1/7. Immunohistochemical assessment of hepatitis c virus antigen in cholestatic hepatitis after liver transplantation.BACKGROUND: patients with common variable immunodeficiency may exhibit rapidly progressive hepatitis when infected with hepatitis c virus (HCV), leading to cirrhosis and liver failure. liver transplantation in these patients may result in a cholestatic form of HCV reinfection with exceptionally high virus loads. AIMS: To report an immunohistochemical investigation of the pretransplant and post-transplant liver of one such patient. methods/RESULTS: On immunohistochemical staining of frozen sections with anti-HCV core monoclonal antibody or fluorescein labelled human polyclonal anti-HCV IgG, no HCV antigens were demonstrated in the native cirrhotic liver removed at transplant, despite a viral load of 10(6.4) genomes/g. The transplanted liver, collected six weeks post-transplant, exhibited cholestatic recurrent hepatitis, had an HCV virus load of 10(10) genomes/g of liver, and revealed HCV antigen in the cytoplasm of most hepatocytes, with a pronounced periportal distribution. No virus antigen was demonstrable in other cell types. The core antigen was also detected in paraffin wax embedded, formaldehyde fixed tissue of this liver after high temperature antigen retrieval, but not in the native cirrhotic liver or a selection of HCV positive livers collected pretransplant from immunocompetent patients. Attempts to delineate the distribution of E1, NS3, and NS4 antigens were unsuccessful because monoclonal antibodies to these antigens produced "false positive" staining of foci of hepatocytes in the post-transplant livers of HCV seronegative patients with cholestasis. CONCLUSION: This case provided an opportunity to study the natural development of HCV during acute infection in the absence of an immune response, and may help to elucidate the pathogenesis of HCV recurrence in liver allografts.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
2/7. A case of carbimazole-induced intrahepatic cholestasis. An immune-mediated reaction?A patient is described with cholestatic hepatitis following the use of carbimazole. A liver biopsy specimen showed intracanalicular cholestasis and some mononuclear cell infiltrate in the portal triades, consistent with drug toxicity; indications of an autoimmune or viral pathogenesis were absent. Rechallenge with the drug precipitated jaundice and disturbed liver function once more. carbimazole induced a blastogenic response of patient lymphocytes in vitro. Both may suggest the involvement of an immune-mediated reaction, especially as it has been shown that sensitized lymphocytes may produce a cholestatic factor on stimulation with antigen.- - - - - - - - - - ranking = 0.090909090909091keywords = antigen (Clic here for more details about this article) |
3/7. Fibrosing cholestatic hepatitis in a transplant recipient with hepatitis b virus precore mutant.A patient with hepatitis b virus (HBV) precore mutant (seropositive for hepatitis B surface antigen [HBsAg], anti-hepatitis B e antigen [HBeAg], and HBV dna) who underwent orthotopic liver transplantation for end-stage liver disease is described. Sequencing of the HBV precore region of the pretransplant serum sample confirmed the presence of the precore stop-codon mutant (G-->A mutation in codon 1896) only. The patient received HBV immunoglobulin prophylaxis for 6 months but HBV recurred thereafter with a mild hepatitic flare, and he remained seropositive for HBsAg, anti-HBe, and HBV dna. The initial hepatitic illness resolved in 3 months. The patient remained well for another 16 months before presenting with fibrosing cholestatic hepatitis (FCH). During his entire initial hepatitic flare, quiescent period, and final FCH phase, he remained seropositive for HBsAg, anti-HBe, and HBV dna. Moreover, sequencing of the serum HBV dna in final FCH phase showed the presence of the identical HBV precore mutant. Immunohistochemical staining showed extensive expression of HBsAg/pre-S1, pre-S2, and hepatitis B core antigen, but HBeAg was scarcely detectable. This case illustrates that (1) recurrence of HBV precore mutant infection can occur in liver; (2) it can give rise to FCH; and (3) hepatic accumulation of HBeAg is not essential for the development of FCH.- - - - - - - - - - ranking = 0.27272727272727keywords = antigen (Clic here for more details about this article) |
4/7. Fibrosing cholestatic hepatitis in renal transplant recipients.Fibrosing cholestatic hepatitis in a specific histologic manifestation of hepatitis b virus infection consisting of periportal fibrosis, hepatocyte ballooning, cholestasis, a relatively scant inflammatory infiltrate, and marked overexpression of hepatitis B viral antigens in hepatocytes. Until recently, fibrosing cholestatic hepatitis had been reported only in recipients of liver allografts. In this report, we present two patient in whom this lesion developed following renal transplantation. Both patients had previous liver biopsies showing relatively mild histologic changes. In one patient, the lesion developed early after retransplantation, during the period of maximal immunosuppression. However, in the second patient this lesion developed after withdrawal of immunosuppression. In both cases, death occurred within a few months because of progressive liver disease. Since this lesion can develop in "relatively healthy" hepatitis B carriers following transplantation of organs other than liver, these patients should have careful monitoring of their liver disease. Moreover, since the disease may progress despite withdrawal of immunosuppression, these patients would clearly benefit from the development of more effective therapies for posttransplant hepatitis B.- - - - - - - - - - ranking = 0.090909090909091keywords = antigen (Clic here for more details about this article) |
5/7. Prolonged survival in fibrosing cholestatic hepatitis with long-term ganciclovir therapy.A 45-yr-old man underwent liver transplantation for cirrhosis due to hepatitis B and developed recurrent infection. Serial liver biopsies revealed fibrosing cholestatic hepatitis, an entity that is associated with rapid graft failure, and this was treated with long-term intravenous ganciclovir therapy. The patient is alive and well 2 yr after transplantation, despite the presence of well-established cirrhosis and a marked accumulation of intrahepatic hepatitis B surface and core antigens. It is postulated that partial reduction of viral replication resulted in an incomplete syndrome in which rapid graft failure did not occur, but progressive fibrosis developed. Our case suggests that newer nucleoside analogues that provide a greater degree of inhibition to hepatitis b virus replication may greatly improve the outcome of patients with recurrent infection after liver transplantation.- - - - - - - - - - ranking = 0.090909090909091keywords = antigen (Clic here for more details about this article) |
6/7. Fulminant hepatic failure in a renal transplant recipient with positive hepatitis b surface antigens: a case report of fibrosing cholestatic hepatitis.This 28-year-old male, a hepatitis b virus (HBV) carrier, received cadaveric renal transplantation and was maintained on cyclosporin A and prednisolone. jaundice occurred 8 months after the transplantation and he died 2 weeks later due to hepatic failure. The liver histologic findings were compatible with fibrosing cholestatic hepatitis (FCH), which is caused by HBV and has only been reported in liver allografts of orthotopic liver transplantations. This is the first case of FCH developing in a renal transplant recipient. The report illustrates that (1) FCH is also a unique histologic entity in renal transplantations; (2) FCH might occur in a liver chronically infected by HBV without co-existing hepatitis d virus; and (3) FCH can cause fulminant hepatic failure within one year after transplantation while the patient is still in an immunosuppressed state.- - - - - - - - - - ranking = 0.36363636363636keywords = antigen (Clic here for more details about this article) |
7/7. Cholestatic hepatocellular injury with azathioprine: a case report and review of the mechanisms of hepatotoxicity.azathioprine is a drug commonly used for the treatment of inflammatory bowel disease, organ transplantation and various autoimmune diseases. Hepatotoxicity is a rare, but important complication of this drug. The cases reported to date can be grouped into three syndromes: hypersensitivity; idiosyncratic cholestatic reaction; and presumed endothelial cell injury with resultant raised portal pressures, venoocclusive disease or peliosis hepatis. The components of azathioprine, 6-mercaptopurine and the imidazole group, may play different roles in the pathogenesis of hepatotoxicity. The strong association with male sex, and perhaps with human leukocyte antigen type, suggests a genetic predisposition of unknown type. Many of the symptoms of hepatotoxicity, such as nausea, abdominal pain and diarrhea, can be nonspecific and can be confused with a flare-up of inflammatory bowel disease. As well, the subtype resulting in portal hypertension can occur without biochemical abnormalities. A 63-year-old man with Crohn's disease who is presented developed the rare idiosyncratic form of azathioprine hepatotoxicity, but also had a severe disabling steroid myopathy, peripheral neuropathy, resultant deep venous thrombosis and pulmonary embolism related to immobility, and a nosocomial pneumonia. His jaundice and liver enzyme levels improved markedly on withdrawal of the drug, returning to almost normal in five weeks. Treating inflammatory bowel disease effectively while trying to limit iatrogenic disease is a continuous struggle. Understanding the risks of treatment is the first important step. There must be a low threshold for obtaining liver function tests, especially in men, and alertness to the need to discontinue the drug or perform a liver biopsy should patients on azathioprine develop liver biochemical abnormalities, unexplained hepatomegaly or signs of portal hypertension.- - - - - - - - - - ranking = 0.090909090909091keywords = antigen (Clic here for more details about this article) |