Sofosbuvir plus daclatasvir for post-transplant recurrent hepatitis C: potent antiviral activity but no clinical benefit if treatment is given late

Dig Liver Dis. 2014 Oct;46(10):923-7. doi: 10.1016/j.dld.2014.06.004. Epub 2014 Jul 3.

Abstract

Background: We evaluated efficacy and safety of sofosbuvir and daclatasvir±ribavirin in liver transplant recipients with severe recurrent hepatitis C.

Methods: Patients included in an international compassionate use programme for treatment with sofosbuvir and daclatasvir±ribavirin for 24 weeks were prospectively studied. Serum hepatitis C virus RNA was measured at treatment weeks 4, 12, and 24 and during follow-up at weeks 4, 8, and 12.

Results: Twelve patients (3 with fibrosing cholestatic hepatitis and 9 with cirrhosis; median model for end-stage liver disease score 20) received sofosbuvir 400mg/day+daclatasvir 60mg/day, and 6 patients (50%) also received ribavirin 200-800mg/day. Nine patients completed 24 weeks of treatment (75%), and all had undetectable hepatitis C virus RNA at week 24; 3 patients died (25%, liver failure, gastrointestinal bleeding and sepsis); 4 patients experienced severe liver disease-related adverse events. Post-treatment hepatitis C virus RNA was available for 5 patients (week 8, n=2; week 4, n=3) and was undetectable in all cases. Mean Child-Pugh score and albumin level improved significantly at week 24. No changes in immunosuppressant doses were needed.

Conclusion: All-oral sofosbuvir plus daclatasvir combination shows high virological efficacy in liver transplant recipients and does not interact with immunosuppressants. All adverse events were unrelated to study drugs. These data strongly suggest that this combination must be initiated before decompensation.

Keywords: Cholestatic hepatitis; Cirrhosis; Daclatasvir; Direct antiviral agents; Disease recurrence; HCV; MELD; Sofosbuvir.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use*
  • Carbamates
  • Compassionate Use Trials
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / surgery
  • Humans
  • Imidazoles / therapeutic use*
  • Liver Transplantation*
  • Male
  • Middle Aged
  • Prospective Studies
  • Pyrrolidines
  • Recurrence
  • Severity of Illness Index
  • Sofosbuvir
  • Treatment Outcome
  • Uridine Monophosphate / analogs & derivatives*
  • Uridine Monophosphate / therapeutic use
  • Valine / analogs & derivatives

Substances

  • Antiviral Agents
  • Carbamates
  • Imidazoles
  • Pyrrolidines
  • Uridine Monophosphate
  • Valine
  • daclatasvir
  • Sofosbuvir