Multicenter experience using simeprevir and sofosbuvir with or without ribavirin to treat hepatitis C genotype 1 in patients with cirrhosis

Abstract

Interferon (IFN)-free regimens are needed to treat hepatitis C virus (HCV) infection. Combined simeprevir (SMV) and sofosbuvir (SOF) with or without ribavirin (RBV) results in high sustained virological response (SVR) rates along with minimal adverse events (AEs) in patients with hepatitis C genotype 1 (HCV GT1). The aim of this study was to report on the virological response, safety, and tolerability of SOF and SMV with or without RBV in compensated and decompensated patients with cirrhosis with HCV GT1 infection. Patients treated with standardized clinical protocol utilizing SMV1SOF with or without RBV at three transplant centers were retrospectively reviewed. A total of 119 patients (61% male, 87% white, 69% subtype 1a, 30% Child-Pugh-Turcott [CPT]-B liver cirrhosis [LC], and 82% were treatment experienced) received treatment and were followed for a median of 38 weeks (range, 12-58). Sustained virological response (SVR) at week 12 (SVR12) was achieved in 78% (92 of 118) of patients (95% confidence interval: 69-85). Lower pretreatment Model for End Stage Liver Disease (MELD) score was a predictor of SVR12 (P 5 0.018). Baseline viral load, previous treatment status, RBV use, or GT1 subtype did not impact SVR 12. The majority of patients with SVR12 showed stability or improvement in MELD score. Treatment was very well tolerated with mild degrees of AEs. Conclusions: The regimen of SMV1SOF with or without RBV for 12 weeks was very well tolerated and resulted in high SVR12 rates (78%) in HCV GT1 patients with LC. SVR12 was inversely related to pretreatment MELD. SVR12 had favorable short-term impact on MELD score. Long-term impact on disease stability is yet to be determined. Longer treatment duration or the use of different regimen may still be needed in this population. (HEPATOLOGY 2015;62:1004-1012 A pproximately 3.4-4.9 million Americans are chronically infected with hepatitis C virus (HCV) and are at risk of developing cirrhosis, hepatocellular carcinoma (HCC), or both. Both decision modeling studies and U.S. veterans national studies estimated that 18%-25% of HCV-infected patients will have cirrhosis at time of diagnosis. That estimate will most likely reach a peak of 45% in 2020, leading to a progressive increase in the rates of hepatic decompensation and HCC in the next two decades.1 As a result of this, HCV infection is the leading indication for liver transplantation (LT) worldwide.

Ideal oral combinations to eradicate HCV: The role of ribavirin

“…Based on data with other IFN-free combinations with SOF, adding daily weight-based RBV (1000 or 1200 mg in patients <75 kg or ≥75 kg, respectively) could be recommended with SOF and SMV in genotype 1 patients with compensated cirrhosis. The efficacy and safety of SOF plus SMV for 12 or 24 weeks with or without RBV in genotype 1 patients with decompensated cirrhosis has been evaluated in several real-life cohorts [44][45][46]. These studies suggest that the addition of RBV may increase the SVR12 rates in this population [46].…”

“…The efficacy and safety of SOF plus SMV for 12 or 24 weeks with or without RBV in genotype 1 patients with decompensated cirrhosis has been evaluated in several real-life cohorts [44][45][46]. These studies suggest that the addition of RBV may increase the SVR12 rates in this population [46].…”

Diagnostics in hepatitis C: The end of response-guided therapy?

“…However, patients with undetectable HCV RNA at week 4 had only slightly higher SVR compared to those with detectable HCV RNA at this time point (86% vs. 76%) [67] (Table 3). Other studies support the notion that on-treatment HCV RNA alone may not be a good predictor of SVR with this DAA regimen [40,[97][98][99].…”

Does SVR Prevent Transplant in HCV?

“…Retrospective data on the off-label use of simeprevir with sofosbuvir in decompensated cirrhotics, largely from the period when these were the only DAA medications available in the USA, revealed response rates ranging from 73-91 % [40,44,45], though reports of cholestatic liver injury with this regimen preclude recommending the use of this regimen in decompensated patients [42,43].…”