Hepatitis C virus-related fibrosing cholestatic hepatitis after cardiac transplantation: is azathioprine a contributory factor?
ABSTRACT We report a patient who acquired hepatitis C virus (HCV) infection at cardiac transplantation, developing fibrosing cholestatic hepatitis (FCH) with early liver failure and a fatal outcome. FCH is a recently described clinicopathological entity characterized by a cholestatic pattern of serum liver enzyme abnormalities, a progressive course leading to liver failure, and a pathological picture defined by periportal fibrosis, neutrophilic infiltrates and signs of histological cholestasis. Although it was initially described secondary to hepatitis B virus infection, it has also been recently related to HCV infection. Some histopathological features consistent with azathioprine hepatotoxicity like cholestasis, perisinusoidal fibrosis, veno-subocclusive lesions and nodular regenerative hyperplasia were also observed in this case. Therefore, a direct cytopathic effect of HCV and the concurrent pathogenic role of azathioprine hepatotoxicity may be involved in the development of this complication of transplantation.
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ABSTRACT: The estimated prevalence of hepatitis C virus (HCV) infection among lung transplant (LT) recipients is 1.9%. Many thoracic transplant programs are reluctant to transplant HCV-seropositive patients due to concerns of hepatic dysfunction caused by immunosuppression. The aims of this study are to survey current practices of US LT programs regarding HCV-seropositive patients and using the Organ Procurement and Transplantation Network/United Network for Organ Sharing database and to assess the clinical outcomes of HCV-positive compared with HCV-negative LT recipients. A survey of US transplant centers that have performed more than 100 LTs was conducted. In addition, 170 HCV-seropositive and 9259 HCV-seronegative recipients who received HCV-seronegative donor organs between January 1, 2000, to December 31, 2007, were identified from the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Outcome variables including patient survival were compared between the two groups. A total of 64.4% centers responded to the survey. Ten of 29 (34.5%) programs would not consider HCV-seropositive patients for LT. Among the 19 programs that will consider HCV-seropositive patients, only five centers would transplant actively viremic patients. Overall patient survival rates of HCV-seropositive patients were similar to HCV-seronegative patients (84.7% at 1 year, 63.9% at 3 years, 49.4% at 5 years for HCV-seropositive group vs. 82.0% at 1 year, 65.0% at 3 years, 51.4% at 5 years for HCV-seronegative group, P=0.712). Relative risk of recipients for death remained statistically insignificant after adjusting for recipient age, donor age, obesity, sensitization, serum creatinine, and medical condition at time of transplant (relative risk [RR]=1.07 [0.84-1.38], P=0.581). Since 2000, patient survival rates of HCV-positive patients are identical to those who are HCV-negative. However, most of these HCV-seropositive patients were probably nonviremic.Transplantation 06/2011; 91(11):1293-6. · 3.78 Impact Factor
- American Journal of Transplantation 03/2013; 13(s4):147-168. · 6.19 Impact Factor
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ABSTRACT: 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. © 2012 American Association for the Study of Liver Diseases.Liver Transplantation 10/2012; · 3.94 Impact Factor