Fibrosing cholestatic hepatitis in renal transplant recipients with hepatitis C virus infection

Abstract

Fibrosing cholestatic hepatitis (FCH) has been described as a specific manifestation of hepatitis B virus (HBV) infection in liver allograft recipients characterized by a rapid progression to liver failure. Only sporadic cases have been reported in other immunocompromised groups infected with HBV and in a few transplant recipients with hepatitis C virus (HCV) infection. We present the occurrence of FCH in 4 HCV-infected renal transplant recipients within a series of 73 renal transplant recipients with HCV infection followed up closely serologically and with consecutive liver biopsies. All 4 patients received the triple-immunosuppressive regimen (azathioprine, cyclosporine A, methylprednisolone). The interval from transplantation to the appearance of liver dysfunction was 1 to 4 months and to histological diagnosis, 3 to 11 months. The biochemical profile was analogous to a progressive cholestatic syndrome in 3 patients, whereas the fourth patient had only slightly increased alanine aminotransferase and ␥-glutamyl transferase (␥GT) levels. Liver histological examination showed the characteristic pattern of FCH in 2 patients, whereas the other 2 patients had changes compatible with an early stage. All patients were anti-HCV negative at the time of transplantation, whereas 2 patients, 1 with incomplete and 1with complete histological FCH features, seroconverted after 3 and 31 months, respectively. The patients were HCV RNA positive at the time of the first liver biopsy and showed high serum HCV RNA levels (14 to 58 ؋ 10 6 Eq/mL, branched DNA). HCV genotype was 1b in 3 patients and 3a in 1 patient. After histological diagnosis, immunosuppression was drastically reduced. Two patients died of sepsis and liver failure 16 and 18 months posttransplantation, whereas the seroconverted patients showed marked improvement of their liver disease, which was histologically verified in 1 patient. In conclusion, FCH can occur in HCV-infected renal transplant recipients. It seems to develop as a complication of a recent HCV infection during the period of maximal immunosuppression and is associated with high HCV viremia levels. There are indications that drastic reduction of immunosuppression may have a beneficial effect on the outcome of the disease.

Morphological and biochemical characterization of a human liver in a uPA-SCID mouse chimera

“…High viremia of this magnitude can be observed, however, when HCVinfected patients are undergoing immune suppressive therapy after transplantation. [22][23][24] Histological analysis of the liver of an HCV-infected mouse showed that most human hepatocytes were infected. Despite careful electron microscopic analysis, no viral or subviral particles could be identified in human hepatocytes.…”

Erratum to: Cholestatic Hepatitis C in Immunocompromised Settings

“…This high level of HCV RNA indicates markedly enhanced replication of HCV, leading to direct cellular degeneration and death [13]. HCV genotype 1b was reported to have a more frequent and severe form of recurrent HCV compared with other genotypes, but these results are conflicting [4,10,18].…”

Treatment of Hepatitis C Virus Infection in Kidney Transplant Recipients: Case Report

“…9,10 Among our patients, only the first case was known to be HCV positive; other two patients did not show anti-HCV antibodies. Unfortunately, the search for RNA HCV was not performed on these patients before transplantation, so it is impossible to determine whether they were in a window period or whether it was an old infection.…”

“…7 Initially described in 1991 as a complication of a hepatitis B infection (HBV) in liver transplant recipient, 8 this rare entity appears to be associated with HCV infection in renal transplantation. 9 It seems to be associated with rapid viral replication in the immediate period following transplantation with the development of rapidly progressive hepatic failure with ensuing death. Herein we have presented three cases of renal transplant patients who developed FCH and underwent treatment for HCV infection.…”