Article

Sustained resolution of fibrosing cholestatic hepatitis C despite viremic relapse after stopping pegylated interferon and ribavirin therapy.

Liver Transplantation (Impact Factor: 3.94). 03/2007; 13(2):309-11; author reply 312. DOI: 10.1002/lt.21019
Source: PubMed
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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.
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    ABSTRACT: With the improvements in post-transplant immunosuppression, the incidence of acute cellular rejection and chronic rejection has decreased significantly over the last few years. This has led to alterations in the presentation of rejection with more patients suffering from late acute rejection, which commonly has different histological appearances compared with the early post-transplant period. There is now a shift in interest to the long-term outcome of liver allografts, with recurrent disease being the most common cause of abnormal histology. The combination of long-term immunosuppression and recurrent disease leads to complex and atypical features on biopsy specimens. Other causes of liver graft inflammation include de novo autoimmune disease and 'idiopathic' post-transplant hepatitis. There is gathering evidence that idiopathic hepatitis can have significant consequences in terms of tissue fibrosis and progression to cirrhosis. Future developments in genetic and immune profiling may lead to liver biopsy becoming a predictive tool to identify patients in which immunosuppression can be safely withdrawn.
    Expert Review of Clinical Immunology 09/2012; 8(7):645-61. · 2.89 Impact Factor
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    ABSTRACT: Chronic hepatitis C (CHC)–related cirrhosis is the leading indication for liver transplantation (LT). However, the recurrence of a hepatitis C virus (HCV) infection after transplantation is universal and is associated with worse outcomes. Fibrosing cholestatic hepatitis (FCH) is a particularly severe manifestation of a recurrent HCV infection and frequently results in graft failure and death. The identification of risk factors for FCH is important but has been limited by the low frequency of FCH. The interleukin-28B (IL-28B) genotype is important in an HCV infection: it is related to the clinical severity of an acute infection and may play a role in the development of FCH as well. Two hundred seventy-two consecutive LT cases for CHC were studied at a single institution. Consensus criteria were used to define an FCH cohort. The remainder of the study population served as a control group. The IL-28B genotype (at the rs12979860 locus) from both the donor and the recipient was determined, and other clinically relevant data were tabulated. A nonparametric statistical analysis was performed. Twelve cases of FCH were identified, and they were compared to a control group of 260 LT cases without FCH. A detailed analysis of clinical characteristics, including treatment responses and outcomes, was tabulated. FCH was associated with the earlier recurrence of HCV infections, higher HCV viral loads, and lower levels of immunosuppressive medications. There was a nonsignificant increase in recipient IL-28B non-CC genotypes in cases developing FCH. In conclusion, a high HCV viral load and earlier recurrence were identified as risk factors for FCH. It is still unclear what role immunosuppression plays in the pathogenesis of FCH and whether IL-28B polymorphisms constitute a risk factor. Collaborative studies with larger numbers of study subjects are needed in order to define these issues. Liver Transpl 19:1311-1317, 2013. © 2013 AASLD.
    Liver Transplantation 12/2013; 19(12). · 3.94 Impact Factor