In the face of increasing morbidity and mortality, better therapies for Hepatitis C have emerged which if applied broadly have an opportunity to change the outcome.  Recently, several articles have highlighted the possibility of treating individuals without interferon.

• Lok et al. NEJM 2012; 366: 216-224
• Chayam et al. Hepatology 2012; 55: 742-48
• Zeuzem et al. Hepatology 2012; 55: 749-58.

In the Lok study, 21 null responders (patients who failed to achieve ≥2log10 decline in HCV RNA after ≥12 weeks of peginterferon and ribavirin) were divided into two groups. In Group A, 36% of patients were able to achieve SVR12 using a combination direct-acting antivirals (DAAs) with non-overlapping resistance profiles — without the use of interferon. Group A patients received BMS-790052 (an oral, first-in-class, NS5A replication complex inhibitor) and BMS-650032 (an oral NS3 protease inhibitor). In Group B which included peginterferon and ribavirin the SVR12 was 100%. There were no serious adverse events, or discontinuations.  The most common side effects were diarrhea, fatigue, headache, and nausea.

In the Chayam study, the combination of BMS-790052 (now called daclatasvir) and BMS-650032 (now called asunaprevir) examined this combination of DAAs in null HCV responders with genotype 1B (in Japan).  Ten patients received both drugs for 24 weeks. All nine who completed treatment had an SVR.  One patient stopped the medication due to elevated bilirubin and lymphopenia which occurred following an apparent infectious gastroenteritis.

In the Zeuzem study, tegobuvir (a nonnucleoside polymerase inhibitor) and GS 9256 (an NS3 serine protease inhibitor) with RBV (n=15), with PEG/RBV (n=15) and without ribavirin (n=16) were administered in three arms for 4 weeks, followed by dual therapy with PEG and RBV.  The primary end point was rapid virologic response (RVR), defined as HCV RNA <25 IU/mL.  Reductions (mean) for HCV RNA were -4.1 log10 IU/mL for dual therapy, -5.1 log10 IU/mL for triple therapy, and -5.7 log10 IU/mL for quadruple therapy.  RVR was noted in 7% of dual Rx, 38% of triple therapy, and 100% of quadruple therapy.

These studies indicate that even for difficult to treat HCV patients that new oral medications are on the horizon that will increase cure rates and may allow effective regimens that do not include interferon.  This is good news because until recently regimens with interferon were more likely to provoke adverse reactions that to guarantee a cure.

Links to relevant blog entries on HCV:

HCV now more deadly than HIV

The cost of progress in treating Hepatitis C

Looking for trouble