title: Safety and efficacy of peginterferon-α2a plus ribavirin treatment in renal transplant recipients with chronic hepatitis C.
abstract: OBJECTIVE
  Interferon (IFN)-based therapy in chronic hepatitis C virus (HCV)-infected renal transplant (RT) recipients has been associated with a high risk of acute allograft rejection (AAR) and poor efficacy. We assessed the safety and efficacy of PegIFNα-2a and ribavirin (RBV) combination therapy in HCV-infected RT recipients.
  
  
  METHODS
  Thirty-two adult RT recipients of >12-month duration, infected with HCV genotypes 1 (62.5%) and 4 (37.5%), and significant fibrosis (Metavir ≥ F2) were recruited in an open-label trial with PegIFNα-2a 135-180 μg/week, plus RBV 200-1200 mg/day for 48 weeks, based on the estimated glomerular filtration rate. Safety assessments were performed weekly for 4 weeks, 2-weekly for 8 weeks, and 6-weekly for 36 weeks. Study end points were sustained virologic response (SVR) or development of AAR. Allograft biopsies were performed for 20% increase in creatinine from pretreatment levels, or optionally at week 12 on surveillance protocol. Renal safety was compared with matched untreated historical controls (n=31).
  
  
  RESULTS
  None of the treated patients showed AAR when biopsied for raised creatinine (12.5%) or during surveillance (37.5%), with incremental and sustained creatinine increases occurring in 6.3% of treated patients and 16.1% of untreated controls (p=0.148), by week 72 assessment. Mean pretreatment and end-of-assessment creatinine in treated patients remained similar (106.8 ± 32.0 vs. 113.4 ± 62.8, respectively; p=0.140), while levels increased significantly in the controls (106.6 ± 35.6 vs. 142.5 ± 93.0, respectively; p=0.013). Rapid, early virologic response (EVR) and SVR occurred in 12.5%, 56.3%, and 37.5% of cases, respectively. SVR was similar in both genotypes (p=1.000). PegIFN and RBV dose reductions were required in 34.4% and 78.1%, respectively; discontinuation was required in 12.5%. Binary logistic regression identified only EVR (OR, 20.4; 95% CI: 2.2-192.6; p=0.008) as an independent predictor of SVR.
  
  
  CONCLUSIONS
  PegIFN/RBV therapy is not associated with AAR in RT recipients at low risk for rejection but has modest efficacy in the treatment of HCV.
authors: Department of Gastroenterology, Riyadh Military Hospital, Riyadh, Saudi Arabia. sanaifa@ngha.med.sa
authors: Faisal M
authors: FM
authors: Sanai
authors: Dujana
authors: D
authors: Mousa
authors: Abdallah
authors: A
authors: Al-Mdani
authors: Ghada
authors: G
authors: Al-Shoail
authors: Hamad
authors: H
authors: Al-Ashgar
authors: Khalid
authors: K
authors: Al Meshari
authors: Ahmed
authors: A
authors: Al-Qahtani
authors: Mayssa
authors: M
authors: Saadeh
authors: Khalid I
authors: KI
authors: Bzeizi
authors: Hassan
authors: H
authors: Aleid
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a