Abstract
Background/AimsHypothyroidism 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 MethodsWe 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.ResultsA 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.ConclusionHypothyroidism is associated with poorer overall and recurrence‐free survival of HCC patients receiving liver transplantation. These results require validation.
Highlights
Hepatocellular carcinoma (HCC) is the major form of primary liver cancer, which is the sixth most common cancer and the second leading cause of cancer‐related death globally.[1]
We identified an additional 30 patients with an equivocal diagnosis of hypothyroidism Figure S1; of these, 24 patients had a single abnormal thyroid‐ stimulating hormone (TSH) measurement greater than 5 mIU/L prior to liver transplantation, two patients were diagnosed with hypothyroidism after HCC diagnosis but before liver transplantation, and four patients were diagnosed with hypothyroidism after liver transplantation
Based on the previous literature and our study objectives, we examined the effects of age, gender, race/ethnicity, cirrhotic status, BMI, comorbidities before the onset of HCC, laboratory results including serum TSH, serum AFP, neutrophil to lymphocyte ratio (NLR), Child‐Turcotte‐Pugh (CTP) score, model for end‐stage liver disease (MELD) score before liver transplantation, and tumor characteristics from the explanted liver pathology on overall survival (OS) and recurrence‐free survival (RFS) by univariate Cox regression analysis
Summary
Hepatocellular carcinoma (HCC) is the major form of primary liver cancer, which is the sixth most common cancer and the second leading cause of cancer‐related death globally.[1]. It was reported to be associated with a higher incidence of breast cancer and prostate cancer[4,5] and as a side effect among patients with neck cancer, breast cancer and renal cancer receiving radiotherapy or molecular‐ targeted therapy.[6,7] the development of secondary hypothyroidism was observed to be associated with better survival.[8,9,10,11,12] In HCC patients, we have previously found hypothyroidism to be significantly more prevalent in patients with HCC of unknown etiology.[13] Another study showed that hypothyroidism was associated with a 2.8‐fold higher risk of incidence of HCC in women.[14] An animal study suggested that hypothyroid status favored the onset and progression of pre‐neoplastic lesions to HCC.[15] it is still not clear how hypothyroidism affects the prognosis of HCC patients In this retrospective study, we aimed to investigate the influence of hypothyroidism diagnosed before the onset of HCC on patient outcomes after liver transplantation
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