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Background Liver transplantation (LT) is the treatment of choice for patients with unresectable early hepatocellular carcinoma (HCC). Post-LT HCC recurrence rates range from 8 to 20% and still impact on overall survival (OS). The aim of our study was to evaluate the impact of HCC recurrence on post-LT survival and analyze prognostic factors among those patients with recurrence. Patients and methods We carried out a national, multicenter, retrospective cohort study in Brazil. Medical records of 1119 LT recipients with HCC were collected. Data from patients with post-LT HCC recurrence were analyzed and correlated with post-relapse survival. Results OS of the 1119 patients included in the study was 63% over 5 years. Post-LT HCC recurrence occurred in 86 (8%) patients. The mean time to recurrence was 12 months. Sites of recurrence were extrahepatic in 55%, hepatic in 27%, and both hepatic and extrahepatic in 18%. Recurrence treatment was performed in 50 (64%) cases, mostly with sorafenib. Post-relapse survival rates were 34% at 1 year and 13% at 5 years. Univariable analysis identified α-fetoprotein more than 1000 ng/ml at relapse, recurrence treatment, extrahepatic location, and time to recurrence more than 2 years as prognostic factors. In multivariable analysis, recurrence treatment, extrahepatic location, and time to recurrence more than 2 years were independent predictors of better survival. Conclusion In a large Brazilian cohort of LT recipients with HCC, post-LT HCC recurrence occurred in 8% and impacted significantly on the OS. Patients with early recurrence presented a worse prognosis. However, treatment of recurrence improved outcomes, highlighting the importance of early diagnosis.

S-HCC and FL-HCC are subtypes of HCC with extensive fibrosis, and the nature of the fibrous stroma differs between them. While the stroma of FL-HCC is composed of dense lamellated collagenous bands with sparse cellular components, S-HCC demonstrates more abundant CAF and tumour-infiltrating macrophages and stemness-related marker expression, suggesting the presence of a complex tumour microenvironment that may influence the aggressive behaviour of S-HCCs.

Identification of HCC smaller than 20 mm is associated with longer survival. Presence of vascular invasion, even in small tumors, maybe associated with poor prognosis. Treatment of small tumors of up to 20 mm diameter is related to increased survival.

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