Treatment for chronic hepatitis C depends on the hepatitis C virus (HCV) 
genotype and the patient's clinical characteristics. A fixed-dose combination of 
ledipasvir + sofosbuvir has been authorised in the European Union for adults 
with HCV genotype 1 (HCV-1), HCV-3 or HCV-4 infection. Ledipasvir targets the 
HCV protein NS5A, while sofosbuvir inhibits the HCV RNA polymerase NS5B. The 
ledipasvir+ sofosbuvircombination has not been compared directly with other 
antiviral drugs. No information is available on its ability to prevent hepatic 
complications, even in patients with cirrhosis. In four trials including over 
1800 treatment-naive patients infected with HCV-1, a 12-week course of 
ledipasvir + sofosbuviryielded a sustained virological response in nearly every 
case. This is better than that reported with peginterferon alfa-based protocols. 
In four trials including more than 900 HCV-1-infected patients in whom 
treatments including peginterferon alfa had failed, a 24-week course of 
ledipasvir+ sofosbuvir yielded a sustained virological response in nearly every 
case, which is far better than reported with peginterferon alfa + ribavirin + 
protease inhibitor combinations, based on indirect comparison. In these trials, 
a 24-week course of the ledipasvir + sofosbuvir combination was effective in 
almost all patients with compensated cirrhosis. The same treatment also showed 
major efficacy in a non-comparative trial in 337 HCV-1-infected patients with 
decompensated cirrhosis or who had undergone liver transplantation. In mid-2015, 
very few data are available on the ledipasvir + sofosbuvir combination in 
HCV-1-infected patients in whom sofosbuvir combination therapy has failed, or in 
patients with HCV-3 or HCV-4 infection. Comparative data on the adverse effects 
of the ledipasvir + sofosbuvir combination are mainly based on a double-blind, 
placebo-controlled trial in 155 patients. Overall, serious adverse effects were 
infrequent in this and other trials. The main adverse effects appear to be 
headache, fatigue, sleep disorders, irritability and lipase elevations. 
Hypertension, muscle disorders and dyspnoea are other plausible adverse effects. 
Bradycardia and cardiac conduction disorders have been reported with concomitant 
use of sofosbuvir and amiodarone, an antiarrhythmic drug. In practice, in 
mid-2015, when drug therapy is warranted for chronic hepatitis C due to HCV 
genotype 1, the ledipasvir + sofosbuvir combination is a first-choice treatment 
because of its virological efficacy, despite its poorly documented adverse 
effects. These important outstanding questions call for rigorous 
pharmacovigilance on the part of all healthcare professionals. It is too early 
to recommend the ledipasvir + sofosbuvir combination for patients infected with 
other HCV genotypes. The exorbitant price imposed by Gilead endangers public 
healthcare systems and undermines access to high-quality care.