Hypothyroidism is associated with worse outcomes of hepatocellular carcinoma patients after liver transplantation

Ning Zhang, Weidong Jin, Shuangnan Zhou, Ju Dong Yang, William S. Harmsen, Nasra H. Giama, Nicha Wongjarupong, Julie K. Heimbach, Kymberly D. Watt, Harmeet Malhi, Terry M. Therneau, Lewis R. Roberts

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Background/Aims: Hypothyroidism has been associated with hepatocellular carcinoma (HCC) incidence; however, the relationship between hypothyroidism and HCC patient outcomes is unclear. We investigated the impact of hypothyroidism on outcomes after liver transplantation for HCC. Materials and Methods: We retrospectively studied HCC patients transplanted between January 2000 and December 2015. Hypothyroidism was defined as a thyroid-stimulating hormone (TSH) level continuously greater than 5 mIU/L, a documented history of hypothyroidism, or treatment with thyroid hormone replacement therapy. Multivariate Cox regression was used to assess the impact of hypothyroidism on overall survival (OS) and recurrence-free survival (RFS) adjusting for potential confounders. Subgroup analyses and interaction tests were conducted to compare the impact of hypothyroidism in different subgroups and assess for possible synergistic effects. Sensitivity analyses were performed among different cohorts to verify the stability of the results. Results: A total of 343 HCC patients who underwent liver transplantation were included in the analysis. The primary analysis was conducted among 288 patients diagnosed with HCC prior to transplantation. Hypothyroidism was independently associated with worse OS and RFS, as was elevated TSH. The adjusted hazard ratio (AHR) of hypothyroidism was 2.45 (95% confidence interval [CI], 1.44-4.18) for OS and 5.54 (2.36, 13.01) for RFS. The AHR of TSH for OS was 1.05 (1.02, 1.09) and 1.08 (1.03, 1.13) for RFS. No interaction was found among different subgroups categorized by etiology and comorbidity. The results were stable to sensitivity analyses. Conclusion: Hypothyroidism is associated with poorer overall and recurrence-free survival of HCC patients receiving liver transplantation. These results require validation.

Original languageEnglish (US)
Pages (from-to)5870-5878
Number of pages9
JournalCancer medicine
Issue number12
StatePublished - Dec 2018
Externally publishedYes

Bibliographical note

Funding Information:
This publication was supported by grants CA165076 and CA186566 from the National Cancer Institute (NCI; to LRR). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

Publisher Copyright:
© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Copyright 2019 Elsevier B.V., All rights reserved.


  • hypothyroidism
  • liver cancer
  • orthotopic liver transplantation
  • outcomes
  • risk factors

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