This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker’s bureau, research, or other financial relationships with companies having ties to this field of study. For questions and comments, please e-mail:

Advances in the treatment of hepatitis C virus (HCV) are occurring at breakneck speed, with new drugs and new drug combinations showing astounding cure rates, but coupled with astounding price tags. No sooner was sofosbuvir approved and marketed at a cost of $84,000 per treatment course, that new drug combinations started emerging, some containing sofosbuvir. The importance of these drugs is demonstrated by a few statistics — as many as 170 million people are infected with HCV worldwide, including 3.2 million Americans. It is the most common cause of liver-related death and liver transplant in the United States, and HCV recently passed HIV as a cause of death in this country. But the pace of research into treatment is impressive. In the last 2 months, six studies were published in the New England Journal of Medicine evaluating new drug regimens. Three of them looked at sofosbuvir/ledipasvir alone or in combination with ribavirin for treatment of genotype 1 hepatitis C. Ledipasvir is an unapproved NS5A inhibitor. The combination offers the advantage of an all oral, short-course, interferon-free regimen. Both in previously treated and untreated patients, sustained virologic responses were at least 94% with no additional benefit from ribavirin. There was a very low discontinuation rate with all regimens (N Engl J Med 2014;370:1483-1493, 1879-1888, 1889-1898). Sofosbuvir plus ribavirin was also shown to be highly effective for treating HCV genotypes 2 and 3 (N Engl J Med published online May 4, 2014, doi: 10.1056/NEJMoa1316145). Finally, two studies looked at a new highly active, interferon-free regimen of a new protease inhibitor with ritonavir (ABT-450/r), the NS5A inhibitor ombitasvir, and the nonnucleoside polymerase inhibitor dasabuvir with ribavirin in patients with HCV genotype 1. Sustained virologic response rates were 95% or higher in both untreated and previously treated individuals after 12 weeks. This regimen was also well tolerated with a low discontinuation rate (N Engl J Med 2014;370:1594-1603, 1604-1614). This is very promising news, except for the cost of treatment, which is also expected to escalate. As one editorialist puts it “The predicted costs of the new oral antiviral agents are as breathtaking as their effectiveness” (N Engl J Med2014;370:1552-1553.)