Double Trouble: Chronic Hepatitis C and Hepatocellular Carcinoma

Abstract

Background: The advent of direct-acting antiviral (DAA) agents for Hepatitis C infection (HCV) has been shown to improve sustained virologic response rates (SVR) particularly given their favorable side effect profiles and thereby higher compliance rates as opposed to pegylated interferon and ribavirin. Novel research suggests the presence of a “hard to treat” group of patients that have active hepatocellular (HCC) and chronic HCV. This may be due to altered immunosurviellance and gene expression or simply radiologically undetectable lesions that became detectable after DAA initiation. We present a case series illustrating this group of “hard to treat” patients with chronic HCV and active /previously treated HCC. (Figure 1) _ Case 1: A 53 year old African American male with genotype 1a HCV cirrhosis and HCC treated with Ledipasvir/Sofosbuvir relapsed. For HCC, he was treated with radioactive embolization without discrete evidence of return of his tumor on Sorafenib (Alpha fetoprotein (AFP) = 5.6 ng/ml). He was retreated with Sofosbuvir/Velpatasvir with Ribavirin. His current viral load is 13345 copies. Case 2: A 72 year old Caucasian male (CM) with genotype 1A/2B HCV cirrhosis relapsed after Ledipasvir/Sofosbuvir therapy. Liver imaging demonstrated a 17 mm LI-RADS 4 lesion in segment 8 and 18 mm LI-RADS 3 lesion in segment 4A (AFP= 11.6 ng/ml) suspicious for development of HCC. He was retreated with Daclatsvir/Sofosbuvir with Ribavirin. His current HCV load is 11700000 copies. Case 3: A 60 year old CM with genotype 3a HCV cirrhosis and HCC treated with Yttrium-90 and Regorafenib was treated with Daclatsvir/Sofosbuvir with Ribavirin (AFP= 1.7 ng/ml). His viral load is 573011 copies. Case 4: A 59 year old CM with genotype 1a HCV cirrhosis and Hepatitis B core and HBe antibody positive (HBV DNA undetectable) complicated with multifocal HCC relapsed after Ledipasvir/Sofosbuvir therapy. He was retreated with velpatasvir/voxilaprevir with ribavirin. His HCC was treated with Y90 radio-embolization and Nivolumab (AFP = 5863 ng/ml). His viral load is 2201 copies. Conclusion Our case series demonstrates an inability to achieve SVR in patients with HCV and active/ previously treated HCC. While there is no current evidence to determine the exact etiology for the same, this appears to be an avenue that is yet to be studied in detail. This is an emerging group of “hard to treat” patients.2433 Figure 1. Case series illustrating a group of “hard to treat” patients with chronic HCV and active/previously treated HCC