Direct Acting Antivirals Before Surgical Resection of HCV Related HCC: Impact on Tumour Pathology and Outcomes

Background and aims: The impact of direct-acting antivirals (DAA) on the pathological characteristics and postoperative outcome of HCV-related hepatocellular carcinoma (HCC) in patients undergoing liver resection (LR) remains uncertain. We assessed aggressive tumour pathology (composite outcome comprising vascular invasion, poor grading or satellitosis), severe postoperative complications (Clavien-Dindo grade > 2), recurrence-free survival (RFS), and overall survival (OS) in patients with HCC treated with or without DAA before LR. Methods: Among 651 consecutive patients with HCV-related HCC who underwent LR in 17 Italian centres (2014-2016), we included 447 patients with concordant HCV-RNA status: 107 DAA-treated patients who were HCV-RNA-negative at resection (DAA-pre) and 340 HCV-RNA-positive patients without pre-resection DAA (No-DAA). DAA treatment was modelled as a time-varying covariate in Cox regression to avoid immortal time bias. Results: The DAA-pre group was younger (median age 66 vs. 70 years) and had smaller tumours (25 vs. 35 mm). Aggressive tumour pathology did not differ between groups (58.9% vs. 64.4%, p = 0.358). In multivariable analysis, DAA was not associated with aggressive pathology (OR 1.01, 95% CI 0.63-1.63, p = 0.961). Severe complications tended to be less common in DAA-pre patients (3.9% vs. 11.0%, p = 0.073) while hospital stay was shorter (6 vs. 7 days, p = 0.018). Time-varying multivariable Cox regression showed no significant association between DAA treatment and RFS (HR 0.87, 95% CI 0.66-1.16, p = 0.351), but a strong association with improved OS (HR 0.49, 95% CI 0.35-0.68, p < 0.001). Conclusions: Pre-resection DAA treatment did not affect tumour aggressiveness and tended to be associated with fewer severe early complications. Time-varying analyses suggested an additional survival benefit of DAA treatment, although in a single-arm observational cohort the relative contribution of pre- and post-resection DAA cannot be disentangled with certainty. These findings support viral eradication as early as possible, including before surgical resection of HCV-related HCC.