High levels of hepatitis C virus RNA in native livers correlate with the development of cholestatic hepatitis in liver allografts and a poor outcome

Abstract

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.)

Controversies in the management of hepatitis C virus infection after liver transplantation

“…Patients with rapidly progressive cholestatic hepatitis seem to have very high levels of HCV RNA, more than 10-fold greater than the average patient with recurrent HCV, fewer quasispecies, and reduced lymphocyte recognition of HCV antigens. [9][10][11][42][43][44][45][46][47] These observations support a scenario in which the immune response to HCV is reduced, and in which the virus can proliferate rapidly without mutations. It is therefore important to note that most cases of rapidly progressive cholestatic hepatitis C seem to develop after treatment of presumed acute rejection with either monoclonal antibodies or high-dose bolus corticosteroids.…”

“…[9][10][11]42,43 The syndrome is observed in less than 5% of patients who undergo liver transplantation for chronic HCV infection, typically presents within 1 to 3 months of transplantation, and progresses to graft failure within 3 to 6 months. The pathogenesis of this syndrome remains undefined.…”

Impact of immunosuppression on immunopathogenesis of liver damage in hepatitis C virus-infected recipients following liver transplantation

“…1). [9][10][11][12][13] This usually begins to develop within 1 month of transplantation and may progress during a 3-to 6-month period in a fashion similar to fibrosing cholestatic hepatitis B virus infection. Histological characteristics of cholestatic HCV vary from severe centrizonal hepatocyte cholestasis with centrizonal hepatocyte ballooning and little lobular or portal inflammation to an injury that can mimic large-duct obstruction with cholangiolar proliferation.…”

“…Histological characteristics of cholestatic HCV vary from severe centrizonal hepatocyte cholestasis with centrizonal hepatocyte ballooning and little lobular or portal inflammation to an injury that can mimic large-duct obstruction with cholangiolar proliferation. [9][10][11][12][13]15 This syndrome presumably reflects an alternative response to HCV reinfection, rather than the more common early acute hepatitis, because it tends to occur at approximately the same time posttransplantation.…”

Erratum to: Cholestatic Hepatitis C in Immunocompromised Settings

“…The theory of quasispecies patterns remains controversial. Some studies suggest immunosuppression enhances divergence of the HCV quasispecies and results in the emergence of new variants [19][20][21][22]. Other studies show that after transplantation, the quasispecies pattern remains stable over time in patients with recurrent cholestatic hepatitis HCV, which suggests that viral escape from immune pressure may play a pathogenic role [23].…”