Outcomes and safety of DAA treatment in HCV cirrhotic patients treated with Atezolizumab- Bevacizumab for hepatocellular carcinoma

Abstract

Background and Aims

Hepatitis C virus (HCV) infection is a critical driver of hepatocellular carcinoma (HCC) development and progression. Concurrent HCV treatment during systemic HCC therapy has not shown consistent benefits on survival and disease progression. This study aimed to evaluate safety and efficacy of Direct-Acting Antiviral (DAA) therapy in HCV-related HCC patients undergoing Atezolizumab-Bevacizumab (A/B), analysing its effects on overall survival (OS), time to progression (TTP), progression-free survival (PFS), liver decompensation rates.

Method

A total of 135 patients with HCV-related cirrhosis undergoing A/B treatment for HCC were enrolled from 2021 to 2024 and divided into groups based on HCV treatment status: an “active eradication” group (18 patients) who achieved sustained virological response (SVR) after DAA therapy concurrent with A/B treatment, a “prior eradication” group (95 patients) that reached SVR with DAAs or IFN-based regimens at least six months before starting A/B, and a “no eradication” group (22 patients) who did not obtain SVR at all.

Results

19 patients received SOF/VEL for 12 weeks achieving a 94.7% SVR rate, mostly due to elevated ALT and AST levels (94.4%). No adverse events (AEs) related to DAA therapy occurred during the treatment course.

The active eradication group demonstrated a significantly improved median OS that was not reached compared to the no eradication group (NA, 95% CI: 22.8–NA vs 20.0 months, 95% CI: 15.5–NA; p = 0.026). Regarding TTP, the active eradication group showed a median of 41.20 months (95% CI: 18.6– NA) compared to 21.3 months (95% CI: 5.13–NA) in no eradication group (p = 0.008). PFS results further supported the benefits of active eradication, with a median PFS of 41.17 months (95% CI: 22.80–NA) compared to 7.76 months (95% CI: 4.53–NA) in the no eradication group (p = 0.012). In contrast, the prior eradication group did not show significant survival benefits compared to the no eradication group for all outcomes. Liver decompensation rates did not differ significantly among groups (p > 0.05).

Conclusion

DAA therapy was safe and effective in patients with unresectable HCC receiving A/B treatment. DAA therapy during A/B significantly improved OS, TTP, and PFS in patients with HCV-related HCC, likely enhancing the A/B treatment effect through immunomodulatory mechanisms. This is particularly relevant in settings where maximizing disease control is critical, such as downstaging in patients undergoing liver transplantation.