title: Ribavirin priming improves the virological response to antiviral treatment in transplanted patients with recurrent hepatitis C: a pilot study.
abstract: BACKGROUND
  Patients with hepatitis C recurrence after liver transplantation represent a clinical challenge. Antiviral treatment in transplant patients has usually poor tolerability and limited efficacy, with a mean sustained virological response (SVR) of 30%. Our pilot study was aimed at evaluating whether 8-week ribavirin pre-treatment could increase either adherence or antiviral effect of a 48-week combination therapy.
  
  
  METHODS
  Ribavirin pre-treatment (8 weeks) was started with 600 mg daily and increased to 10.4 mg/kg/day. After pre-treatment, 1.5 μg/kg/week pegylated interferon-α2b was added for 48 additional weeks of combination therapy. Blood count, liver function tests and plasma HCV-RNA were examined monthly. Ribavirin plasma concentrations were determined by HPLC.
  
  
  RESULTS
  Thirteen patients (mean age 53±2 years, 11 males) were treated: eight were HCV genotype 1/4; five were genotype 2/3. The median baseline HCV RNA level was 6.5 log(10) (range 5.84-7.42 log(10)). During ribavirin pre-treatment the median HCV RNA levels decreased significantly (5.7 log(10) ; P=0.023). During combination therapy 6/13 (46%) patients exhibited a rapid virological response (RVR) and 10/13 (77%) patients a complete early virological response, two were non-responders. A decline of 0.5 log(10) HCV RNA during pre-treatment predicted RVR. SVR occurred in six patients (46%): four were genotype 2/3. Stable ribavirin dose reduction was required in only two patients (15%) in whom transient interferon reduction was also required.
  
  
  CONCLUSIONS
  This proof-of-concept study indicates that ribavirin pre-treatment increased the tolerability of the antiviral treatment, and improved its efficacy in liver transplant patients. Moreover, the degree of HCV RNA decline during pre-treatment allowed one to predict on-treatment response.
authors: II Gastroenterologia, Policlinico Umberto I, Sapienza, Università di Roma, Rome, Italy. Manuela.merli@uniroma1.it
authors: Manuela
authors: M
authors: Merli
authors: Valerio
authors: V
authors: Giannelli
authors: Federica
authors: F
authors: Gentili
authors: Michela
authors: M
authors: Giusto
authors: Maurizio
authors: M
authors: Simmaco
authors: Luana
authors: L
authors: Lionetto
authors: Stefano G
authors: SG
authors: Corradini
authors: Elisa
authors: E
authors: Biliotti
authors: Adolfo F
authors: AF
authors: Attili
authors: Massimo
authors: M
authors: Rossi
authors: Gloria
authors: G
authors: Taliani
mesh_terms: D000740:Anemia / Q000209:etiology; D000998:Antiviral Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000627:therapeutic use; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006526:Hepatitis C / Q000188:drug therapy* / Q000601:surgery / Q000821:virology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011292:Premedication; D012008:Recurrence; D012254:Ribavirin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D012254:Ribavirin; D007372:Interferons