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Background <p>Atezolizumab plus bevacizumab (Ate/Bev) is the first-line systemic therapy for unresectable hepatocellular carcinoma (HCC). However, the prognostic impact of immune-related thyroid adverse events (irTAEs), particularly non-thyroidal illness syndrome (NTIS), remains unclear.</p> Methods <p>We retrospectively analyzed 70 patients with unresectable HCC treated with Ate/Bev. Thyroid function was monitored at baseline and during the treatment. IrTAEs were classified as NTIS (low T3 and/or free T4 with normal or low TSH levels) or thyroid adverse events (hypothyroidism or thyrotoxicosis). Clinical outcomes, including progression-free survival (PFS) and overall survival (OS), were assessed using Kaplan–Meier and Cox regression analysis. Subgroup analyses were performed to examine the associations between liver function, nutritional status, and HCC etiology.</p> Results <p>Among 70 patients (median age, 64&#xa0;years; 80% male), 24 (34.3%) developed irTAEs: 11 had NTIS and 13 had thyroid AEs. NTIS was independently associated with worse OS (adjusted hazard ratio [HR], 2.51; <i>P</i> = 0.041) and shorter median OS (5.4&#xa0;months). In contrast, thyroid AEs were associated with a favorable trend in PFS (adjusted HR, 0.37; <i>P</i> = 0.073) and a higher objective response rate (53.8% vs. 9.1%; <i>P</i> = 0.006). NTIS was correlated with deterioration in albumin level, body mass index, and ALBI grade. Viral HCC was associated with fewer thyroid AEs, while alcohol-related HCC trended toward NTIS.</p> Conclusions <p>Thyroid dysfunction during Ate/Bev therapy is prognostically significant. NTIS reflects systemic deterioration and portends poor survival, whereas thyroid AEs may suggest favorable immune activation. Routine monitoring of thyroid function may aid in risk stratification.</p>

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Non-thyroidal illness syndrome predicts poor prognosis in hepatocellular carcinoma patients treated with atezolizumab and bevacizumab

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月27日

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  • I.-Wen Chen,
  • Cheng-Wei Lin,
  • Po-Ting Lin,
  • Wei Teng,
  • Chung-Wei Su,
  • Tsung-Han Wu,
  • Yi-Chung Hsieh,
  • Wei-Ting Chen,
  • Chen-Chun Lin,
  • Shi-Ming Lin,
  • Chun-Yen Lin

摘要

Background

Atezolizumab plus bevacizumab (Ate/Bev) is the first-line systemic therapy for unresectable hepatocellular carcinoma (HCC). However, the prognostic impact of immune-related thyroid adverse events (irTAEs), particularly non-thyroidal illness syndrome (NTIS), remains unclear.

Methods

We retrospectively analyzed 70 patients with unresectable HCC treated with Ate/Bev. Thyroid function was monitored at baseline and during the treatment. IrTAEs were classified as NTIS (low T3 and/or free T4 with normal or low TSH levels) or thyroid adverse events (hypothyroidism or thyrotoxicosis). Clinical outcomes, including progression-free survival (PFS) and overall survival (OS), were assessed using Kaplan–Meier and Cox regression analysis. Subgroup analyses were performed to examine the associations between liver function, nutritional status, and HCC etiology.

Results

Among 70 patients (median age, 64 years; 80% male), 24 (34.3%) developed irTAEs: 11 had NTIS and 13 had thyroid AEs. NTIS was independently associated with worse OS (adjusted hazard ratio [HR], 2.51; P = 0.041) and shorter median OS (5.4 months). In contrast, thyroid AEs were associated with a favorable trend in PFS (adjusted HR, 0.37; P = 0.073) and a higher objective response rate (53.8% vs. 9.1%; P = 0.006). NTIS was correlated with deterioration in albumin level, body mass index, and ALBI grade. Viral HCC was associated with fewer thyroid AEs, while alcohol-related HCC trended toward NTIS.

Conclusions

Thyroid dysfunction during Ate/Bev therapy is prognostically significant. NTIS reflects systemic deterioration and portends poor survival, whereas thyroid AEs may suggest favorable immune activation. Routine monitoring of thyroid function may aid in risk stratification.