EASL 2014: Sofosbuvir + Ribavirin Is Safe and Effective for HCV Recurrence after Liver Transplant

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 49thEASL International Liver Congress (EASL 2014) held recently in London.

The advent of effective direct-acting antiviral agents (DAAs) has begun to revolutionize 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 from Université Paris-Sud and colleagues conducted a single-arm, open-label study of sofosbuvir plus ribavirin for liver transplant recipients who experienced HCV recurrence.

HCV 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 donor organ rejection.

This analysis included 40 hepatitis C patients who underwent transplants at least 6 months (median 4.3 years) prior to enrollment. 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 1 person had genotype 4. One-third had the favorable IL28B CC gene variant. Most (88%) had previously been treated but not cured with interferon-based therapy. 40% had liver cirrhosis (stage F4), but those with current symptoms of liver decompensation were excluded; Child-Pugh scores were <7 and MELD scores were <17.

All participants all 400 mg sofosbuvir once-daily plus ribavirin starting at a low dose of 400 mg/day and escalating, if tolerated, toward the standard upper dose of 1200 mg/day. Treatment lasted for up to 24 weeks (average duration 23 weeks), and patients were followed for 12 and 24 weeks post-treatment to determine sustained virological response (SVR12 and SVR24), considered to be a cure.

Results

• By treatment week 4, 100% of patients had undetectable HCV RNA viral load (<25 IU/mL).
• The end-of-treatment response rate was also 100%.
• A number of patients 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 patients who achieved SVR and those who relapsed.
• Sofosbuvir + ribavirin was generally safe and well-tolerated.
• 6 people experienced serious adverse events and 2 discontinued treatment due to adverse events.
• No deaths, graft loss, acute or chronic organ rejection, or drug-drug interactions between sofosbuvir and immunosuppressants were reported.
• The most common side effects were fatigue, diarrhea, headache, arthralgia (joint pain), and nausea.
• Anemia was common, with 28% of patients reducing their ribavirin dose and 20% receiving erythropoietin or blood product transfusions.

"High SVR rates were achieved in this difficult-to-treat population," the researchers concluded. "Sofosbuvir + ribavirin was a potent all-oral therapy for treatment of HCV infection following liver transplantation."

5/2/14

Reference

D Samuel, M Charlton, E Gane, et al. Sofosbuvir and ribavirin for the treatment of recurrent hepatitis C infection after liver transplantation: results of a prospective, multicenter study. 49thEuropean Association for the Study of the Liver International Liver Congress (EASL 2014). London, April 9-13, 2014. Abstract P1232.