Center for Liver Disease and Transplantation, Division of Digestive and Liver Diseases, Columbia University College of Physicians and Surgeons, New York, New York.
Background: Cholestatic hepatitis C is a rare form of recurrent hepatitis C (HCV) infection after liver transplantation (LT) without specific diagnostic criteria. An outcome-based method to improve diagnosis and description of prognosis are needed. Methods: All 1-year post-LT protocol liver biopsies and those initially reported as cholestatic HCV for HCV patients transplanted between 2/02-12/09 were reviewed for inflammation grade, fibrosis stage, and 4 described cholestatic HCV features: ductular proliferation, canalicular ± intracellular cholestasis, hepatocyte swelling ± lobular disarray, and sinusoidal/pericellular fibrosis. We utilized patient and graft survival in order to define histologic criteria for cholestatic HCV, and compared clinical features in these patients to those with minimal or significant post-LT fibrosis. Results: ¬179 patients were analyzed, median age 56, 73% male. Patients with ò 3/4 cholestatic HCV criteria had significantly worse survival (logrank p<0.001) regardless of fibrosis stage, and this was used as our novel cholestatic HCV criteria. Using this definition, 27 (15%) patients had cholestatic HCV, 53 (30%) significant fibrosis (ò stage 2/4) and 99 (55%) minimal fibrosis (< stage 2). The final model for clinical predictors of cholestatic HCV included donor age (OR 1.37 per decade, p=0.04) and previous Banff ò 5 rejection (OR 4.19, p=0.002). Total bilirubin was the strongest laboratory predictor of cholestatic HCV (AUC 0.93) while HCV viral load was not a significant predictor. The final model of post-LT survival included pathology group [cholestatic HCV (HR 6.07, p<0.001), significant fibrosis (2.53, p=0.02)], donor age (1.49 per decade, p<0.001) and cold ischemia time (1.11 per hour, p=0.02). Conclusions: We propose diagnostic criteria for cholestatic HCV, which include specific criteria (the presence of ò 3 of 4 histopathologic lesions on biopsy) and other supportive and exclusionary criteria. Older donor age and rejection increase the risk of cholestatic HCV, and elevation in TB may help identify these patients.