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EASL 2013: Triple Therapy for Hepatitis C Is Effective after Liver Transplantation but Comes with Side Effects


Adding the approved HCV protease inhibitor telaprevir (Incivek or Incivo) to pegylated interferon and ribavirin can increase sustained response rates even for difficult-to-treat liver transplant recipients, but adverse events are common, researchers reported at the EASL International Liver Congress (EASL 2013) last month in Amsterdam.

[Editor's note: This report was revised to reflect updated results provided by the researchers.]

While many hepatitis C patients await interferon-free direct-acting antiviral regimens, others have advanced liver disease and need treatment now. This group includes liver transplant recipients, as HCV almost always recurs and infects the new liver in the absence of treatment.

Elizabeth Verna from Columbia University and fellow investigators with the CRUSH-C study evaluated triple therapy in a cohort of liver transplant recipients at 6 U.S. centers.

The analysis included 112 patients with HCV genotype 1 (55% with harder-to-treat subtype 1a). Nearly 80% were men, a majority were white, the median age was 58 years, and 26% had the favorable IL28B CC gene variant. Half had previously been treated with interferon-based therapy post-transplant, with 25% being relapsers, 27% being partial responders, and 48% being null responders. Most had moderate-to-severe fibrosis. Participants used various immunosuppressive regimens to prevent organ rejection including cyclosporine, mycophenolate mofetil, tacrolimus and steroids.

Participants were treated with pegylated interferon, ribavirin, and one of the first-generation HCV protease inhibitors, telaprevir or boceprevir (Victrelis). The median time since liver transplantation at the start of therapy was 3.7 years.

Most patients (88%) used telaprevir, almost all with a pegylated interferon/ribavirin lead-in. The median duration of treatment after starting the HCV protease inhibitor was about 36 weeks. Standard telaprevir triple therapy lasts 12 weeks, with pegylated interferon/ribavirin alone continued through week 24 or 48, depending on early response. People who received an extended lead-in of 90 days or longer were included in the safety but not the efficacy analysis.


  • Looking at early virological response among participants who had reached a given treatment duration, 66% of patients had undetectable HCV RNA at week 4 of treatment, rising to 84% at week 12.
  • Taken together, 64% had extended rapid virological response (eRVR) -- a good predictor of treatment success in pivotal trials of easier-to-treat patients.
  • Of the 43 patients who completed therapy and had at least 4 weeks of post-treatment follow-up, 65% achieved SVR4.
  • Among those with eRVR however, the SVR4 rate rose to 93%.
  • Extent of liver disease played a role, with 44% of patients with advanced disease (cirrhosis or fibrosing cholestatic hepatitis) achieving SVR4 compared with 71% of those without advanced disease.
  • Adverse events were common in this cohort.
  • 11% discontinued treatment for this reason (23% with advanced disease and 6% without).
  • A majority of patients used growth factors, reduced their doses of interferon or ribavirin, or required transfusions to manage blood cell deficiencies.
  • About one-third had creatinine increases indicating impaired kidney function.
  • 21% experienced serious adverse events necessitating hospitalization, 4% experienced liver graft rejection, and 6% died during follow-up (4% due to liver-related causes).

Post-treatment week 4 is too early to declare a cure; regulatory authorities now recognize treatment success at post-treatment week 12 (SVR12).

"High rates of eRVR are achievable with triple therapy exceeding previous rates with [pegylated interferon/ribavirin] alone despite a difficult to treat population," the researchers concluded. "SVR4 rates may be lower in patients with advanced disease."

"These results must be balanced with high rates of [adverse events], including hospitalization, kidney dysfunction and death," they continued. "Improving tolerability and identifying predictors of SVR are critical to optimizing the risks-benefits of post-liver transplant triple therapy."

5/10/13 [updated 5/15/13]


EC Verna, JR Burton, JG O'Leary, et al. A multicenter study of protease inhibitor-triple therapy in HCV-infected liver transplant recipients: report from the CRUSH-C group. 48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam. April 24-28, 2013. Abstract 23.