HCC in the Era of Direct-Acting Antiviral Agents (DAAs): Surgical and Other Curative or Palliative Strategies in the Elderly

Simple Summary This study investigated HCC onset in a cohort of patients receiving DAA therapy for HCV infection. It highlights that HCC onset after HCV-clearance might show more aggressive behavior and might exclude the patient from curative treatments, such as surgery or radiofrequency ablation. Moreover, HCC may develop in livers with mild to moderate fibrosis, indicating that multiple factors (host immune response, host metabolism, etc.) may play an important role in determining the cancer onset or its recurrence after HCV eradication. It is crucial to classify long-term chronically infected patients as at high risk for HCC development and to implement strict follow-up for them after eradication. Hepatocellular carcinoma (HCC) accounts for 75-85% of primary liver malignancies, and elderlies have the highest incidence rates. Direct-acting antiviral agents (DAAs) have shown satisfying results in terms of HCV sustained viral response (SVR). However, data regarding HCC risk post-DAA-SVR is still conflicting. This study aims to consider HCC onset in moderate underlying liver disease. We conducted a retrospective study on 227 chronically infected patients (cHCV), treated with DAAs. Patients were divided into three groups: "de novo occurrent HCC", "recurrent HCC", and "without HCC". Fifty-six patients aged <65 years (yDAA) were studied separately. HCC patients aged >= 65 years (DAA-HCC) were compared to a historical group of 100 elderly HCC patients, treated with peginterferon (Peg-IFN) +/- ribavirin antiviral agents, non-SVR (hHCC). The HCC prevalence in DAA patients was 32.75%: "de novo occurrent'' 18.13% and "recurrent'' 14.62%, despite 42.85% of them having no fibrosis to mild or moderate fibrosis (F0-F1-F2). yDAA showed 5.36% "de novo occurrent" HCC. Curative procedure rates were compared between DAA-HCC and hHCC at the first and at recurrent presentation (22 (39.29%) vs. 72 (72%); 17 (30.36%) vs. 70 (70%), respectively (p < 0.001)). No significant difference was found in 3-year OS (p = 0.6). However, in cause-specific mortality analysis, HCC-related death was higher in the DAA-treated group, whereas cirrhosis-related death was more common in the historical group (p = 0.0288), considering together the two causes of death. A more accurate patient stratification according to multifactorial and new diagnostic investigations identifying HCC risk might allow an improvement in management and access to curative therapies.