Cholestatic hepatitis C following liver transplantation: an outcome-based histological definition, clinical predictors, and prognosis.

Cholestatic hepatitis C virus (HCV) is a rare form of recurrent HCV following liver transplantation (LT) without specific diagnostic criteria. An outcome-based method to improve its diagnosis and a description of its prognosis are needed. All 1-year post-LT protocol liver biopsy samples and biopsy samples initially reported to show cholestatic HCV from patients transplanted with HCV between February 2002 and December 2009 were reviewed for the inflammation grade, the fibrosis stage, and 4 cholestatic HCV features: ductular proliferation, canalicular cholestasis with or without intracellular cholestasis, hepatocyte swelling with or without lobular disarray, and sinusoidal/pericellular fibrosis. We used patient and graft survival to define histological criteria for cholestatic HCV, and compared the clinical features of these patients to those of patients with minimal or significant post-LT fibrosis. One hundred seventy-nine patients were analyzed, the median age was 56 years, and 73% were male. Patients with 3 or more of the 4 cholestatic HCV criteria had significantly worse survival (log-rank P < 0.001) regardless of the fibrosis stage, and this was used as our novel definition of cholestatic HCV. Using this definition, we found that 27 patients (15%) had cholestatic HCV, 53 (30%) had significant fibrosis (stage ≥ 2/4), and 99 (55%) had minimal fibrosis (stage < 2/4). The final model for clinical predictors of cholestatic HCV included donor age [odds ratio (OR) = 1.37 per decade, P = 0.04] and previous rejection (Banff grade ≥ 5; OR = 4.19, P = 0.002). Total bilirubin was the strongest laboratory predictor of cholestatic HCV (area under the curve = 0.93), whereas the HCV viral load was not a significant predictor. The final model of post-LT survival included the pathology group {cholestatic HCV [hazard ratio (HR) = 6.07, P < 0.001] and significant fibrosis (HR = 2.53, P = 0.02)}, donor age (HR = 1.49 per decade, P < 0.001), and cold ischemia time (HR = 1.11 per hour, P = 0.02). In conclusion, we propose diagnostic criteria for cholestatic HCV that include specific criteria (the presence of at least 3 of the 4 histopathological features on biopsy) and other supportive and exclusionary criteria. Older donor age and rejection increase the risk of cholestatic HCV, and an elevation in the total bilirubin level may help to identify these patients. These criteria must be validated prospectively.