Cholestatic Hepatitis (Ch) in Liver Allografts of Hepatitis C (Hcv) Patients: Histopathologic Progression and Correlation With HCV-Rna Viral Levels

38 PURPOSE: A subset of HCV liver transplant patients develop a severe form of CH. In this study we characterize the histopathologic features on serial biopsies and investigated the role of HCV viral replication in disease progression. MATERIALS and METHODS: Seven cases of CH were identified among patients transplanted for HCV endstage liver disease. CH was defined as hyperbilirubinemia > 5mgs/dl for a duration of > 1 month. No other causes of cholestasis were identified. All biopsies [median #9 (6-12)] were reviewed as well as native explant and allograft explant livers. The tissues were evaluated for multiple histologic features and overall tissue diagnosis. HCV viral load was measured in 28 native explant, 6 allograft explant liver tissues and 2 allograft biopsies with CH using AMPLICOR HCV MONITOR™ test. RESULTS: 5/7 cases of CH required retransplantation. Two died < 1 month following retransplantation of infections. All three surviving retransplant patients had recurrent CH, of these, two cases developed bridging fibrosis 3 and 20 months following retransplantation. The histopathologic progression of CH in the original allografts was similar in all 7 cases. Mild lobular hepatitis is present initially and precedes the development of ballooning degeneration and cholestasis. Ballooning degeneration dominated the histologic picture during the cholestatic phase and culminated in centrizonal collapse. There was no evidence of chronic rejection in any of the biopsies or allografts. The native explant liver tissue of CH cases had significantly higher HCV levels than an unselected group of 21 HCV native explant livers (P<.013). Four cases had levels >25,000 copies/ug DNA, while all non-cholestatic cases had lower levels. Two cases of CH with <10,000 copies/ug DNA in the native explant did not require retransplantation. HCV levels in 3 allograft explants were >20,000 copies/ug DNA. The 2 cases with the highest levels showed the most ballooning. The levels in the 2 biopsies with CH were >50,000 copies/ug DNA, and were higher than in native explant or allograft explant livers. CONCLUSIONS: 1) CH is an aggressive disease with poor prognosis and recurs after retransplantation. 2) The histopathological progression is predictable. 3) HCV RNA levels >25,000/ug DNA in native explant liver tissue is associated with CH in allografts requiring retransplantation.