title: Treatment of hepatitis C virus recurrence after transplantation with sofosbuvir/ledipasvir: The role of ribavirin.
abstract: BACKGROUND
  Hepatitis C virus (HCV) recurrence after liver transplantation (LT) used to be a serious problem in the era of interferon-based treatment. Since the introduction of modern directly acting antivirals, treatment has become easier and shorter. According to published data, in the natural course of hepatitis C infection the duration of antiviral treatment with sofosbuvir (SOF) and ledipasvir (LDV) may be shortened to 12 instead of 24 weeks, using ribavirin (RBV) in addition. Furthermore, the question of whether or not RBV is really necessary, in a 12-week SOF/LDV treatment in the post-transplant setting, is still unanswered.
  
  
  METHODS
  At our institution, 100 liver transplant patients with HCV recurrence underwent interferon-free SOF-based treatment. A total of 51 patients received SOF/LDV with or without RBV. Twenty-nine HCV genotype 1 or 4 patients with histologically proven stage 0-2 fibrosis were treated with SOF/LDV for 12 weeks; another 22 patients with advanced fibrosis (stage 3-4) either received SOF/LDV plus weight-adjusted RBV or prolonged treatment for 24 weeks.
  
  
  RESULTS
  End of treatment response and sustained virological response (SVR) were achieved in 100% of the 51 patients, irrespective of the treatment group. Patients with prolonged treatment duration or with RBV developed significantly more adverse events (AEs) compared to the SOF/LDV group: 19 (86.4%) vs 8 (27.6%), P<.001. One of the predominant and most relevant AEs was the development of anemia in 43.1% of 10 patients receiving RBV, which was a significant result (P<.001). RBV co-medication had to be reduced in 11 (55%) patients and then stopped in 8 (40%) patients because of AEs. No significant difference was observed among the groups regarding kidney function.
  
  
  CONCLUSIONS
  The SOF/LDV combination is a reliable therapy of recurrent HCV infection after LT. It is easy to administer and to achieve SVR in immunocompromised patients without interactions with immunosuppressive medications. Considering the high rate of AEs, frequent discontinuation of RBV treatment, and the 100% SVR, the use of RBV as co-medication in a 12-week SOF/LDV regimen does not seem to be justified after LT.
authors.affiliation: General, Visceral and Transplant Surgery, Charité Campus Virchow, Berlin, Germany.
authors.forename: Brigitta
authors.initials: B
authors.lastname: Globke
authors.affiliation: General, Visceral and Transplant Surgery, Charité Campus Virchow, Berlin, Germany.
authors.forename: Nathanael
authors.initials: N
authors.lastname: Raschzok
authors.affiliation: General, Visceral and Transplant Surgery, Charité Campus Virchow, Berlin, Germany.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Teegen
authors.affiliation: General, Visceral and Transplant Surgery, Charité Campus Virchow, Berlin, Germany.|General, Visceral, Thoracic and Vascular Surgery, Charité Campus Mitte, Berlin, Germany.
authors.forename: Johann
authors.initials: J
authors.lastname: Pratschke
authors.affiliation: Gastroenterology and Hepatology, Charité Campus Virchow, Berlin, Germany.
authors.forename: Eckart
authors.initials: E
authors.lastname: Schott
authors.affiliation: General, Visceral and Transplant Surgery, Charité Campus Virchow, Berlin, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Eurich
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D005449:Fluorenes / Q000494:pharmacology / Q000627:therapeutic use*; D016174:Hepacivirus / Q000187:drug effects* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use*; D000069474:Sofosbuvir / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; D007166:Immunosuppressive Agents; C586541:ledipasvir; D012254:Ribavirin; D000069474:Sofosbuvir
keywords: DAAs; HCV recurrence; ledipasvir; liver transplantation; sofosbuvir