Impact of underlying liver etiology on post-hepatectomy survival outcomes in hepatocellular carcinoma patients.

BACKGROUND

The underlying etiology of liver disease, such as metabolic dysfunction-associated steatotic liver diseases (MASLDs) or alcohol-related liver injury, significantly affects liver function and regenerative capacity. In hepatocellular carcinoma (HCC) patients undergoing hepatectomy, these background factors may influence postoperative outcomes and long-term survival. This study aimed to evaluate the impact of different etiologies of liver disease on survival outcomes following curative hepatectomy in patients with HCC.

METHODS

We retrospectively analyzed patients with HCC who underwent curative hepatectomy at two academic institutions. Background liver disease was classified according to etiology, including viral liver disease (VLD), alcohol-related liver disease (ALD), MASLD, and others. Survival outcomes were evaluated and compared across etiological groups at two institutions from 1994 to 2023.

RESULTS

Patients with VLD, ALD, and MASLD exhibited significantly elevated rates of advanced liver fibrosis (P<0.001), while vascular involvement was less frequent in MASLD cases. No significant differences in tumor stage, tumor markers, or postoperative complications were found among the etiologies. However, tumor recurrence was significantly more common in the VLD and ALD groups (P<0.001), and HCC-related deaths were most frequent in the VLD and other/unknown groups. MASLD patients presented the most favorable outcomes, with a 5-year recurrence-free survival (RFS) of 54% and a 10-year overall survival (OS) of 100%, significantly better than VLD (RFS 31%, OS 49%; P<0.01). Multivariate analysis revealed that VLD, vascular invasion, R1 margin, and poor liver function were independent predictors of recurrence and poor OS. Conversely, MASLD was not a significant risk factor for recurrence and was independently associated with better survival (P<0.05).

CONCLUSIONS

MASLD-related HCC represents a distinct clinical entity with relatively indolent tumor behavior and better-preserved liver function. Recognizing the prognostic implications of MASLD-related HCC is essential for optimizing surgical indications and developing etiology-specific treatment strategies.