A subset of hepatitis C virus (HCV)-positive liver transplant recipients develop cholestatic hepatitis (CH).We investigated the role of pretransplantation disease activity (estimated by Knodell score and HCV RNA quantitation) in the native liver explant on the development of CH and graft and patient outcome. Eight patients with CH were identified among HCV-positive liver transplants and were compared with 20 consecutive patients with recurrent HCV hepatitis of noncholestatic type in liver transplants. We evaluated all 28 explanted native livers histologically using the Knodell scoring system. HCV viral load was measured in the native explant and 5 allograft explants from the CH group using Amplicor HCV RNA Monitor test. Six of 8 patients with CH had HCV RNA levels of 5,000 copies/ g of DNA or greater in the native liver explant, whereas only 1 of the control group had viral loads greater than this level. Greater HCV RNA levels correlated with worse graft and patient survival (P < .001). The 3-year survival rate in the CH group was 18% compared with 77% in the control group (P < .001). There was no difference in the primary immunosuppressive regimens used in the 2 groups. We conclude that (1) CH has a uniformly poor prognosis, (2) type of immunosuppressive therapy appears to have little influence on the development of CH, (3) high pretransplantation HCV RNA levels in the native explant may predict the development of CH, and (4) patients with high HCV RNA levels in the explanted native liver may be appropriate candidates for antiviral therapy to prevent the development of CH. (Liver Transpl 2001;7:118-124.)
Persistence of hepatitis C virus (HCV) after orthotopic liver transplantation is almost universal in HCV-infected patients. Histological examination of liver biopsy specimens can be variable in distinguishing between recurrent hepatitis C and acute cellular rejection. The purpose of this study is to determine whether hepatic HCV RNA levels can be used to distinguish rejection from recurrent HCV by determining whether hepatic HCV RNA levels correlate with histological characteristics and clinical course. Seventy-two biopsy specimens were evaluated from 36 liver transplant recipients with HCV and elevated liver-related enzyme levels. Based on histological findings and clinical response to therapy, patients were defined as belonging to 1 of 5 groups: (1) definite rejection, (2) probable rejection, (3) indeterminate findings, (4) probable HCV, and (5) definite HCV. Hepatic HCV RNA was quantified using the Amplicor Monitor assay (Roche Diagnostic Systems Inc, Branchburg, NJ). There was a difference across groups in HCV RNA levels (P ؍ .046). The median HCV RNA level was 10,695 copies/mg of tissue DNA in the definite-HCV group compared with 1,024 copies/mg of tissue DNA in the definite-rejection group. Using pairwise comparisons, significant differences were found between definite HCV and definite rejection, probable HCV and definite rejection, probable HCV and probable rejection, and probable HCV and indeterminate. Our findings support the following conclusions. C irrhosis secondary to hepatitis C virus (HCV) infection is the most common indication for orthotopic liver transplantation (OLT) in the United States and the world. HCV persists in almost all individuals after OLT, and recurrence of HCV hepatitis is a significant cause of morbidity and graft loss. Distinguishing recurrent HCV hepatitis from acute cellular rejection (ACR) in the transplanted liver can be difficult because the histological features of the 2 conditions can overlap. At the same time, the distinction is critical because ACR is treated with an increase in immunosuppressive medication and recurrent HCV hepatitis is treated with a decrease of the same. Serum HCV RNA levels have been shown to correlate with recurrent HCV hepatitis by some investigators, 1-4 but not others. [5][6][7] The current study endeavors to determine whether the use of hepatic HCV RNA levels from liver biopsy specimens after OLT can help distinguish between the 2 entities.In this study, we evaluated liver biopsy specimens and clinical course of 36 patients with hepatitis C who underwent OLT at our institution. Each biopsy specimen was classified based on histological and clinical criteria, including response to medical intervention. Biopsy specimens indicative of either recurrent HCV or ACR were compared with those characteristic of but less definitive for recurrent HCV or ACR and with those in which findings were mild or indeterminate. We examined whether differences in hepatic HCV RNA levels among these groups could help distinguish recurrent HCV and ACR.
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