High SVR12 With Ledipasvir/Sofosbuvir + Ribavirin Despite Transplant Status

SAN FRANCISCO, CA—Ledipasvir/sofosbuvir with ribavirin treatment for 12 or 24 weeks in patients with decompensated cirrhosis or recurrent hepatitis C virus (HCV) infection was effective, with low relapse rates, Edward J. Gane, MBChB, MD, from the University of Auckland, Auckland, New Zealand, presented at The Liver Meeting® 2015.

Treatment options for patients with HCV with decompensated cirrhosis or who have undergone liver transplantation are limited. Dr. Gane and colleagues pooled efficacy data from the SOLAR-1 and SOLAR-2 studies, in which 7 groups of patients with HCV genotype (GT) 1 or 4 were randomized to receive 12 or 24 weeks of ledipasvir/sofosbuvir + ribavirin.

These included pre-transplant patients with 1) Child-Pugh-Turcotte (CPT) B or 2) CPT C cirrhosis (n=212); or post-transplant patients with 3) no cirrhosis (fibrosis score F0– F3), 4) CPT A, 5) CPT B or, 6) CPT C cirrhosis, or 7) fibrosing cholestatic hepatitis (FCH) (n=455).

At 12 weeks after treatment, researchers measured sustained virologic response (SVR12), relapse, and change from baseline in CPT and MELD scores.

The investigators found that treatment with ledipasvir/sofosbuvir + ribavirin "resulted in high SVR12 rates in HCV patients with advanced liver disease, irrespective of transplantation status." In patients with HCV GT1, no difference was observed in SVR rates between 12 and 24 weeks of treatment. Among those with HCV GT4, there were too few patients "for meaningful comparisons," they noted.

"Among patients with cirrhosis, virologic response was associated with improvements in MELD and CPT scores, largely reflecting improvements in synthetic function," Dr. Gane added.

The SVR12 rates at post-treatment week 12 and 24 for the pre-transplant patients were 86% and 92% for CPT B and 84% and 81% for CPT C, respectively. For post-transplant patients, these rates were 95% and 99% for F0– F3, 97% and 97% for CPT A, 90% and 94% for CPT B, 50% and 78% for CPT C, and 100% and 100% for FCH, they found.

Relapse rates were highest in the post-transplant CPT C group; overall, 3 of 7 patients (43%) had a relapse at 12 weeks and 1 of 8 (13%) at 24 weeks. Among these 4 patients, 3 were GT1 and 1, GT4.

Among CPT B patients (n=187), 40% improved to CPT A at follow-up week 24; 2% had worsened to CPT C and 58% had no change. Among CPT C patients (n=77), 12% improved to CPT A, 64% to CPT B, and 24% had no change.

At follow-up Week 24, the MELD score change from baseline in CPT B/C patients who achieved SVR12 showed a 56% improvement among those with a baseline MELD of less than 15 (n=199), while 26% worsened; among those with baseline MELD of 15 or higher (n=72), 76% improved and 11% worsened, they noted. 

"In patients with FCH, virologic response was associated with rapid and sustained improvements in liver function as assessed by MELD score," Dr. Gane stated. "Most patients had total bilirubin, γ-glutamyltransferase, alanine aminotransferase, and albumin levels within normal range at follow-up Week 24."

"Longer follow-up will determine whether SVR in patients with decompensated HCV cirrhosis is associated with improvement in patient and transplant-free survival," the study concluded.

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