Autoantibody prevalence in chronic hepatitis B virus infection: Effect in interferon alfa

G V Gregorio, H Jones, K Choudhuri, A Vegnente, F Bortolotti, G Mieli‐Vergani, D Vergani – 1 September 1996 – The most effective treatment of chronic hepatitis B virus (HBV) infection is interferon alfa (IFN‐α), a potentially severe side effect of which is the induction of autoimmunity. To assess whether IFN‐ α causes clinical or serological autoimmune manifestations, we studied 61 children randomized to receive 5 MU/m2 of IFN‐α three times per week for 12 weeks, with or without steroid priming or no treatment.

Heparan sulfate proteoglycan expression in chronic cholestatic human liver diseases

T Roskams, J Rosenbaum, R De Vos, G David, V Desmet – 1 September 1996 – The mechanism of bile ductular reaction and accompanying fibrogenesis depends on interactions of ductular cells with the matrix and growth factors. Heparan sulfate proteoglycans (HSPGs) are essential cofactors in cell‐matrix adhesion processes, in cell‐cell recognition systems, and in receptor‐growth factor interactions.

The role of gallbladder emptying in gallstone formation during diet‐induced rapid weight loss

R L Gebhard, W F Prigge, H J Ansel, L Schlasner, S R Ketover, D Sande, K Holtmeier, F J Peterson – 1 September 1996 – Obese persons are at risk for cholesterol gallstones because their bile is saturated with cholesterol. The risk increases during rapid weight loss by means of certain very‐low‐calorie diets or gastric bypass surgery. Gallstone risk factors during rapid weight loss include increased bile cholesterol saturation index and gallbladder stasis.

Immunogenicity of biliary epithelium: Investigation of antigen presentation to CD4+ T cells

M P Leon, M F Bassendine, J L Wilson, S Ali, M Thick, J A Kirby – 1 September 1996 – The intrahepatic biliary epithelium is susceptible to extensive T‐cell‐ mediated damage during primary biliary cirrhosis, primary sclerosing cholangitis, and hepatic allograft rejection. During these processes, human intrahepatic biliary epithelial cells (HIBEC) become activated and express high levels of the lymphocyte adhesion molecules, intercellular adhesion molecule‐1 (ICAM‐1) and lymphocyte‐associated antigen (LFA)‐3, and of class II MHC antigens.

Increased expression of proliferating cell nuclear antigen in liver allograft rejection

Mukunda B. Ray, Timothy Schroeder, Scott E. Michaels, Douglas W. Hanto – 1 September 1996 – Detection of proliferating cell nuclear antigen is useful for the study of proliferative activity of neoplastic and non‐neoplastic lymphoid, parenchymal, and mesenchymal cells. Allograft rejection is associated with the recruitment of circulating cells and their proliferation in the graft.

Gene therapy: Advances and limitations

Nancy L. Ascher – 1 September 1996 – Recombinant adenovirus vectors are efficient at transferring genes into somatic tissues but are limited for use in clinical gene therapy by immunologic factors that result in the rapid loss of gene expression and inhibit secondary gene transfer. This study demonstrates that systemic coadministration of recombinant adenovirus with soluble CTLA4lg, which is known to block co‐stimulatory signals between T cells and antigen presenting cells, leads to persistent adenovirus gene expression in mice without long‐term immunosuppression.

Hepatitis B virus envelope variation after transplantation with and without hepatitis B immune globulin prophylaxis

W F Carman, C Trautwein, J van Deursen, K Colman, E Dornan, G McIntyre, J Waters, V Kliem, R Müller, H C Thomas, M P Manns – 1 September 1996 – Hepatitis B virus (HBV) replicates via an intermediate RNA step. High frequency of polymerase errors with additional selection pressure leads to mutations in the HBV genome.

Development of monoclonal gammopathy precedes the development of Epstein‐Barr virus‐induced posttransplant lymphoproliferative disorder

Andrew D. Badley, Daniel F. Portela, Robin Patel, Robert A. Kyle, Thomas M. Habermann, John G. Strickler, Duane M. Ilstrup, Russell H. Wiesner, Piet De Groen, Randall C. Walker, Carlos V. Paya – 1 September 1996 – Epstein‐Barr virus (EBV)‐induced posttransplant lymphoproliferative disorder (PTLD) develops in 3% to 10% of solid organ transplant recipients with a resultant mortality of up to 70%. Unfortunately, there is no current marker which identifies patients who will develop this disease.

Mutation in HBV RNA‐dependent DNA polymerase confers resistance to lamivudine in vivo

G A Tipples, M M Ma, K P Fischer, V G Bain, N M Kneteman, D L Tyrrell – 1 September 1996 – The (‐) enantiomer of 3′‐thiacytidine (lamivudine) has been found to be a potent inhibitor of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) replication. Mutation of methionine to valine or isoleucine at the YMDD (tyrosine, methionine, aspartate, aspartate) motif of the HIV reverse transcriptase has been shown to be responsible for lamivudine resistance in HIV. The hepadnaviruses also have the YMDD motif in their DNA polymerase.

Destruction of Kupffer cells increases survival and reduces graft injury after transplantation of fatty livers from ethanol‐treated rats

Zhi Zhong, Henry Connor, Ronald P. Mason, Wei Qu, Robert F. Stachlewitz, Wenshi Gao, John J. Lemasters, Ronald G. Thurman – 1 September 1996 – This study investigated the role of Kupffer cells on survival and graft injury in transplanted fatty livers from rats treated acutely with ethanol. Donor rats were given ethanol (5 g/kg, by mouth) 20 hours before explantation, and liver grafts were preserved in University of Wisconsin cold storage solution for 24 to 42 hours prior to implantation. Blood samples were taken from the inferior vena cava for 3 hours after implantation.

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