Advancements in Treatment for Hepatitis C, Part Two

This discussion is limited to non-cirrhotic patients. The goal of treatment is to eradicate HCV. In contrast, the goal of treatment for chronic hepatitis B is viral suppression. Patients who respond best to treatment include: non-cirrhotics, non-blacks, HCV RNA < 400K, and BMI <30. The eradication of HCV is predicted by achieving a sustained virologic response (SVR) as defined by the absence of HCV RNA 6 months after stopping treatment. An SVR is associated with a 99% chance of being HCV RNA negative during long-term follow up and improved clinical outcomes. Once therapy has been started, the likelihood that a patient will fail to achieve an SVR can be predicted by detectable HCV RNA at 12 weeks of therapy. After achieving SVR, there is a benefit of decreased mortality from liver-related mortality and a decreased rate of HCC. Interestingly, the rate of HCC decreases by 80% and not to zero. Therefore, some form of HCC surveillance should still be done in patients who achieve SVR.

The holy grail of chronic HCV treatment is to offer an effective all-oral regimen. That day has arrived with the FDA’s approval of the use of Sofosbuvir and Ribavirin (also an oral agent). Ultimately, we would like to eliminate the need for Ribavirin which too often leads to anemia. The expectations of all oral therapy are improved tolerability, less monitoring and complexity, accessibility to a greater number of patients and providers and high SVR rates. All oral regimens will likely entail 12 weeks of treatment with an expected SVR of 90% in treatment-naïve patients with genotypes 1 and 2. Patients with genotype 3 respond less well and require a longer duration of therapy.

Sofosbuvir is taken once daily, has an excellent safety profile, and is well-tolerated. Treatment regimens that include Sofosbuvir represent a significant improvement in efficacy. Ribavirin is administered twice daily.

The current therapies for genotypes 1-4 are listed below. Genotype 1 is the most common genotype in the U.S. Genotypes 5 and 6 are not adressed due to their low worldwide frequency.

Genotype 1

Current standard therapy is pegylated interferon (PEG) + ribavirin + boceprevir OR telaprevir for 24 weeks: SVR 70%

Sofosbuvir + PEG + ribavirin for 12 weeks. Treatment-naïve patients achieved an SVR of 89%

Sofosbuvir + ribavirin for 24 weeks for patients intolerant of PEG

Genotype 2

Current standard therapy is PEG + ribavirin for 24 weeks: SVR 75%

Sofosbuvir + ribavirin for 12 weeks. Treatmentnaïve patients achieved an SVR of 90%

Genotype 3

Current standard therapy is PEG + ribavirin for 24 weeks: SVR 70%

Sofosbuvir + ribavirin for 24 weeks. Treatmentnaïve patients achieved an SVR of 56%

Genotype 4

Current standard therapy is PEG + ribavirin for 48 weeks: SVR 50%

Sofosbuvir + PEG + ribavirin for 12 weeks.

Treatment-naïve patients achieved an SVR of 96%

Future Therapies

The future for the treatment of HCV is promising. Simeprevir and Faldaprevir are 2nd generation protease inhibitors. Simeprevir and Faldaprevir are given once daily and have an improved side effect profile with less anemia and rash than current protease inhibitors. In a phase 3 study, Simiprevir achieved an SVR of 80%. In a phase 3 study, Faldaprevir achieved an SVR of 80% in patients with genotype 1 treated for 24 weeks. Currently, multidrug all oral therapy regimens are showing an SVR of 88% in studies as short as 8 weeks.