Trojan J, et al. Severe 25-hydroxyvitamin D deficiency identifies a poor prognosis in patients with hepatocellular carcinoma—a prospective cohort study. Aliment Pharmacol Ther. 2014;39(10):1204–12. https://doi.org/10.1111/apt.12731.

    Article  CAS  PubMed  Google Scholar 

  5. Fedirko V, Duarte-Salles T, Bamia C, Trichopoulou A, Aleksandrova K, Trichopoulos D, et al. Prediagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations: a nested case–control study. Hepatology. 2014;60(4):1222–30. https://doi.org/10.1002/hep.27079.

    Article  CAS  PubMed  Google Scholar 

  6. Wang JB, Abnet CC, Chen W, Dawsey SM, Fan JH, Yin LY, et al. Association between serum 25(OH) vitamin D, incident liver cancer and chronic liver disease mortality in the Linxian Nutrition Intervention Trials: a nested case–control study. Br J Cancer. 2013;109(7):1997–2004. https://doi.org/10.1038/bjc.2013.546.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lai GY, Wang JB, Weinstein SJ, Parisi D, Horst RL, McGlynn KA, et al. Association of 25-Hydroxyvitamin D with liver cancer incidence and chronic liver disease mortality in finnish male smokers of the ATBC study. Cancer Epidemiol Biomarkers Prev. 2018;27(9):1075–82. https://doi.org/10.1158/1055-9965.EPI-17-0877.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Finn RS, Zhu AX, Farah W, Almasri J, Zaiem F, Prokop LJ, et al. Therapies for advanced stage hepatocellular carcinoma with macrovascular invasion or metastatic disease: a systematic review and meta-analysis. Hepatology. 2018;67(1):422–35. https://doi.org/10.1002/hep.29486.

    Article  CAS  PubMed  Google Scholar 

  9. Sacco R, Tapete G, Simonetti N, Sellitri R, Natali V, Melissari S, et al. Transarterial chemoembolization for the treatment of hepatocellular carcinoma: a review. J Hepatocell Carcinoma. 2017;4:105–10. https://doi.org/10.2147/JHC.S103661.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology. 2005;42(5):1208–36. https://doi.org/10.1002/hep.20933.

    Article  PubMed  Google Scholar 

  11. Zhang Y, Huang G, Wang Y, Liang L, Peng B, Fan W, et al. Is salvage liver resection necessary for initially unresectable hepatocellular carcinoma patients downstaged by transarterial chemoembolization? Ten Years of Experience. Oncologist. 2016;21(12):1442–9. https://doi.org/10.1634/theoncologist.2016-0094.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kim M, Kang TW, Cha DI, Jang KM, Kim YK, Kim SH, et al. Identification of arterial hyper enhancement in CT and MRI in patients with hepatocellular carcinoma: value of unenhanced images. Korean J Radiol. 2019;20(2):236–45. https://doi.org/10.3348/kjr.2018.0339.

    Article  PubMed  Google Scholar 

  13. Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30(1):52–60. https://doi.org/10.1055/s-0030-1247132.

    Article  CAS  PubMed  Google Scholar 

  14. Holick MF. Vitamin D status: measurement, interpretation, and clinical application. Ann Epidemiol. 2009;19(2):73–8. https://doi.org/10.1016/j.annepidem.2007.12.001.

    Article  PubMed  Google Scholar 

  15. Souberbielle JC, Body JJ, Lappe JM, Plebani M, Shoenfeld Y, Wang TJ, et al. Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: recommendations for clinical practice. Autoimmun Rev. 2010;9(11):709–15. https://doi.org/10.1016/j.autrev.2010.06.009.

    Article  CAS  PubMed  Google Scholar 

  16. Dawson-Hughes B, Heaney RP, Holick MF, Lips P, Meunier PJ, Vieth R. Estimates of optimal vitamin D status. Osteoporos Int. 2005;16(7):713–6. https://doi.org/10.1007/s00198-005-1867-7.

    Article  CAS  PubMed  Google Scholar 

  17. Vieth R, Bischoff-Ferrari H, Boucher BJ, Dawson-Hughes B, Garland CF, Heaney RP, et al. The urgent need to recommend an intake of vitamin D that is effective. Am J Clin Nutr. 2007;85(3):649–50. https://doi.org/10.1093/ajcn/85.3.649.

    Article  CAS  PubMed  Google Scholar 

  18. Malham M, Jorgensen SP, Ott P, Agnholt J, Vilstrup H, Borre M, et al. Vitamin D deficiency in cirrhosis relates to liver dysfunction rather than aetiology. World J Gastroenterol. 2011;17(7):922–5. https://doi.org/10.3748/wjg.v17.i7.922.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Vidot H, Potter A, Cheng R, Allman-Farinelli M, Shackel N. Serum 25-hydroxyvitamin D deficiency and hepatic encephalopathy in chronic liver disease. World J Hepatol. 2017;9(10):510–8. https://doi.org/10.4254/wjh.v9.i10.510.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Paternostro R, Wagner D, Reiberger T, Mandorfer M, Schwarzer R, Ferlitsch M, et al. Low 25-OH-vitamin D levels reflect hepatic dysfunction and are associated with mortality in patients with liver cirrhosis. Wien Klin Wochenschr. 2017;129(1–2):8–15. https://doi.org/10.1007/s00508-016-1127-1.

    Article  CAS  PubMed  Google Scholar 

  21. Hibler EA, Hu C, Jurutka PW, Martinez ME, Jacobs ET. Polymorphic variation in the GC and CASR genes and associations with vitamin D metabolite concentration and metachronous colorectal neoplasia. Cancer Epidemiol Biomarkers Prev. 2012;21(2):368–75. https://doi.org/10.1158/1055-9965.EPI-11-0916.

    Article  CAS  PubMed  Google Scholar 

  22. Muindi JR, Adjei AA, Wu ZR, Olson I, Huang H, Groman A, et al. Serum vitamin D metabolites in colorectal cancer patients receiving cholecalciferol supplementation: correlation with polymorphisms in the vitamin D genes. Horm Cancer. 2013;4(4):242–50. https://doi.org/10.1007/s12672-013-0139-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This study was supported by the National Natural Science Foundation of China for Young Scientists (81701799).

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Author notes

  1. Y.-Q. Wu and W.-Z. Fan contributed equally to the study.

Authors and Affiliations

  1. Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan 2 Road, Guangzhou, 510080, People’s Republic of China

    Y.-Q. Wu, W.-Z. Fan, M. Xue, J. Guo, J.-L. Wei, Y. Wang, W. Yao, Y. Zhao & J.-P. Li

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  1. Y.-Q. Wu
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Correspondence to J.-P. Li.

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This manuscript has not been published or presented elsewhere in part or in entirety and is not under consideration by another journal. The authors declare that they have no conflict of interest.

Ethical approval

The study design was approved by the ethics committee at the First Affiliated Hospital of Sun Yat-sen University (NO [2018] 230).

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All study participants provided informed consent.

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Wu, YQ., Fan, WZ., Xue, M. et al. 25-OH-vitamin D deficiency identifies poor tumor response in hepatocellular carcinoma treated with transarterial chemoembolization. Clin Transl Oncol 22, 70–80 (2020). https://doi.org/10.1007/s12094-019-02146-3

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