Nonspecificity of monoclonal antibody Tordji-22 for the detection of hepatitis C virus in liver transplant recipients with cholestatic hepatitis.

Detection of hepatitis C virus (HCV) antigens in liver tissue provides important diagnostic and pathological information. Limited studies have been performed on tissue taken after liver transplantation for HCV. In this study, serial post-liver transplantation biopsy tissue from patients with recurrent HCV was tested, with particular interest in patients showing severe cholestatic hepatitis. HCV-related antigens were detected using the commercial monoclonal antibody, Tordji-22. Initial results were promising, showing intense positive staining, especially in areas of hepatocyte ballooning. HCV-negative donor tissue was consistently negative by staining. However, as a final control for the level of tissue damage, HCV negative posttransplantation biopsy tissue showing hepatocyte ballooning was examined. These tissues also showed positive staining. All attempts to eliminate this nonspecific interaction failed. In conclusion, Tordji-22 was associated with nonspecificity in this posttransplantation population, and care is warranted when using this monoclonal antibody.

Post-transplant quasispecies pattern remains stable over time in patients with recurrent cholestatic hepatitis due to hepatitis C virus.

BACKGROUND/AIMS: Several studies have shown that cholestatic recurrent hepatitis is associated with very high HCV RNA loads in liver transplant recipients. The aim of this study was to investigate whether a correlation exists between cholestatic hepatitis post-transplant and the population of viral quasispecies. METHODS: One hundred and nine serial sera samples were tested from 15 recurrent HCV patients. Four of these patients showed severe cholestatic recurrent hepatitis, 11 patients demonstrated non-cholestatic recurrent hepatitis post-transplant. Quasispecies were detected by RT-PCR amplification of the HVR1 followed by single-stranded conformational polymorphism analysis. RESULTS: Forty-one samples from four cholestatic patients were tested. All four patients showed very stable quasispecies patterns post-transplant. One cholestatic patient also showed a stable quasispecies band pattern following retransplantation, again associated with severe cholestatic hepatitis. Sixty-eight samples were tested from the 11 non-cholestatic patients. In contrast, these patients showed significantly more quasispecies bands than the cholestatic patients. The noncholestatic patients also displayed fluctuating band patterns post-transplant. Serial samples were tested after retransplantation in one non-cholestatic patient, with a fluctuating pattern again seen. There was a negative correlation between the HCV RNA load in serum and the number of quasispecies bands. CONCLUSIONS: Stable hepatitis C viral quasispecies associated with persistently high viral load in post-transplant cholestatic hepatitis suggest that viral escape from immune pressures may play a role in the pathogenesis of this condition.

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

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.

Spontaneous clearance of hepatitis C virus infection post-liver transplantation is associated with rapidly changing quasispecies: a single case report.

Hepatitis C virus (HCV) clearance post-liver transplantation is uncommon. This is a case report of a patient who, after liver transplantation, developed cholestatic hepatitis characterized by severe graft dysfunction, in conjunction with high viral load. This was, however, followed by viral clearance and normalization of allograft function. The clinical features of this case and the quasispecies patterns during the illness and the clearance periods are described. In addition, management implications in terms of immunosuppressive therapy are discussed.