The Institute for Safe Medication Practices (ISMP) reported on 524 cases of liver failure in the past 12 months associated with direct-acting antiviral agents for treating hepatitis C. The investigation included 24 cases of hepatitis B reactivation that were widely reported last October. But now, the ISMP has reviewed hundreds of other cases of liver failure associated with the drugs and more than 1,000 cases of severe liver injury. According to the report, 165 patients have died. All the new antivirals for hepatitis C were implicated, including sofosbuvir (Sovaldi), ledipasvir-sofosbuvir (Harvoni), and simeprevir (Olysio). Gilead Sciences suggests that approval of its drug sofosbuvir for treatment of patients with liver failure may account for some of the cases. However, the ISMP reported that the vast majority of these cases were reported by healthcare professionals to FDA’s MedWatch program for adverse drug events. Further, the ISMP suggested that “Our data show the need for further investigation into the negative consequences of these expensive and important new drugs” ( Most experts agree that the drugs must be used with caution by those well-versed in hepatitis C treatment, but given the remarkably high cure rates, the benefits generally outweigh the risks.