Sofosbuvir is an oral nucleoside analogue and potent inhibitor of the hepatitis C virus (HCV) RNA polymerase that is used in combination with other antiviral agents to treat chronic hepatitis C. Elevations in serum enzyme levels during sofosbuvir therapy are uncommon, and it has not been implicated convincingly in cases of clinically apparent liver injury with jaundice. Nevertheless, and for unknown reasons, successful antiviral therapy of hepatitis C with sofosbuvir and other direct acting agents in patients with cirrhosis is occasionally complicated by hepatic decompensation; furthermore, treatment can cause reactivation of hepatitis B in susceptible patients coinfected with the hepatitis B virus (HBV).