Published: Nov 6, 2013
By Michael Smith, North American Correspondent, MedPage Today
WASHINGTON -- The advent of new all-oral regimens for hepatitis C (HCV) offers hope to patients who have undergone liver transplant and had the disease recur, a researcher said here.
Patients with hepatitis C who get a new liver universally have a recurrence of the disease in the new organ, according to Michael Charlton, MD, of the Mayo Clinic in Rochester.
Currently approved treatments have "poor tolerance, poor efficacy, severe adverse reactions, and significant interactions with immunosuppression medications," Charlton reported at the annual meeting of the American Association for the Study of Liver Diseases.
But preliminary results from an ongoing study using a novel medication, sofosbuvir, combined with the standard drug ribavirin suggest that those obstacles can be overcome, he said.
The study is "one of the most exciting papers presented today," commented Donald Jensen, MD, of the University of Chicago, who was not involved in the study but who moderated the session at which it was presented.
"It's data where we had poor treatment before this," he told MedPage Today, "and to get 80% cure rates in those patients is incredibly impressive."
He cautioned that the study is small and the results are still preliminary. But with approval of sofosbuvir expected within several weeks, "that's a very impactful study."
Charlton and colleagues are studying 40 patients -- more than 6 months and less than 150 months after transplant -- whose viral infection has recurred.
Most of the patients have high viral loads, genotype 1 HCV, unfavorable genetic variants, and either bridging fibrosis or cirrhosis.
They have been treated for 12 weeks with 400 mg daily of sofosbuvir and escalating doses of ribavirin, adjusted to keep hemoglobin levels as high as possible.
For this analysis, Charlton said, he had data on 39 patients who had completed treatment; all had undetectable virus at the end of therapy.
The primary endpoint of the study is the undetectable virus 12 weeks after the end of treatment (SVR12 ). So far, Charlton has data on 35 patients who had completed 4 weeks of follow-up after therapy.
Of those, 27 (77%) still had undetectable virus or SVR4.
There has been no apparent effect of sofosbuvir on immunosuppressive medications, Charlton reported.
As expected, the ribavirin effect on hemoglobin was marked. Eight of the four patients received epoetin, blood products, or both to compensate and 11 of the 40 had a reduction in ribavirin dose.
There have been six serious adverse events, but all were judged unrelated to the study drugs. Two patients stopped treatment because of adverse events, but there were no deaths, graft losses, or incidents of rejection.
More than a quarter of the patients had grades 3 or 4 lab abnormalities, but they were the type usually associated with ribavirin, including lymphocytopenia and low hemoglobin.
Taken overall, Charlton concluded, the drug combination is safe, well tolerated, and offers a "potential all-oral therapy for treatment of HCV infection following liver transplantation."
On the other hand, a European researcher confirmed that treatment with the current standard of care -- while better than in past years -- remains difficult to deliver and yields poor results.
Current therapy includes pegylated interferon and ribavirin, along with one of two recently approved protease inhibitors, telaprevir and boceprevir, noted Audrey Coilly, MD, of Hôpital Paul Brousse in Villejuif, France, who present results from a separate study.
But in a cohort of 79 recently transplanted HCV-positive patients, the treatment led to SVR12rates of 41% in patients getting telaprevir and in 51% of those on boceprevir, Coilly reported. And those rates were not sustained through 24 weeks -- the SVR24 rates were 27% and 47%, respectively.
A key finding, she said, was that 48% of boceprevir patients stopped treatment early, as did 61% of telaprevir patients.
Charlton reported no conflicts of interest. Coilly reported relationships with Gilead, Bristol Myers Squibb (BMS), Roche, and Novartis.
Their respective co-authors reported various relationships with multiple companies including, but not limited to, Roche, Gilead Sciences, Novartis, Boehringer Ingelheim, Merck, BMS, Janssen, Vertex, Pfizer, Medtronics, Schering-Plough, and Astellas.
Primary source: American Association for the Study of Liver Diseases
Source reference: Charlton M, et al "Sofosbuvir and ribavirin for the treatment of established recurrent Hepatitis C infection after liver transplantation: Preliminary results of a prospective, multicenter study" AASLD 2013; Abstract LB-2.
Additional source: American Association for the Study of Liver Diseases
Source reference:Coilly, A, et al "Sustained virological response after protease inhibitor-based therapy For Hepatitis C recurrence after liver transplantation: A multicentric European experience" AASLD 2013; Abstract 216.