Direct Acting Antivirals Before Surgical Resection of <scp>HCV</scp> Related <scp>HCC</scp> : 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.

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Journal
Liver International
Published
2026-06-09
DOI
https://doi.org/10.1111/liv.70738
Primary Topic
Hepatocellular Carcinoma Treatment and Prognosis
Type
article
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article

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

Stefano Di Sandro, Davide Ghinolfi, Daniele Nicolini, Maria Rendina et al.
Liver International
Hepatocellular Carcinoma Treatment and Prognosis
article

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

Stefano Di Sandro, Davide Ghinolfi, Daniele Nicolini, Maria Rendina, Mattia Garancini, Raffaella Tortora, Francesca Romana Ponziani, D. Pagano, Carlo Sposito, Giovanni Battista Levi Sandri, Umberto Baccarani, Fabio Melandro, Riccardo Pravisani, Francesco D’Amico, Giuseppina Brancaccio, Edoardo Giannini, A Vitale, U Cillo, F P Russo, M Cescon, Filomena Morisco, Tommaso Manzia, Felice Giuliante, Valerio Giannelli, Salvatore Gruttadauria, Fabrizio Romano, Quirino Lai, Leonardo Centonze, Giovanni Di Costanzo, Massimo A. Iavarone, Luca Viganò, Giovanni Battista Gaeta, Giuseppe Cabibbo
article en

Abstract

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.

Liver InternationalVol. 46(7)
University of Rome Tor Vergata (IT), University of Modena and Reggio Emilia (IT), Marche Polytechnic University (IT), University of Udine (IT), Humanitas University (IT), University of Padua (IT), University of Milan (IT), Policlinico Umberto I (IT), Agostino Gemelli University Polyclinic (IT), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), University of Catania (IT), Ospedale Maggiore (IT), Ospedale Antonio Cardarelli (IT), Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT), Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari (IT), Department of Health (ES), Federico II University Hospital (IT), Azienda USL di Bologna (IT), Humanitas Gavazzeni (IT), University of Campania "Luigi Vanvitelli" (IT), Azienda Ospedaliera Universitaria Università degli Studi della Campania Luigi Vanvitelli (IT), Ospedale Policlinico San Martino (IT), Carlo Forlanini Hospital (IT), Fondazione IRCCS Istituto Nazionale dei Tumori (IT), Azienda Ospedaliera Universitaria Pisana (IT), Link Campus University (IT), Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (IT), University of Bari Aldo Moro (IT), University of Milano-Bicocca (IT), University of Naples Federico II (IT), University of Bologna (IT)
Gilead Sciences
Good health and well-being
Openalex Percentile: Top 7%
Hepatocellular Carcinoma Treatment and Prognosis
DOISourceOpenAlex
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