title: Successful treatment of fibrosing cholestatic hepatitis after liver transplantation.
abstract: BACKGROUND
  A minority of liver transplant (OLT) recipients with hepatitis C virus (HCV) develop fibrosing cholestatic hepatitis (FCH), a severe form of HCV recurrence associated with early graft failure and death. There are few reports of successful salvage strategies. In this retrospective study, we sought to determine the characteristics and outcomes for patients with FCH at our transplant center.
  
  
  METHODS
  All cases of HCV-positive OLT recipients from July 2007 through July 2010 were reviewed. Patient demographics, donor characteristics, and the post-OLT clinical course were analyzed. Tacrolimus-based immunosuppression was used. FCH was treated by conversion to cyclosporine A (CsA) and aggressive treatment with pegylated interferon (IFN) alpha2A and ribavirin (RBV). Liver biopsies and HCV RNA were obtained frequently per protocol or for cause.
  
  
  RESULTS
  The rate of FCH during the study period was 13.5% (5/37). Of the 5 patients with FCH (4 males, 4 Caucasian), mean age was 51 (± 4.8) years and the Model for End-Stage Liver Disease (MELD) score at listing was 26.6 (± 10). Three of the 5 received liver and kidney (L/K) transplants (60%); the rate of L/K transplant in non-FCH patients was 12.5%. HCV RNA levels ranged from 5 to 6.69 log IU/mL pre-OLT; none were on anti-HCV therapy at the time of OLT. Mean ischemic time was 385 (± 152) minutes; donor age was 34.4 (± 13.7) years. No CMV infections developed postoperatively. Time to histologic HCV recurrence was 2 (± 2.23) months (range, 1-6); FCH occurred at 2.2 (± 2.2) months. Patients were converted from tacrolimus to CsA and treated with IFN and RBV; 2 were changed to consensus IFN. HCV RNA increased post-OLT in all, but responded to therapy in 4 of 5. None of the L/K recipients experienced renal graft rejection during treatment. Four of 5 had clinical and histologic improvement; 1 progressed to cirrhosis with minimal inflammation. One-year patient survival after OLT in this group was 80%. Liver allograft rejection occurred in 60% at 4.7 (± 5.5) months and was treated by CsA and prednisone dosage adjustments. In this cohort of patients undergoing OLT for HCV, FCH occurred early after OLT but responded to aggressive management with conversion from tacrolimus to CsA and treatment with pegylated IFN or consensus IFN/RBV. There was a higher rate of combined L/K transplants in the FCH group compared with the non-FCH group. Liver allograft rejection occurred in 60% of cases, but responded to treatment in all; no renal graft rejection occurred in the 3 with L/K transplants while on IFN. One-year graft and patient survival was 80%.
  
  
  CONCLUSIONS
  Better survival with FCH is possible with early initiation of IFN/RBV therapy with close monitoring of biopsies and viral load, and conversion from tacrolimus to CsA. Treatment can be performed even in L/K transplantation recipients, although it is associated with a higher incidence of treatable liver allograft rejection.
authors.affiliation: Yale University School of Medicine, Department of Surgery, New Haven, CT, USA.
authors.forename: B
authors.initials: B
authors.lastname: Cimsit
authors.forename: D
authors.initials: D
authors.lastname: Assis
authors.forename: C
authors.initials: C
authors.lastname: Caldwell
authors.forename: A
authors.initials: A
authors.lastname: Arvelakis
authors.forename: T
authors.initials: T
authors.lastname: Taddei
authors.forename: S
authors.initials: S
authors.lastname: Kulkarni
authors.forename: M
authors.initials: M
authors.lastname: Schilsky
authors.forename: S
authors.initials: S
authors.lastname: Emre
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D002780:Cholestasis, Intrahepatic / Q000209:etiology / Q000601:surgery*; D015331:Cohort Studies; D016572:Cyclosporine / Q000008:administration & dosage; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D006526:Hepatitis C / Q000150:complications* / Q000188:drug therapy / Q000821:virology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D016559:Tacrolimus / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D016572:Cyclosporine; C100416:peginterferon alfa-2a; D016559:Tacrolimus