Efficacy of Sofosbuvir and Daclatasvir in Patients with Fibrosing Cholestatic Hepatitis C After Liver Transplantation
Résumé
BACKGROUND & AIMS: Fibrosing cholestatic hepatitis (FCH) is a life-threating disorder that develops in patients with recurrent hepatitis C virus (HCV) infection after liver transplantation. Until recently, therapeutic options have been limited. We evaluated the efficacy and safety of sofosbuvir- and daclatasvir-based regimens. METHODS: We analyzed data from 23 patients with FCH who participated in a prospective cohort study in France and Belgium of the effects of anti-viral agents in patients with recurrence of HCV infection after liver transplantation, from October 2013 through April 2014. Most of the patients had genotype 1 infections that had not responded to previous treatment; 4 were also infected with HIV. Eight patients (37%) had ascites and 15 (65%) had bilirubin levels \textgreater100 mmol/L; their median serum level of HCV-RNA was 7 log IU/mL. The median time between transplantation and treatment initiation was 5 months. Subjects were given either sofosbuvir and daclatasvir (n=15) or sofosbuvir and ribavirin (n=8), for 24 weeks. The primary outcome was complete clinical response (survival without re-transplantation, bilirubin \textless 34 μmol/L, and no ascites or hepatic encephalopathy 36 weeks after treatment began). RESULTS: All patients survived, without re-transplantation, until week 36. Rapid and dramatic improvements in clinical status were observed. The patients' median bilirubin concentration decreased from 122 μmol/L at baseline to a normal value at week 12 of treatment. Twenty-two patients (96%) had a complete clinical response at week 36. Despite the low rate of rapid virologic response, 22 patients (96%) achieved a sustained virologic response at week 12 (SVR12). The only relapse of HCV infection occurred in a patient with HIV infection who received sofosbuvir and ribavirin. Tolerance was satisfactory, with no grade 3 or 4 adverse events related to sofosbuvir or daclatasvir and no significant interactions among drugs. CONCLUSION: Sofosbuvir therapy with daclatasvir or ribavirin leads complete clinical responses and high rates of SVR12 in most patients with recurrence of HCV infection and FCH following liver transplantation. ClinicalTrial.gov no: NCT01944527