Cholestatic hepatitis after liver transplantation is associated with persistently high serum hepatitis C virus RNA levels

Abstract

Viral recurrence is universal after transplantation for hepatitis C infection. This may lead to difficulties in differentiating allograft dysfunction caused by chronic rejection from hepatitis C virus (HCV) recurrence. Cases of severe cholestatic hepatitis have also been reported in conjunction with reinfection of the graft with HCV. Patients receiving transplants for HCV-related liver disease were studied before and after transplantation by HCV RNA quantitation of serial serum samples. Four major clinical patterns of HCV recurrence could be distinguished posttransplantation: group 1, asymptomatic hepatitis with no significant symptoms; group 2, cholestatic hepatitis with centrilobular ballooning; group 3, hepatitis leading to chronic allograft rejection; and group 4, persistently normal serum aminotransferase levels. Pretransplantation viral load was shown to be an important indicator of disease severity because the group 2 patients had significantly higher pretransplantation viral loads than patients in group 1 (P ‫؍‬ 0.01) and group 4 (P ‫؍‬ 0.005). The group 2 patients also had persistently significantly higher posttransplantation viral loads than the patients in group 1 (P ‫؍‬ 0.01) and group 4 (P ‫؍‬ 0.02), whereas patients who developed chronic allograft rejection showed marked decreases in serum HCV RNA before retransplantation. Patients from group 4 had the lowest viral loads after transplantation. These results show that persisting graft cholestasis due to HCV is associated with persistently high HCV RNA levels compared with other etiologies of graft dysfunction. Prospective studies are needed to determine whether such quantitation may be diagnostically helpful in distinguishing the different patterns of HCV-related graft dysfunction observed after liver transplantation.

Liver biopsy interpretation for causes of late liver allograft dysfunction

“…Features of fibrosing cholestatic hepatitis in- clude centrilobular hepatocyte swelling and degeneration; cholestasis, hepatocyte apoptosis, and portal expansion because of a ductular reaction; fibrosis; and a mild mixed portal inflammation. 66 Fibrosing cholestatic hepatitis is associated with massive HCV replication (e.g., Ͼ40-50 million IU/mL 67,68 ).…”

Hepatitis C virus quasispecies: Misunderstood and mistreated?

“…It is associated with extremely high levels of viral replication, and the high levels of virus with minimal variation probably reflect lack of immune pressure on the HCV in the presence of high levels of immunosuppression. 43,44 It may be analogous to the situation seen in patients infected with HCV who have agammaglobulinemia and display little or no quasispecies development.…”

Recurrencia de la enfermedad hepática primaria después del trasplante hepático

“…Un porcentaje menor de pacientes con recidiva de la hepatitis C, 4-6%, desarrolla una hepatitis colestásica que evoluciona hacia la descompensación hepática dentro de 1 a 6 meses después del injerto 15,20 . Este daño hepático se atribuye a un daño citopático directo del virus sobre el hepatocito 15,20,21 .…”

“…Este daño hepático se atribuye a un daño citopático directo del virus sobre el hepatocito 15,20,21 . La eficacia del tratamiento combinado con interferón pegilado y ribavirina es aún menor que en el resto de los enfermos con recurrencia de hepatitis C. Aunque esta complicación es infrecuente, cuando se evalúan los pacientes que necesitan retrasplante por recurrencia de la hepatitis C, el 19% es debido a una hepatitis colestásica fibrosante de la hepatitis C 22 .…”