title: Combination therapy with silibinin, pegylated interferon and ribavirin in a patient with hepatitis C virus genotype 3 reinfection after liver transplantation: a case report.
abstract: BACKGROUND
  Hepatitis C virus reinfection occurs universally after liver transplantation with accelerated cirrhosis rates of up to 30% within 5 years after liver transplantation. Management of hepatitis C virus reinfection is complicated by drug interactions and pre-treatment. Dual antiviral therapy with pegylated interferon and ribavirin only reaches sustained virological response rates of approximately 30% after liver transplantation. With the approval of the viral NS3/4A protease and NS5B ribonucleic acid -dependent ribonucleic acid polymerase inhibitors, combination therapy offers new therapeutic options resulting in considerably higher sustained virological response rates in the non-transplant setting. However, silibinin has also shown potent antiviral activity in non-responders to dual therapy.
  
  
  METHODS
  We report the first case of antiviral therapy with pegylated interferon and ribavirin in combination with silibinin post-liver transplantation in a 50-year-old Caucasian man with genotype 3 reinfection with prior non-response.Silibinin was administered at a dose of 20mg/kg/day intravenously for 2 weeks and continued orally for 47 weeks in combination with a 48-week pegylated interferon and ribavirin therapy (180μg/week and 800mg/day), which was started on day 8. Pegylated interferon and ribavirin doses were adapted to 135μg/week and 600mg/day. After 4 weeks of therapy, the viral load declined 6 log10 and became undetectable in week 6, resulting in a sustained virological response 24 weeks after the end of therapy.In general, antiviral therapy was well tolerated. Side effects included pruritus and anaemia leading to erythropoietin therapy.
  
  
  CONCLUSIONS
  Combination therapy with pegylated interferon, ribavirin and silibinin resulted in sustained virological response 24 weeks after the end of therapy in a patient reinfected with hepatitis C virus genotype 3 who was a prior non-responder after liver transplantation. Silibinin therapy may offer a new therapeutic option for patients reinfected with non-genotype 1 hepatitis C virus who have had a liver transplanted and are non-responders.
authors.forename: Johanna
authors.initials: J
authors.lastname: Knapstein
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Wörns
authors.forename: Peter R
authors.initials: PR
authors.lastname: Galle
authors.affiliation: I, Department of Internal Medicine, Johannes Gutenberg-University, Langenbeckstraße 1, 55131 Mainz, Germany. tim.zimmermann@unimedizin-mainz.de.
authors.forename: Tim
authors.initials: T
authors.lastname: Zimmermann
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016898:Interferon-alpha / Q000627:therapeutic use; D008111:Liver Function Tests; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D012254:Ribavirin / Q000627:therapeutic use; D000077385:Silybin; D012838:Silymarin / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012838:Silymarin; D011092:Polyethylene Glycols; D012254:Ribavirin; D000077385:Silybin; C100416:peginterferon alfa-2a