1/3. Efficacy of lamivudine for the treatment of hepatitis b virus infection after liver transplantation in children.BACKGROUND: There is at present very little information about hepatitis b virus (HBV) infection in children after liver transplantation. This is the first study to assess the safety and efficacy of lamivudine in this patient population. methods: We describe three children aged 5-14 years who underwent liver transplantation for fulminant hepatitis A, hyperoxaluria, and cystic fibrosis. Despite adequate immunoprophylaxis, two of the children who were serum hepatitis B surface antigen-positive before transplantation (HBV dna-negative by hybridization) had a reactivation of the disease, and one had a de novo HBV infection, at 12-18 months after transplantation. lamivudine 3 mg/kg was administered on a compassionate-use basis for 14-36 months. RESULTS: After 1 month of therapy, HBV dna disappeared from the serum in all patients by hybridization and in two patients by polymerase chain reaction. In all three children, alanine transaminase levels normalized. One child developed lamivudine resistance after 22 months with no evidence of hepatic decompensation. Repeated liver histological studies revealed progression of hepatic fibrosis in one child. All children remained serum hepatitis B surface antigen- and hepatitis B e antigen-positive. No adverse effects of the drug were noted. CONCLUSION: lamivudine is beneficial and well tolerated in children with HBV infection after liver transplantation.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/3. Persistence of hepatitis a virus in fulminant hepatitis and after liver transplantation.A peroxidase-labelled, specific mouse monoclonal antibody to hepatitis a virus (HAV) and an in situ hybridization technique (streptavidin-biotin-horseradish peroxidase reaction) with an HAV-specific cDNA probe (recombinant plasmid pAWHA comprising 1.8 kb of the HAV-specific cDNA, located toward the 3' end of the genome) were used to detect HAV in liver tissues in two patients with fulminant viral hepatitis type A treated by liver transplantation after a protracted (day 40: case 1) and relapsing (day 60: case 2) clinical course. HAV antigens and HAV-specific genomic sequences were detected in the hepatectomy tissues and in serial biopsies of the liver grafts through to final follow-up at 2 months (case 2) or death at 7 months after re-grafting for chronic rejection (case 1). In the fulminant liver parenchyma, numerous degenerating and some surviving hepatocytes were positive and randomly scattered. The immunoperoxidase staining was predominantly cytoplasmic and often granular. The localization of the cDNA probe was predominantly nuclear/perinuclear but was occasionally cytoplasmic. High-titre IgM-anti-HAV antibodies persisted until death (case 1) or resolution (5 months) of an acute hepatitis (case 2), which occurred at 2 months, accompanied by HAV antigen (ELISA), in stool. Intact replicating virus particles must have been present in one or more sites in each case, including extrahepatic locations, with a viraemia as the most likely explanation for subsequent reinfection of the grafts.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |
3/3. in situ hybridization studies of hepatitis A viral rna in patients with acute hepatitis A.in situ hybridization with oligonucleotide probes has been used to localise hepatitis a virus rna genomic sequences in formalin-fixed and routinely processed human liver biopsies from three patients. Using radiolabelled Sulphur-35 antisense probes, viral genomic sequences were found in all three cases, but signal intensity was greatest in cases 1 and 2 with fulminant hepatitis, and was minimal in the third case of resolving hepatitis biopsied 2 months after acute illness. Localisation showed the viral rna to be present in hepatocytes, sinusoidal cells and inflammatory cells in and around the portal tracts. Both cases showed signal in similar cell types, but the distribution of staining was predominantly periportal in case 1, whereas lobular staining was more apparent in case 2. Hybridization with sense polarity probes failed to detect any evidence of replicative intermediates of antigenomic viral rna. The presence of hepatitis A rna in phagocytic cells was confirmed using immunohistochemistry for a macrophage marker, CD68, combined with in situ hybridization. In all cases the signal was predominantly cytoplasmic, and this was confirmed with the use of tritiated probes.- - - - - - - - - - ranking = 3keywords = hybridization (Clic here for more details about this article) |