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Twelve weeks of treatment yielded high efficacy rates in hepatitis C (HCV) patients with advanced liver disease or recurrent HCV after transplant.
by Michael Smith
North American Correspondent, MedPage Today
VIENNA -- In hepatitis C virus (HCV) patients with advanced liver disease or recurrent HCV after transplant, 12 weeks of treatment yielded high efficacy rates, a researcher said here.
Efficacy did not differ greatly among patients randomly assigned to 12 or 24 weeks of treatment with the fixed-dose combination of ledipasvir/sofosbuvir (Harvoni) given with ribavirin, according to Michael Manns, MD, of Hannover Medical School in Hannover, Germany.
And the combination was generally well-tolerated -- an important consideration among the seriously ill patients in the so-called SOLAR-2 trial, Manns told reporters here at the annual meeting of the European Association for the Study of the Liver.
The study evaluated the safety and efficacy of the therapy in patients with Child-Pugh scores of B and C either pre- or post-transplant, or in those whose disease had recurred after transplant but who were Child-Pugh A or had fibrosis scores of F0 through F3.
The goal was to compare outcomes with 12 weeks of therapy with those after 24 weeks -- the recommended duration for such patients in Europe, Manns said.
For most patients with conditions similar to those in the trial, Manns said, "I would feel comfortable treating for 12 weeks."
But most of the 328 patients had genotype 1 disease, and the handful of patients in the study with genotype 4 HCV did not do as well, he noted. For those patients, he said, he would continue to aim for 24 weeks of therapy "depending on tolerability."
What to do with the difficult-to-treat patients in the study is a tough question, commented Markus Peck-Radosavljevic, MD, of the Medical University of Vienna and current Secretary General of EASL.
On one hand, Peck-Radosavljevic told MedPage Today, the study does show that the treatment "is not endangering" the patients and can lead to cures in most cases.
But on the other hand, he said, "there might be a point where you don't do them a favor by making them virus-free."
It could happen, he said, that treatment might cure a patient of HCV, leaving him or her ineligible for a transplant but still with a seriously damaged liver.
In many cases, he said, it might be better to go ahead with a transplant and count on being able to cure recurrent HCV afterward.
Patients in the trial, Manns said, had either genotype 1 or 4 and were stratified into six groups:
- Patients without transplant and either Child-Pugh B or Child-Pugh C cirrhosis -- groups 1 and 2
- Patients with recurrent HCV after liver transplantation and either without cirrhosis or with Child-Pugh A, B, or C cirrhosis -- groups 3 through 6
The endpoint of the study was sustained virologic response 12 weeks after the end of treatment (SVR12).
Overall, Manns reported, post-transplant patients without fibrosis or with Child-Pugh A status did equally well with 12 or 24 weeks of therapy -- SVR12 rates were 95% and 98%, respectively.
Patients with Child-Pugh B or C cirrhosis, regardless of transplant status, did less well but, again, treatment duration seemed to have little effect -- 85% with SVR12 at 12 weeks and 88% at 24 weeks, Manns reported.
Differences appeared when the patients were broken down by genotype, however.
Among patients with genotype 1 disease, 12- and 24-week SVR12 rates were 96% and 98% if they had low fibrosis scores or Child-Pugh A cirrhosis, and 88% and 89%, respectively, for those with Child-Pugh B or C cirrhosis.
The 18 patients with genotype 4 and less advanced liver damage had SVR12 rates of 91% and 100% after 12 and 24 weeks of therapy, respectively.
But among the 14 patients with genotype 4 and Child-Pugh B and C cirrhosis, 12- and 24-week SVR12 rates were 57% and 86%, respectively.
Most patients reported at least one adverse event, with rates of between 92% and 95%, Manns said, but serious adverse events were much less common -- reported by between 14% and 28% of patients, with more seen among those with more advanced disease.
There were no treatment-related adverse events in patients without cirrhosis and nine among those with cirrhosis, including five reports of anemia and one each of falling, vomiting, diarrhea, and hyperbilirubinemia.
Although there were 10 deaths, none was considered related to treatment, Manns said.
The study was supported by Gilead Sciences. Manns disclosed relevant relationships with AbbVie, BI, BMS, Gilead, Janssen, Merck, Novartis, Roche, Idenix, and GSK. Some authors are employees of Gilead.
Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College
Primary Source: European Association for the Study of the Liver
Source Reference: Manns M, et al "Ledipasvir/sofosbuvir with ribavirin is safe and efficacious in decompensated and post liver transplantation patients with HCV infection: Preliminary results of the prospective SOLAR 2 trial" EASL 2015; Abstract G02.