The anti‐viral effect of sorafenib in hepatitis C‐related hepatocellular carcinoma

Abstract

Background and Aim Sorafenib is currently the only approved systemic therapy shown to have efficacy in the treatment of advanced hepatocellular carcinoma (HCC). Recent studies suggest that hepatitis C (HCV)-related HCC patients derive more clinical benefit from sorafenib than other subgroups, but the mechanism for this effect is unknown. In-vitro data suggest that sorafenib may exert antiviral properties and thus our aim in this study, was to evaluate potential antiviral activity of sorafenib in patients with HCV-related HCC. Methods We prospectively enrolled patients with HCV-related HCC treated with sorafenib for up to six months. Baseline clinical, viral, and oncologic data were collected. Patients’ HCV viral loads were obtained at various timepoints, and compared to their baseline viral levels. No patients received any known antiviral therapy during this time. Results Thirty-three patients were identified with baseline and subsequent HCV levels available for analysis. Six patients completed six months of full dose sorafenib, and comparisons of their HCV viral loads showed no significant change at week 24 (difference of means = 0.3500, C.I. = −0.1799 to 0.8799, p = 0.150), or the interim time points. Similarly, the HCV viral loads of all patients who received sorafenib and the viral loads of those patients who had tumor response to sorafenib showed no significant changes at any time point. Conclusion Despite preclinical data and previous subgroup analyses suggesting that sorafenib has antiviral effect against HCV, this study suggests that sorafenib lacks significant anti-viral activity in HCV patients with HCC.

Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: Subanalyses of a phase III trial

“…In addition, in vitro results in the human HuH7.5 liver cancer cell line have suggested that sorafenib inhibits HCV replication [29]. Recent results have shown, however, that sorafenib had little or no effect on HCV viral load in 18 patients with HCV-associated HCC [30]. Thus, the combined results of these trials suggest that sorafenib is effective for the treatment of advanced HCC irrespective of viral etiology.…”

Potential molecular, cellular and microenvironmental mechanism of sorafenib resistance in hepatocellular carcinoma

“…Two recent studies reported that sorafenib exhibited a potent anti-replicative efficacy on HCV [126,127]. An opposite result was shown in another study, which reported that sorafenib impaired the antiviral effect of interferon alpha on hepatitis C virus replication [128].…”

Letter: the antiviral activity of sorafenib in patients with hepatitis C‐related hepatocellular carcinoma

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SIRS, We read with great interest the paper by Cabrera et al 1 Their study suggests that sorafenib lacks significant antiviral activity in hepatitis C virus (HCV) patients with hepatocellular carcinoma (HCC), which is consistent with the results in subgroup analysis of the SHARP trial. 2 The latter had indicated that patients with HCVrelated HCC had improved survival and time to progression when treated with sorafenib compared with patients with non-HCV-related HCC.

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