2501 A Rare Case of Sofosbuvir/Velpatasvir/Voxilaprevir Failure in a Patient With Hepatitis C Virus Infection and Previously Undiagnosed Hepatocellular Carcinoma

Abstract

INTRODUCTION: The advent of direct acting antiviral (DAA) agents has revolutionized the treatment for chronic hepatitis C virus (HCV) infection with greater than 95% success rate. In 2017, a combination of sofosbuvir, velpatasvir, and voxilaprevir (sof-vel-vox) was approved after clinical trials demonstrated a 97-100% sustained virological response (SVR) rate in patients who had failed a previous NS5A inhibitor regimen. We present a rare case of treatment failure with sof-vel-vox in a non-cirrhotic patient with previously undiagnosed hepatocellular carcinoma (HCC). CASE DESCRIPTION/METHODS: The patient is a 68-year-old African-American male with a history of HCV-G1b infection who had previously failed treatment with a 12-week regimen of sofosbuvir/ledipasvir. He was subsequently retreated with 12 weeks of sof-vel-vox. He had an end of treatment response but had a viral relapse at 3 months post-treatment. He denied hepatitis exposure in the interim and repeat genotyping was G1b. He was compliant with his medications. He was referred to Hepatology for salvage treatment options. Prior labs and images did not show evidence of cirrhosis and he did not have a history of hepatic decompensations. Combined HIV Ab/Ag and Hepatitis B Core Ab were negative. A Fibrosure test revealed F3 fibrosis but unfortunately, he did not undergo HCC surveillance. At our initial evaluation a contrast MRI was ordered and revealed a 4.6 cm right lobe enhancing lesion with delayed washout consistent with HCC. Resection was not possible due to the location of the lesion, so he underwent locoregional therapy and is currently listed for liver transplantation with MELD exception. DISCUSSION: Treatment failure with sof-vel-vox is a rare event. Underlying HCC is known to be associated with lower SVR rates in patients treated with DAAs. Some have surmised a protection from eradication due to immunologic changes in cancer patients. We hypothesize that the presence of HCC was the most likely factor for this treatment failure. With sof-vel-vox as the last available option in the treatment paradigm, failure of this regimen in previous NS5A treated patients leads to a situation where there is not an available proven treatment regimen for salvage therapy. As such, we suggest that patients being considered for sof-vel-vox have “up to date” advanced imaging of the liver even in the absence of documented cirrhosis. If treatment failure does occur, one should consider the possibility of an underlying diagnosis of HCC.