Prognostic Factors after Hepatectomy for Hepatocellular Carcinoma—The Importance of Pathological Immunophenotyping, the Steatohepatitic Subtype and the Impact of the Hepatic Pedicle Clamping

Abstract

Introduction: Hepatectomy (HP) is, along with liver transplantation, the only potentially curative treatment for Hepatocellular Carcinoma (HCC). The high prevalence of Metabolic Syndrome (MS) may be causing a shift in the HCC spectrum. Hepatic Pedicle Clamping (HPC), used to reduce perioperative bleeding during HP, has been theorized to increase the risk of recurrence. Cytokeratin 19 (CK19) and glypican-3 (GLP-3) have been identified as markers of worse prognosis in HCC. Materials and Methods: A clinical and pathological review of 59 patients undergoing HP for HCC between 2005 and 2013 was performed. Chronic liver disease was observed in 53 patients (89.8%), with cirrhosis in 54.2% [most frequent etiologies: ethylism (47.5%), HCV (25.4%) and HBV (11.9%)]. MS was in 36% of patients. In addition, 95% of patients had Child–Pugh class A and 5% class B, and there was a median MELD of 8 (6–18). A single nodule was observed in 46 patients (78%) with an average size of 5.4 cm. Microscopic vascular invasion (MiVI) was in 49% of patients and macroscopic (MaVI) in 17. HPC was in 43 patients (74.1%). Statistical analysis was performed with SPSS™ 21.0. Survival tests (Kaplan–Meier, log-rank and Cox regression). Statistical significance was with p < 0.05. Results: Major morbidity in 22% of patients. Mortality in 5.1%. Median overall survival (OS) of 71 months and median disease-free survival (DFS) of 37. In a multivariate analysis: MaVI (p = 0.001), MiVI (p = 0.005) and HCV infection (p = 0.002) were associated with worse OS; MS was associated with better OS (p = 0.001); MaVI (p = 0.000), MiVI (p = 0.035) and HPC (p = 0.012) were associated with worse DFS. CK19+/GLP-3− (p = 0.007) and CK19−/GLP-3+ (p = 0.029) patients were associated with worse DFS and CK19−/GLP-3− (p = 0.031) with better DFS. Discussion/Conclusions: HPC was an independent factor of worse DFS. The ischemia-reperfusion injury (IRI) produced by HPC could promote a more angiogenic and angioinvasive phenotype of tumor cells, resulting in higher recurrence. HCV etiology was associated with worse OS. MS was associated with better OS, highlighting the importance of a hepatectomy in these cases. The combined detection of CK19 and GLP-3 was an independent prognostic factor in HCC patients allowing for the identification of more aggressive tumors.