As the International Liver Congress in London highlighted the stunning advance in treatments for hepatitis C, the New England Journal of Medicine has been weighing up "the costs of success".

The congress saw exciting data for a number of HCV interferon-free offerings, including Merck & Co's combination of the antivirals MK-5172 and MK-8742 which demonstrated a 12-week sustained virologic response (or viral cure) rate of 98% in genotype 1 patients. Also catching the eye is AbbVie's three-antivirals combo ABT-267, ABT-333 and ABT-450/ritonavir, developed with Enanta Pharmaceuticals.

However, an NEJM editorial focuses on "welcomed and exciting results" from three Phase III trials evaluating Gilead Sciences' Sovaldi (sofosbuvir) and the NS5A inhibitor ledipasvir. The authors note that the combined results of the three trials include 1,952 patients, of whom 97% had an SVR. Among the 3% who did not have a response, almost half were lost to follow-up or withdrew consent.

Gilead filed the combo with the US Food and Drug Administration in February and if approved, it would be the first oral treatment regimen for patients with genotype 1 HCV infection, eliminating the need for both interferon and ribavirin.

The NEJM editorial, written by Jay Hoofnagle and Averell Sherker, notes that ledipasvir and sofosbuvir are not the only promising antivirals "on the near horizon" and several other all-oral regimens have performed similarly in Phase II studies. Therefore, "there are likely to be several options for oral therapy of HCV within the next year", which will lead to "major changes in the management of this disease and probably affect both its morbidity and its mortality".

Since the first use of antivirals for HCV almost 30 years ago, treatment has been based on alpha interferon, which although being a potent treatment, has side effects issues and limited response rates of 50% or less. The authors note that the management of therapy requires physicians and healthcare staff with special expertise and despite the availability of interferon-based therapy for more than 20 years, "the mortality from HCV in the USA in the USA has continued to increase and now exceeds that from HIV infection".

Now the all-oral regimens promise to transform HCV but "not all barriers to treatment will be lifted", the authors state, noting, as have many observers, the  cost of a 12-week regimen of Sovaldi alone in the USA - $84,000. They state that the addition of ledipasvir will add to the costs, "and these estimates do not include expenses for diagnostic assays, monitoring, and physician visits."

Drs Hoofnagle and Sherker predict costs of the new oral antivirals are "as breathtaking as their effectiveness" as chronic HCV is estimated to affect 3.2 million Americans, half of whom may not be aware that they are infected. Even treating half of them "would add billions of dollars to an already overburdened medical care system [and] costs alone cast a pall over the stunning success in achieving the long-hoped-for goal of a safe and effective therapy".