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Article

PD‑1 inhibitors combined with tyrosine kinase inhibitor‑associated hypothyroidism is a predictive factor for antitumor effectiveness in male patients with hepatocellular carcinoma

  • Authors:
    • Bailu Cao
    • Min Ai
    • Ping Huang
    • Huan Zhong
  • View Affiliations / Copyright

    Affiliations: Department of Hepatology, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine (Nanjing Second Hospital), Nanjing, Jiangsu 210003, P.R. China
  • Article Number: 285
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    Published online on: May 7, 2026
       https://doi.org/10.3892/ol.2026.15641
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Abstract

Tyrosine kinase inhibitors (TKIs) and programmed cell death protein‑1 (PD‑1) inhibitors are well‑established first‑line systemic therapies for hepatocellular carcinoma (HCC), with hypothyroidism as a prominent immune‑related adverse event. However, the female sex is a known risk factor for thyroid dysfunction associated with TKIs. The present study aimed to determine whether PD‑1 inhibitor plus TKIs‑induced hypothyroidism predicts treatment efficacy in male patients with HCC. A retrospective cohort study enrolled 77 male patients with confirmed HCC who received PD‑1 inhibitor‑TKIs combination therapy at Nanjing Second Hospital (Nanjing, China). According to the evaluation of thyroid function, patients were divided into normal thyroid function and hypothyroidism groups, based on serial thyroid function evaluations. The primary endpoint of the present study was progression‑free survival (PFS). Baseline serum thyroid‑­stimulating hormone (TSH) and thyroglobulin antibody (TgAb) levels were significantly higher in the hypothyroidism group compared with the group with normal thyroid function [TSH, 4.2 mIU/l; 95% confidence interval (CI), 2.0‑4.6 mIU/l vs. 1.7 mIU/l (95% CI, 1.2‑3.1 mIU/l); P<0.001; TgAb, 12.4 IU/ml (95% CI, 2.1‑18.2 IU/ml) vs. 1.4 IU/ml (95% CI, 0.8‑5.0 IU/ml); P=0.007]. The group with hypothyroidism had a median PFS of 8.0 months, which was longer compared with the group with normal thyroid function (6.1 months; P<0.001). Cox regression analysis demonstrated that PD‑1 inhibitors plus TKIs‑induced hypothyroidism [hazard ratio (HR)=0.320; 95% CI, 0.160‑0.641; P=0.001] and baseline serum α‑fetoprotein >200 ng/ml (HR=2.354; 95% CI, 1.277‑4.340; P=0.008) were independent prognostic factors of PFS in male patients with HCC. In conclusion, de novo hypothyroidism during PD‑1 inhibitors combined with TKIs is associated with prolonged PFS in male patients with HCC.
View Figures

Figure 1

Antitumor effect between two groups
of male patients with hepatocellular carcinoma. CR, complete
response; PD, progressive disease; PR, partial response; SD, stable
disease.

Figure 2

Comparison of PFS and OS between two
groups of male patients with hepatocellular carcinoma. OS, overall
survival; PFS, progression-free survival; AFP, α-fetoprotein.
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Copy and paste a formatted citation
Spandidos Publications style
Cao B, Ai M, Huang P and Zhong H: PD‑1 inhibitors combined with tyrosine kinase inhibitor‑associated hypothyroidism is a predictive factor for antitumor effectiveness in male patients with hepatocellular carcinoma. Oncol Lett 32: 285, 2026.
APA
Cao, B., Ai, M., Huang, P., & Zhong, H. (2026). PD‑1 inhibitors combined with tyrosine kinase inhibitor‑associated hypothyroidism is a predictive factor for antitumor effectiveness in male patients with hepatocellular carcinoma. Oncology Letters, 32, 285. https://doi.org/10.3892/ol.2026.15641
MLA
Cao, B., Ai, M., Huang, P., Zhong, H."PD‑1 inhibitors combined with tyrosine kinase inhibitor‑associated hypothyroidism is a predictive factor for antitumor effectiveness in male patients with hepatocellular carcinoma". Oncology Letters 32.1 (2026): 285.
Chicago
Cao, B., Ai, M., Huang, P., Zhong, H."PD‑1 inhibitors combined with tyrosine kinase inhibitor‑associated hypothyroidism is a predictive factor for antitumor effectiveness in male patients with hepatocellular carcinoma". Oncology Letters 32, no. 1 (2026): 285. https://doi.org/10.3892/ol.2026.15641
Copy and paste a formatted citation
x
Spandidos Publications style
Cao B, Ai M, Huang P and Zhong H: PD‑1 inhibitors combined with tyrosine kinase inhibitor‑associated hypothyroidism is a predictive factor for antitumor effectiveness in male patients with hepatocellular carcinoma. Oncol Lett 32: 285, 2026.
APA
Cao, B., Ai, M., Huang, P., & Zhong, H. (2026). PD‑1 inhibitors combined with tyrosine kinase inhibitor‑associated hypothyroidism is a predictive factor for antitumor effectiveness in male patients with hepatocellular carcinoma. Oncology Letters, 32, 285. https://doi.org/10.3892/ol.2026.15641
MLA
Cao, B., Ai, M., Huang, P., Zhong, H."PD‑1 inhibitors combined with tyrosine kinase inhibitor‑associated hypothyroidism is a predictive factor for antitumor effectiveness in male patients with hepatocellular carcinoma". Oncology Letters 32.1 (2026): 285.
Chicago
Cao, B., Ai, M., Huang, P., Zhong, H."PD‑1 inhibitors combined with tyrosine kinase inhibitor‑associated hypothyroidism is a predictive factor for antitumor effectiveness in male patients with hepatocellular carcinoma". Oncology Letters 32, no. 1 (2026): 285. https://doi.org/10.3892/ol.2026.15641
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