Recurrence and tumor-related death after resection of hepatocellular carcinoma in patients with metabolic syndrome

Background and aims Metabolic syndrome (MS) is a growing epidemic and a risk factor for the development of hepatocellular carcinoma (HCC). This study aims to investigate the long-term outcomes of liver resection (LR) for HCC in patients with MS. Rates, timing, patterns, and treatment of recurrences were investigated, and cancer-specific survivals were assessed. Methods Between 2001 and 2021, data from 24 centers were collected. Overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival were analyzed as well as recurrence patterns and treatment. The analysis was conducted using a competing-risk framework. The trajectory of the risk of recurrence over time was applied to a competing risk analysis. For post-recurrence survival, death due to tumor progression was the primary endpoint whereas deaths with recurrence due to other causes were considered as competing events. Results 813 patients were included. Median OS was 81.4 months (28.1-157.0), and recurrence occurred in 48.3% of patients with a median RFS of 39.8 months (15.7-174.7). Cause-specific hazard of recurrence showed a first peak 6 months (0.027), and a second peak 24 months (0.021) after surgery. The later the recurrence, the higher the chance of receiving curative intent approaches (p=0.001). Size >5cm, multiple tumors, microvascular invasion, and cirrhosis were independent predictors of recurrence showing a cause-specific hazard over time. RFS was associated with death for recurrence (HR 0.985, 95%CI: 0.977, 0.995; p=0.002). Conclusions Patients with MS undergoing LR for HCC have good long-term survival. Recurrence occurs in 48% of patients with a double peak incidence and time-specific hazards depending on tumor-related factors and underlying disease. The timing of recurrence significantly impacts survival. Surveillance after resection should be adjusted over time depending on risk factors.