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Tumor recurrence is a life‐threatening complication after liver transplantation (LT) for hepatocellular carcinoma (HCC). Precise recurrence risk stratification before transplantation is essential for the management of recipients. Here, we aimed to establish an inflammation‐related prediction model for posttransplant HCC recurrence based on pretransplant peripheral cytokine profiling. Two hundred and ninety‐three patients who underwent LT in two independent medical centers were enrolled, and their pretransplant plasma samples were sent for cytokine profiling. We identified four independent risk factors, including alpha‐fetoprotein, systemic immune‐inflammation index, interleukin 6, and osteocalcin in the training cohort (n = 190) by COX regression analysis. A prediction model named inflammatory fingerprint (IFP) was established based on the above factors. The IFP effectively predicted posttransplant recurrence (area under the receiver operating characteristic curve [AUROC]: 0.792, C‐index: 0.736). The high IFP group recipients had significantly worse 3‐year recurrence‐free survival rates (37.9 vs. 86.9%, p < 0.001). Simultaneous T‐cell profiling revealed that recipients with high IFP were characterized by impaired T cell function. The IFP also performed well in the validation cohort (n = 103, AUROC: 0.807, C‐index: 0.681). In conclusion, the IFP efficiently predicted posttransplant HCC recurrence and helped to refine pretransplant risk stratification. Impaired T cell function might be the intrinsic mechanism for the high recurrence risk of recipients in the high IFP group. [ABSTRACT FROM AUTHOR]

Objective: Lung metastasis is a common and fatal complication of liver transplantation for hepatocellular carcinoma (HCC). The precise prediction of post-transplant lung metastasis in the early phase is of great value., Methods: The mRNA profiles of primary and paired lung metastatic lesions were analyzed to determine key signaling pathways. We enrolled 241 HCC patients who underwent liver transplantation from three centers. Tissue microarrays were used to evaluate the prognostic capacity of tumor necrosis factor (TNF), tumor necrosis factor receptor 1 (TNFR1), and TNFR2, particularly for post-transplant lung metastasis., Results: Comparison of primary and lung metastatic lesions revealed that the TNF-dependent signaling pathway was related to lung metastasis of HCC. The expression of TNF was degraded in comparison to that in para-tumor tissues (P<0.001). The expression of key receptors in the TNF-dependent signaling pathway, TNFR1 and TNFR2, was higher in HCC tissues than in para-tumor tissues (P<0.001). TNF and TNFR1 showed no relationship with patients' outcomes, whereas elevated TNFR2 in tumor tissue was significantly associated with worse overall survival (OS) and increased recurrence risk (5-year OS rate: 31.9% vs. 62.5%, P<0.001). Notably, elevated TNFR2 levels were also associated with an increased risk of post-transplant lung metastasis (hazard ratio: 1.146; P<0.001). Cox regression analysis revealed that TNFR2, Hangzhou criteria, age, and hepatitis B surface antigen were independent risk factors for post-transplant lung metastasis, and a novel nomogram was established accordingly. The nomogram achieved excellent prognostic efficiency (area under time-dependent receiver operating characteristic =0.755, concordance-index =0.779) and was superior to conventional models, such as the Milan criteria., Conclusions: TNFR2 is a potent prognostic biomarker for predicting post-transplant lung metastasis in patients with HCC. A nomogram incorporating TNFR2 deserves to be a helpful prognostic tool in liver transplantation for HCC., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (Copyright ©2023 Chinese Journal of Cancer Research. All rights reserved.)

Background: We aimed to investigate whether D-dimer and fibrinogen levels could predict prognosis of patients with hepatocellular carcinoma (HCC) following liver transplantation., Methods: From January 2015 to January 2020, we conducted a study on patients with hepatitis B-related liver cancer. Two hundred seventy (270) liver transplant recipients were recruited. Considering D-dimer and plasma fibrinogen levels, a model was established to predict liver cancer recurrence following liver transplantation. Subsequent verification was performed on a validation cohort of 295 recipients from two other hospitals., Results: Elevated D-dimer and plasma fibrinogen levels demonstrated independent correlation between overall survival and tumour-free survival among patients with HCC who underwent liver transplantation. Those who had preoperative fibrinogen ≥2.27 g/L had significantly reduced overall survival and tumour-free survival than those who had preoperative fibrinogen <2.27 g/L, in the discovery cohort. Recipients with increased risk had preoperative plasma D-dimer ≥2400 µg/L. The model was: Y= logit (P) =0.91* fibrinogen concentration +0.967* D-dimer +0.585* alpha-fetoprotein +1.623* Milan criteria +0.68* microvascular invasion -3.159. At a cut-off score of -1.524, the validation cohort had area under curve values of 0.764 and 0.828 respectively; analysis of this data optimised predictive performance for overall and tumour-free survival., Conclusions: For patients who have undergone liver transplantation for HCC, preoperative D-dimer and fibrinogen levels independently predicted key outcomes such as overall survival and tumour-free survival., Competing Interests: None., (AJTR Copyright © 2022.)