Treatment of Hepatitis C: At Last the Holy Grail
Kurt J. Isselbacher Distinguished Mallinckrodt Professor of Medicine, Harvard Medical School; Physician and Director, Massachusetts General Hospital Cancer Center, Boston

Chronic hepatitis C is a major cause of liver cirrhosis and hepatocellular carcinoma. In fact it is estimated that about 3% of the world’s population is chronically infected with the hepatitis C virus (HCV). Until recently the treatment of HCV has left a lot to be desired. One of the key limitations has been that the therapeutic regimen has included interferon, which in many patients is associated with disturbing and debilitating side effects. In addition, the current treatment leads to a sustained viral response in only 45–70% of patients as well as a high incidence of disease recurrence. Furthermore, the treatment requires parenteral rather than oral therapy.

Now a number of clinical trials have finally shown that an effective treatment can be achieved using an oral tablet containing two direct-acting antiviral agents (Afdhal and colleagues, 2014; Pawlotsky, 2014). These agents target key proteases and polymerases that are essential for HCV replication. Most of these trials included the use of ledipasvir and sofosbuvir (or their variants), which have potent activity against HCV. These drugs were given daily as oral tablets for 8, 12, or 24 weeks with or without ribavirin. The results were consistent and striking—namely, the various regimens yielded rates of sustained virologic response of 93–99%. Even without ribavirin, the response rates after 12 weeks ranged from 94% to 99%. It is also noteworthy that the single-tablet regimen was easy to administer and had few side effects[]. Among the patients who received the two antiviral agents alone for 12 weeks, very few stopped therapy because of adverse events (Chung and Baumert, 2014).

We will hear much more about these and other direct-acting antiviral agents for the treatment of HCV, but one thing is certain—namely, we have reached a major milestone and now have available a spectrum of direct anti-HCV drugs that augur well for curing this terrible disease.

Unfortunately, there is one caveat that qualifies all of the good news. The cost of the treatment is enormous. At present, a 12-week treatment of sofosbuvir alone costs $84,000, or approximately $1000 per tablet (Hoofnagle and Sherker, 2014). The addition of ledipasvir obviously will add to this cost.