An unfortunate failure: multifocal hepatocellular carcinoma in a non-cirrhotic patient with chronic hepatitis C treated with ledipasvir/sofosbuvir

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is the third highest cause of cancer mortality worldwide. Risk factors include chronic liver disease and cirrhosis of various causes including chronic hepatitis B and C. In cases of chronic hepatitis C virus (HCV), HCC usually does not manifest unless the liver has become cirrhotic. Fortunately, novel treatments for hepatitis C including ledipasvir/sofosbuvir can cure patients from their disease and as a result, may never develop cirrhosis and therefore, be at much lower risk of developing HCC. We present a patient with chronic HCV genotype 1a who was successfully treated with ledipasvir/sofosbuvir with documented sustained viral response, but 6 months later was found to have multifocal HCC with virus reactivation with no evidence of cirrhosis on imaging or biochemical testing. While novel antiviral agents for HCV lead to >90% cure rate, cure is defined as sustained viral response of only 12 weeks. This brings to light a new patient population who may require further follow-up than 3 months to ensure viral clearance. Furthermore, this patient developed HCC despite initial viral clearance and no evidence of cirrhosis, indicating possible oncogenic potential of HCV that is independent of cirrhosis that necessitates further investigation.