An interferon-free combination of sofosbuvir (Sovaldi) plus ribavirin taken for up to 24 weeks led to sustained virological response in 70% of liver transplant recipients with hepatitis C virus (HCV) recurrence, according to a poster presented at the 49th annual meeting of the European Association for the Study of the Liver (EASL), held recently in London.
Direct-acting antiviral agents (DAAs) have begun to revolutionise treatment for chronic hepatitis C. The first of the next-generation DAAs – Gilead Sciences' HCV polymerase inhibitor sofosbuvir and Janssen's HCV protease inhibitor simeprevir (Olysio) – were approved late last year, and several more are in the pipeline. But therapeutic options remain scarce for people with severe liver disease who have the most urgent need for treatment.
Didier Samuel of Université Paris-Sud and colleagues conducted a single-arm, open-label study of sofosbuvir plus ribavirin for liver transplant recipients who experienced HCV recurrence.
Hepatitis C virus almost always re-infects the new liver after a transplant. This can lead to rapid fibrosis progression with an increased risk of graft loss and life-threatening complications. Interferon – the former standard of care for hepatitis C – is often poorly tolerated and not very effective for people with advanced liver disease. Sofosbuvir is a promising option because it is well tolerated and does not interact with immunosuppressant drugs used to prevent organ rejection.
This analysis included 40 people with hepatitis C who underwent transplants at least six months (median 4.3 years) prior to enrolment in the study. A majority (78%) were men, most were white and the mean age was 59 years. More than half had hard-to-treat HCV genotype 1a, 28% had genotype 1b, 15% had genotype 3 and one person had genotype 4. One-third had the favourable IL28B CC gene variant. Most (88%) had previously been treated but not cured with interferon-based therapy. Forty per cent had liver cirrhosis (stage F4), but those with symptoms of liver decompensation were excluded.
All participants received 400mg sofosbuvir once daily plus ribavirin starting at a low dose of 400mg per day and escalating, if tolerated, toward the standard upper dose of 1200mg per day. Treatment lasted for up to 24 weeks (average duration 23 weeks) and participants were followed for 12 and 24 weeks post-treatment to determine sustained virological response (SVR12 and SVR24), considered to be a cure.
By treatment week 4, 100% of participants in the study had undetectable HCV viral load (<25 IU/ml). The end-of-treatment response rate was also 100%. A number of participants relapsed after completing therapy, however, resulting in a sustained virological response rate of 70% at both 12 and 24 weeks post-treatment. Ribavirin doses were similar in people who achieved SVR and those who relapsed.
Sofosbuvir plus ribavirin was generally safe and well tolerated. Six people experienced serious adverse events and two discontinued treatment due to adverse events. The most common side-effects were fatigue, diarrhoea, headache, joint pain and nausea. Anaemia was common, with 28% of participants reducing their ribavirin dose and 20% receiving erythropoietin or blood product transfusions. No deaths, graft loss, acute or chronic organ rejection or drug-drug interactions between sofosbuvir and immunosuppressants were reported.
"High SVR rates were achieved in this difficult-to-treat population," the researchers concluded. "Sofosbuvir plus ribavirin was a potent all-oral therapy for treatment of HCV infection following liver transplantation."
Samuel D et al. Sofosbuvir and ribavirin for the treatment of recurrent hepatitis C infection after liver transplantation: results of a prospective, multicenter study. 49th Annual Meeting of the European Association for the Study of the Liver (EASL), abstract P1232, London, 2014.