Tumor micronecrosis is a marker of poor prognosis of hepatocellular carcinoma after liver resection.

[BACKGROUND] Tumor micronecrosis is a feature of hepatocellular carcinoma (HCC) and might mirror tumor characteristics and patient prognosis. However, the specific influence of tumor micronecrosis on the recurrence patterns of HCC remains unclear. This study aimed to investigate the effects of tumor micronecrosis on HCC recurrence patterns, particularly examining any changes after liver resection.

[METHODS] A cohort of 938 patients with primary HCC who underwent R0 liver resection between June 2014 and October 2019 were included in the study. A second R0 resection was performed in 340 patients with tumor recurrence between November 2014 and October 2021. Tumor micronecrosis was evaluated for primary (938 cases) and recurrent (340 cases) tumors. The recurrence pattern and prognosis were analyzed, and independent prognostic factors were identified using Cox regression analysis. Nomograms were then constructed to predict tumor recurrence and prognosis after liver resection.

[RESULTS] HCC recurrence was observed in 400 (42.6%) patients during the follow-up period. Tumor micronecrosis independently affected recurrence-free survival (P = 0.002). Among micronecrosis (+) patients, a higher extrahepatic recurrence, multiple tumors, elevated albumin-bilirubin grade, advanced Barcelona Clinic Liver Cancer stage, and increased alpha-fetoprotein level were observed. Additionally, more micronecrosis (-) patients underwent positive treatments after recurrence (P = 0.017), leading to a superior post-recurrence prognosis in this group (P < 0.001). Nearly half of the recurrent HCCs displayed changes in tumor micronecrosis scores. The presence of micronecrosis in primary lesions was significantly associated with poor patient survival after recurrence (P = 0.006), whereas no significant association was observed in patients with recurrent lesions after second R0 resection (P = 0.138). Furthermore, early recurrence, multinodular recurrence, intrahepatic and extrahepatic recurrent tumors, and the treatment modality were identified as independent prognostic factors. The developed nomogram for patient survival achieved a concordance index of 0.753.

[CONCLUSIONS] Patients with HCC displaying tumor micronecrosis experienced increased recurrent risks and more aggressive recurrent patterns, and encountered poorer prognosis compared to those without micronecrosis. Notably, micronecrosis status often varied between primary and recurrent HCCs. However, micronecrosis predicted survival only when evaluated in the primary tumor, not in the recurrent tumors.