Daclatasvir and sofosbuvir treatment of decompensated liver disease or post‐liver transplant hepatitis C virus recurrence in patients with advanced liver disease/cirrhosis in a real‐world cohort

Abstract

We report the findings of an early access program providing treatment for chronic hepatitis C virus infection (any genotype) with daclatasvir and sofosbuvir with/without ribavirin to patients with Child‐Pugh class C cirrhosis or prior liver transplant recipients with recurrent hepatitis C virus infection and advanced fibrosis/cirrhosis. Patients had <12‐month life expectancies per the local investigator. Patients received daclatasvir 60 mg and sofosbuvir 400 mg once daily, with/without ribavirin, for 24 weeks. Sustained virologic response (SVR) at posttreatment week 12 (SVR12) was measured. Assessments adhered to local standards. One patient (prior Child‐Pugh class C who improved to class B) enrolled by exemption was included in the overall data but not the class C cohort efficacy/safety data. Of the 77 treated patients, including 62 liver transplant recipients (genotype 1, n = 43, 69%; genotype 3, n = 16, 26%) and 14 patients with Child‐Pugh class C cirrhosis (genotype 1, n = 4, 29%; genotype 3, n = 10, 71%), 63 (82%) completed treatment. SVR12 rates by modified intention‐to‐treat analysis (excluding nonvirologic failures lost to follow‐up and withdrawal [consent/no reason]) in the overall, liver transplant, and Child‐Pugh class C cohorts were 84% (n = 64/76), 90% (n = 56/62), and 62% (n = 8/13), respectively. Rates increased to 96% (n = 64/67), 97% (n = 56/58), and 89% (n = 8/9), respectively, in patients with available virologic data (including early discontinuations); 22/23 patients with genotype 3 (96%) achieved SVR12. Single cases of virologic nonresponse and relapse (both in liver transplant recipients with genotype 1) and viral breakthrough (Child‐Pugh class C; genotype 3) occurred. Six patients died, 10 had adverse events leading to discontinuation, and 30 experienced serious adverse events. Conclusion: Daclatasvir plus sofosbuvir, with/without ribavirin, provided high SVR12 rates and was generally well tolerated in patients with life‐threatening disease and high unmet needs. (Hepatology Communications 2018;2:354‐363)

Viral Hepatitis C Therapy: Pharmacokinetic and Pharmacodynamic Considerations: A 2019 Update

“…Liver transplant recipients with HCV recurrence obtained an SVR rate of 94% following SOF/DCV/RBV for 12 weeks. Similar results were achieved in other studies with liver transplant patients [54, 110, 162]. Efficacy rates for SOF/LDV varying from 50 to 100% were seen in HCV recurrent liver transplant recipients following the fixed-dose combination of SOF/LDV [69, 124, 146].…”

“…In several studies, concomitant therapy with RBV resulted, as previously described [52], in anemia and leukopenia [47, 51, 53–57]. Following an AE, ≤ 7% of the patients discontinued treatment with SOF/DCV, with the exception of patients with a life expectancy of less than 12 months due to decompensated cirrhosis or recurrence of HCV following a liver transplant, in whom 10% and 18%, respectively, discontinued therapy due to an AE [54].…”

“…After treatment with SOF/DCV combination therapy for 12 or 24 weeks (according to disease severity), SVR12 rates of 50–100% [47–50, 53–57, 112] were reached in CP-A/B/C patients. Lower rates of SVR12 (< 90%) were obtained in the studies with small sample sizes [54]. Accordingly, SOF/DCV is a treatment option for CP-A/B/C patients without any dose adjustments needed (see Table 4).…”

B.A.R.C.O.S. (Brazilian Argentine Hepatitis C Collaborative Observational Study): Effectiveness and clinical outcomes of HCV treatment with daclatasvir and sofosbuvir with or without ribavirin

“…Similar trends have also been described in the United States where the SOF/DCV combination was demonstrated to be effective in patients with advanced liver disease and post‐LT recurrence. In 77 treated patients, SVR rates varied between 84% and 96% according to baseline patient characteristics . In the HCV TARGET database, one of the most important cohorts of HCV‐treated subjects, no patient receiving SOF/DCV was included .…”

Safety and efficacy of sofosbuvir/ledipasvir and sofosbuvir/daclatasvir in the treatment of hepatitis C in patients with decompensated cirrhosis

“…Similarly, Kwo et al . [14] also demonstrated that treatment with SOF/DCV, with or without RBV, resulted in high SVR12 rates (an overall 84%) and was generally well-tolerated in this category of patients. Moreover, Ippolito et al ., [15] reported SVR12 rates of 97.6% in patients with advanced fibrosis ( n = 575) and SVR12 rates of 93.6–100% in patients with cirrhosis ( n = 2037) and suggested that DAAs can be used in patients with advanced cirrhosis.…”