Sofosbuvir for Hepatitis C: Simpler, Shorter, Safer?

William F. Balistreri, MD


December 03, 2013

In This Article

New Opportunities Bring New Challenges

Recurrence of HCV infection is the most common cause of graft loss and mortality in HCV-infected liver transplant recipients. IFN-based post-transplantation antiviral regimens, including those using protease inhibitors, are poorly tolerated and achieve SVRs that are lower than those in nontransplant patients.

Administration of sofosbuvir plus ribavirin after liver transplantation in the setting of established HCV recurrence was well tolerated, and approximately 80% of patients achieved an early SVR at 4 weeks. There were no episodes of rejection or drug interaction, and there was no apparent effect of sofosbuvir on serum levels of immunosuppressive medications, offering the potential for an all-oral therapy for treatment of HCV infection after liver transplantation.[22] Sofosbuvir and ribavirin may, in fact, be used in the pretransplant phase to prevent recurrence of HCV infection after transplantation.[23]

In summary, 2 novel direct-acting antiviral agents -- sofosbuvir and simeprevir -- target various components of the HCV genome. Advantages of these drugs include a high barrier to viral resistance, a shorter duration of treatment, once-daily dosing, absence of food restrictions, few clinically significant drug interactions, and similar efficacy in all genotypes. This will offer clinicians new options as well as new challenges. A recent review addressed some of these anticipated issues, such as the off-label use of HCV medications and the roles of the FDA, consumer pressure, medical society guidelines, and third-party payers.[24]

The availability of these agents will provide unprecedented opportunities for off-label use of these therapies in many patients, including those with decompensated cirrhosis or chronic kidney disease, pediatric populations, and those with HIV coinfection. Because many of these populations represent relatively small numbers of patients with HCV, it may be difficult to accumulate the requisite data and possibly cost-prohibitive for manufacturers to apply for FDA approval.

The bottom line is that simpler, shorter, and safer strategies for treatment of patients infected with HCV are at hand.


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