The Clinical Characteristics, Patterns of Recurrence, and Long-Term Survival Outcomes of Dual-Phenotype Hepatocellular Carcinoma After Curative Liver Resection.

Background & aims: Dual-phenotype hepatocellular carcinoma (DPHCC) is discernible from classical HCC (CHCC) in its morphology and is characterized by the co-expression of both CHCC and cholangiocyte markers. This study aimed to clarify the difference between DPHCC and CHCC after surgery.

Methods: Patients with HCC after surgery were collected. The clinical characteristics, patterns of recurrence, and survival outcomes of patients with DPHCC and CHCC were compared. Multivariate analyses were used to determine the independent risk factors that influence the prognosis of patients.

Results: Patients with DPHCC (n = 141) account for 26% of the total patients (n = 541). Compared to patients with CHCC, patients with DPHCC are significantly associated with incomplete capsules, microvascular invasion, and poor differentiation (all P < 0.05). Compared to patients with CHCC, the 5-year overall survival (OS) (56% vs 43%) and recurrence-free survival (RFS) (35% vs 28%) are lower in patients with DPHCC. Meanwhile, among patients with tumor recurrence after surgery, patients with DPHCC have a higher proportion of advanced-stage tumors, and extrahepatic metastasis (all P < 0.05). Moreover, multivariate analysis showed that DPHCC is an independent risk factor for both OS (HR 1.399, 95% CI 1.061-1.845, P = 0.017) and RFS (HR 1.313, 95% CI 1.033-1.669, P = 0.026).

Conclusion: DPHCC, an aggressive HCC subtype with poor differentiation and high invasiveness, shows inferior RFS and OS post-liver resection compared to CHCC. Clinicians' recognition and addressing of its unique challenges can improve DPHCC patients' prognosis and QoL.