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
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.
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.
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.
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.
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."