Daclatasvir-based Tx Shows High Viral Clearance in Liver Transplant Patients
BOSTON, MA—At The Liver Meeting® 2016, researchers reported "high efficacy and an excellent safety profile" for direct-acting antiviral (DAA) combinations with daclatasvir (DCV) among transplanted patients with hepatitis C virus (HCV) infection.
Prior to the new DAA era, patients with HCV who have undergone a liver transplant showed a poor prognosis. An Italian named patient program (NPP) was launched in 2013-2014 based on the availability of DAA combinations. "NPP was first granted to liver transplanted patients with advanced disease, if life expectancy was shorter than 12 months due to severe HCV recurrence or cholestatic hepatitis," explained Raffaella Lionetti, from POIT, IRCCS Lazzaro Spallanzani, Rome, Italy.
The aim of the study (n=94) was to evaluate real-life evidence of virologic efficacy in liver transplant patients as measured by sustained virologic response (SVR12), the safety profile of DAAs combinations and the clinical outcome. Certain liver transplant patients with HCV were selected and were included in NPP; they were treated with daclatasvir + sofosbuvir or simeprevir.
Of the total enrolled patients, the majority (84.1%) were infected with HCV genotype 1. About three-quarters (76.6%) of patients were exposed to prior interferon (IFN) therapy and ribavirin. Eighty-eight patients received daclatasvir + sofosbuvir ± ribavirin and 6 patients received daclatasvir + simeprevir for 24 weeks.
SVR data was available in 87 patients. The data showed undetectable HCV RNA in 50% of patients at Week 4, in >75% by Week 8, and in 97% at Week 12. "SVR12 and SVR24 did not differ and was overall 88.2%," stated Dr. Lionetti. For patients with genotype 3, however, SVR12 was lower (75%) consistent with existing literature.
Five patients in the daclatasvir + sofosbuvir group died and 1 patient in the daclatasvir + sofosbuvir + ribavirin group was lost to follow-up.
Patients with severe hepatic impairment (Child-Pugh A vs. C) saw a significant decrease in SVR12 and SVR24. However, patients with mild impairment exhibited similar virologic outcomes. Renal function was observed to worsen during therapy and at end of treatment.
Of the 53 patients who received ribavirin, all but 1 experienced SVR, indicating a significant odds ratio (OR 15.1; P<0.012). The majority of adverse events were related to the addition of ribavirin and related anemia although ribavirin at lower doses did seem to improve SVR.
"A better SVR could be reached by treating patients in an earlier disease stage and with preserved liver function," concluded Dr. Lionetti.