title: Risk for immune-mediated graft dysfunction in liver transplant recipients with recurrent HCV infection treated with pegylated interferon.
abstract: OBJECTIVE
  Patients with recurrent hepatitis C virus infection treated with pegylated interferon (PEG) after liver transplantation can develop severe immune-mediated graft dysfunction (IGD) characterized by plasma cell hepatitis or rejection.
  
  
  METHODS
  We conducted a multicenter case-control study of 52 liver transplant recipients with hepatitis C to assess the incidence of, risk factors for, and outcomes of PEG-IGD. Data from each patient were compared with those from 2 matched patients who did not develop PEG-IGD (n = 104). We performed a multivariate analysis of risk factors and analyzed treatment and outcomes of graft dysfunction subtypes.
  
  
  RESULTS
  Overall incidence of PEG-IGD during a 10-year study period was 7.2%. Risk factors included no prior PEG therapy (odds ratio = 5.3; P < .0001), therapy with PEGα-2a (odds ratio = 4.7; P = .03), and immune features (mainly plasma cell hepatitis) on pre-PEG therapy liver biopsies (odds ratio = 3.9; P = .005). The PEG-IGD group had lower long-term patient (61.5% vs 91.3% of controls) and graft (38.5% vs 85.6% of controls) survival and higher rates of retransplantation (34.6% vs 6.7% of controls) (all, P < .0001), without increases in sustained virologic response. Variables associated with increased mortality included acute rejection as the PEG-IGD sub-type (hazard ratio [HR] = 2.4; P = .002), a high level of alkaline phosphatase at PEG initiation (HR = 1.003; P = .005), and lack of a sustained virologic response (HR = 3.3; P = .04). Variables associated with graft failure included a high level of alkaline phosphatase at PEG initiation (HR = 1.002; P = .04) and lack of a sustained virologic response (HR = 2.1; P = .04).
  
  
  CONCLUSIONS
  PEG-IGD has high morbidity and mortality and is not associated with increased rates of virologic response. It is important to avoid PEG therapy in liver transplant recipients with specific clinical, biochemical, and histologic risk factors for PEG-IGD.
authors.affiliation: Northwestern University Feinberg School of Medicine, Northwestern Memorial Hospital, Chicago, Illinois 60611, USA. j-levitsky@northwestern.edu
authors.forename: Josh
authors.initials: J
authors.lastname: Levitsky
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Fiel
authors.forename: John P
authors.initials: JP
authors.lastname: Norvell
authors.forename: Edward
authors.initials: E
authors.lastname: Wang
authors.forename: Kymberly D
authors.initials: KD
authors.lastname: Watt
authors.forename: Michael P
authors.initials: MP
authors.lastname: Curry
authors.forename: Sumeet
authors.initials: S
authors.lastname: Tewani
authors.forename: Timothy M
authors.initials: TM
authors.lastname: McCashland
authors.forename: Maarouf A
authors.initials: MA
authors.lastname: Hoteit
authors.forename: Abraham
authors.initials: A
authors.lastname: Shaked
authors.forename: Samuel
authors.initials: S
authors.lastname: Saab
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Chi
authors.forename: Amy
authors.initials: A
authors.lastname: Tien
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Schiano
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D005260:Female; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects*; D016031:Liver Transplantation / Q000009:adverse effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011092:Polyethylene Glycols / Q000009:adverse effects*; D055031:Primary Graft Dysfunction / Q000209:etiology* / Q000473:pathology; D011994:Recombinant Proteins / Q000009:adverse effects; D012008:Recurrence; D012307:Risk Factors
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a