Tumor micronecrosis predicts poor prognosis of patients with hepatocellular carcinoma after liver transplantation

Abstract

Background Tumor micronecrosis is a histopathological feature predicting poor prognosis in patients with hepatocellular carcinoma (HCC) who underwent liver resection. However, the role of tumor micronecrosis in liver transplantation remains unclear. Methods We retrospectively reviewed patients with HCC who underwent liver transplantation between January 2015 and December 2021 at our center. We then classified them into micronecrosis(−) and micronecrosis(+) groups and compared their recurrence-free survival (RFS) and overall survival (OS). We identified independent prognostic factors using Cox regression analysis and calculated the area under the receiver operating characteristic curve (AUC) to evaluate the predictive value of RFS for patients with HCC after liver transplantation. Results A total of 370 cases with evaluable histological sections were included. Patients of the micronecrosis(+) group had a significantly shorter RFS than those of the micronecrosis(−) group (P = 0.037). Shorter RFS and OS were observed in micronecrosis(+) patients without bridging treatments before liver transplantation (P = 0.002 and P = 0.007), while no differences were detected in those with preoperative antitumor therapies that could cause iatrogenic tumor necrosis. Tumor micronecrosis improved the AUC of Milan criteria (0.77–0.79), the model for end-stage liver disease score (0.70–0.76), and serum alpha-fetoprotein (0.63–0.71) for the prediction of prognosis after liver transplantation. Conclusion Patients with HCC with tumor micronecrosis suffer from a worse prognosis than those without this feature. Tumor micronecrosis can help predict RFS after liver transplantation. Therefore, patients with HCC with tumor micronecrosis should be treated with adjuvant therapy and closely followed after liver transplantation. Clinical trials registration Not Applicable.

Imaging prognostication and tumor biology in hepatocellular carcinoma

“… 88 Extensive cellular hypoxia has been associated with increased metastatic potential and poorer sensitivity to radiotherapy and chemotherapy. 89 Wang et al 90 demonstrated that tumor micronecrosis (tumor necrosis that can only be observed histologically) can independently predict decreased recurrance free and overall survival after liver transplantation, indicating the need for close follow up after treatment. Moreover, the histologic subtype of necrosis (e.g., neutrophil-rich, scirrhous and lymphocyte-rich) has been shown to influence prognosis after TACE, with liquefactive necrosis associated with increased rate of recurrence and metastasis.…”

“…These regions of necrosis can be found in rapidly expanding tumors due to hypoxia, as described by Tohme et al 88 Extensive cellular hypoxia has been associated with increased metastatic potential and poorer sensitivity to radiotherapy and chemotherapy. 89 Wang et al 90 with liquefactive necrosis associated with increased rate of recurrence and metastasis. 91…”