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 M Malhi, Terry M Therneau, Lewis Rowland Roberts

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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)
JournalCancer Medicine
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Hypothyroidism
Liver Transplantation
Hepatocellular Carcinoma
Survival
Recurrence
Thyrotropin
Hormone Replacement Therapy
Thyroid Hormones
Comorbidity
Transplantation
Confidence Intervals
Incidence

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Hypothyroidism is associated with worse outcomes of hepatocellular carcinoma patients after liver transplantation. / Zhang, Ning; Jin, Weidong; Zhou, Shuangnan; Yang, Ju Dong; Harmsen, William S.; Giama, Nasra H.; Wongjarupong, Nicha; Heimbach, Julie K.; Watt, Kymberly D.; Malhi, Harmeet M; Therneau, Terry M; Roberts, Lewis Rowland.

In: Cancer Medicine, 01.01.2018.

Research output: Contribution to journalArticle

Zhang, Ning ; Jin, Weidong ; Zhou, Shuangnan ; Yang, Ju Dong ; Harmsen, William S. ; Giama, Nasra H. ; Wongjarupong, Nicha ; Heimbach, Julie K. ; Watt, Kymberly D. ; Malhi, Harmeet M ; Therneau, Terry M ; Roberts, Lewis Rowland. / Hypothyroidism is associated with worse outcomes of hepatocellular carcinoma patients after liver transplantation. In: Cancer Medicine. 2018.
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abstract = "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.",
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T1 - Hypothyroidism is associated with worse outcomes of hepatocellular carcinoma patients after liver transplantation

AU - Zhang, Ning

AU - Jin, Weidong

AU - Zhou, Shuangnan

AU - Yang, Ju Dong

AU - Harmsen, William S.

AU - Giama, Nasra H.

AU - Wongjarupong, Nicha

AU - Heimbach, Julie K.

AU - Watt, Kymberly D.

AU - Malhi, Harmeet M

AU - Therneau, Terry M

AU - Roberts, Lewis Rowland

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - hypothyroidism

KW - liver cancer

KW - orthotopic liver transplantation

KW - outcomes

KW - risk factors

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