Treatment of hepatitis C in difficult-to-treat patients.

Interferon-free regimes are now the treatment of choice for patients with chronic hepatitis C; previously patients who were 'difficult-to-treat' using interferon-containing treatments can now safely be treated with such therapies. More than 90% of patients infected with HCV genotype 1 or 4, compensated cirrhosis, or who have had liver transplantation, can be cured with the use of sofosbuvir combined with simeprevir, daclatasvir or ledipasvir, or by the combination of paritaprevir with ritonavir, ombitasvir and with or without dasabuvir. Addition of ribavirin seems to shorten treatment duration. However, the safety of these drugs is not fully explored in patients with decompensated cirrhosis (that is, those with Child-Pugh class C disease), and protease inhibitors should not be used in this group. The optimal use of interferon-free regimes in patients with renal failure or after kidney transplantation is currently being studied. However, new and improved drugs are needed to treat patients infected with HCV genotype 3. Unfortunately, the broad application of new HCV treatments is limited by their high costs. In this Review, I discuss the treatment of patients with hepatitis C with compensated and decompensated cirrhosis, before and after orthotopic liver transplantation and in patients with impaired kidney function.