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. 2024 May 10:11:1380750.
doi: 10.3389/fmed.2024.1380750. eCollection 2024.

The predictive value of γ-glutamyl transferase to serum albumin ratio in hepatocellular carcinoma patients after liver transplantation

Xing-Yu Luo  1   2   3 , Kai-Wun Chang  1 , Nan Ye  1   3 , Chen-Hao Gao  1   3 , Qing-Bo Zhu  1   3 , Jian-Peng Liu  4 , Xing Zhou  5 , Shu-Sen Zheng  1   4 , Zhe Yang  1   2
Affiliations

The predictive value of γ-glutamyl transferase to serum albumin ratio in hepatocellular carcinoma patients after liver transplantation

Xing-Yu Luo et al. Front Med (Lausanne). .

Abstract

Background: Elevated preoperative γ-glutamyl transferase (GGT) levels or reduced serum albumin levels have been established as negative prognostic factors for patients with hepatocellular carcinoma (HCC) and various other tumors. Nonetheless, the prognostic significance of the GGT to serum albumin ratio (GAR) in liver transplantation (LT) therapy for HCC is still not well-defined.

Methods: A retrospective analysis was conducted on the clinical data of 141 HCC patients who underwent LT at Shulan (Hangzhou) Hospital from June 2017 to November 2020. Using the receiver operating characteristic (ROC) curve, the optimal GAR cutoff value to predict outcomes following LT was assessed. Univariate and multivariate Cox proportional hazards regression analyses were used to identify independent risk factors associated with both overall survival (OS) and recurrence-free survival (RFS).

Results: A GAR value of 2.04 was identified as the optimal cutoff for predicting both OS and RFS, with a sensitivity of 63.2% and a specificity of 74.8%. Among these patients, 80 (56.7%) and 90 (63.8%) met the Milan and the University of California San Francisco (UCSF) criteria, respectively. Univariate Cox regression analysis showed that microvascular invasion (MVI), maximum tumor size (>5 cm), total tumor size (>8 cm), liver cirrhosis, TNM stage (III), and GAR (≥2.04) were significantly associated with both postoperative OS and RFS in patients with HCC (all p < 0.05). Multivariate Cox regression analysis indicated that GAR (≥2.04) was independently linked with RFS and OS.

Conclusion: Pre-transplant GAR ≥2.04 is an independent correlate of prognosis and survival outcomes after LT for HCC and can be used as a prognostic indicator for both mortality and tumor recurrence following LT.

Keywords: gamma-glutamyl transferase to serum albumin ratio; hepatocellular carcinoma; liver transplantation; overall survival; prognosis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) The patient selection flowchart. (B) ROC curve of the GAR value in predicting HCC recurrence after liver transplantation. The area under the ROC curve is 0.713. GAR value 2.04 is considered the best cutoff value; its highest Youden index is 0.38; sensitivity and specificity are 63.2 and 74.8%, respectively.
Figure 2
Figure 2
Comparison of overall patient survival and recurrence-free survival between GAR ≥ 2.04 and <2.04 patients. The patients were divided into two groups according to the pre-transplant GAR cutoff value of 2.04. Recipients in the GAR < 2.04 group presented significantly higher OS rates [p < 0.001 (A)] and RFS rates [p < 0.001 (B)] than those in the GAR ≥ 2.04 group.
Figure 3
Figure 3
OS outcomes of patients were divided according to the Milan and UCSF criteria. The patients were divided into the Milan (A) and UCSF (C) criteria, beyond Milan (B) and UCSF (D) criteria. The OS of the Milan,  UCSF, and GAR < 2.04 groups was comparable with that of the GAR ≥ 2.04 group, and no statistically significant difference was presented [p > 0.05 (A,C)]. Patients in the beyond Milan and UCSF criteria and GAR < 2.04 groups had significantly higher OS than the GAR ≥ 2.04 group [p < 0.05 (B,D)].
Figure 4
Figure 4
RFS outcomes of patients were divided according to the Milan and UCSF criteria. The patients were divided into the Milan (A) and UCSF (C) criteria, beyond Milan (B), and UCSF (D) criteria. The RFS of the Milan or UCSF and GAR < 2.04 groups was comparable with that of the GAR≥2.04 group, and no statistically significant difference was presented [p > 0.05 (A,C)]. Patients in the beyond Milan and UCSF criteria and GAR < 2.04 groups had significantly higher RFS than the GAR ≥ 2.04 group [p < 0.05 (B,D)].
Figure 5
Figure 5
Forest plot comparing independent risk factors affecting OS and RFS after transplantation in HCC patients according to multivariate analysis.
Figure 6
Figure 6
Comparison of the predictive accuracy of GAR and other variables in the derivation cohort (A) OS, overall survival (B) RFS, recurrence-free survival.
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Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by grants from the Major Research Plan of Key Research and Development Project of Zhejiang Province (grant numbers: 2023C03046, 2024C03149), the National Natural Science Foundation of China (92159202), the National Key R&D Program of China (2023YFC2306800), the Research Project of Jinan Microecological Biomedicine Shandong Laboratory (grant numbers: JNL-2022016B, JNL-2022049D), the Natural Science Foundation of Zhejiang Province (Y21H160259), the Major Science and Technology Projects of Hainan Province in 2019 (ZDKJ2019009), and the Fundamental Research Funds for the Central Universities (2022ZFJH003).