Triple therapy for hepatitis C is effective after liver transplantation, but side-effects are common

This article is more than 8 years old. Click here for more recent articles on this topic

Adding the approved HCV protease inhibitor telaprevir (Incivo or Incivek) to pegylated interferon and ribavirin can increase sustained viral response rates even for difficult-to-treat liver transplant recipients, but adverse events are common, researchers reported at the 48th International Liver Congress (EASL 2013) last month in Amsterdam.

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 six US centres.

Glossary

pegylated interferon

Pegylated interferon, also known as peginterferon, is a chemically modified form of the standard interferon, sometimes used to treat hepatitis B and C. The difference between interferon and peginterferon is the PEG, which stands for a molecule called polyethylene glycol. The PEG does nothing to fight the virus. But by attaching it to the interferon (which does fight the virus), the interferon will stay in the blood much longer. 

tolerability

Term used to indicate how well a particular drug is tolerated when taken by people at the usual dosage. Good tolerability means that drug side-effects do not cause people to stop using the drug.

sustained virological response (SVR)

The continued, long-term suppression of a virus as a result of treatment. In hepatitis C, refers to undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 12 or 24 weeks after ending treatment and is considered to be a cure (SVR12 or SVR24).

creatinine

Breakdown product of creatine phosphate in muscle, usually produced at a fairly constant rate by the body (depending on muscle mass). As a blood test, it is an important indicator of the health of the kidneys because it is an easily measured by-product of muscle metabolism that is excreted unchanged by the kidneys.

antiviral

A drug that acts against a virus or viruses.

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 favourable 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. (This occurred as a consequence of adding telaprevir to an existing course of therapy.) 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 post-transplant 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 and 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 indicative of impaired kidney function. One in five experienced serious adverse events that required hospitalisation, 4% experienced liver graft rejection and 6% died during follow-up (4% due to liver-related causes).

"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."

References

Verna E et al. A multicenter study of protease inhibitor-triple therapy in HCV-infected liver transplant recipients: report from the CRUSH-C group. 48th International Liver Congress, Amsterdam, abstract 23, 2013.