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These results confirm that corticosteroids can be completely avoided from the beginning after liver transplantation. Double drug immunosuppression with tacrolimus and mycophenolate mofetil is effective and safe in terms of patient and graft survival as well as incidence and severity of rejection. In order to avoid under- or over-immunosuppression, which may be caused by impaired absorption or metabolism, close drug monitoring is advised.

Studies reported here show that the recently discovered acute-phase protein, lipopolysaccharide-binding protein (LBP), is synthesized by hepatocytes. For these studies, explanted rabbit hepatocytes were grown in the presence of ³⁵S-methionine. Biosynthetically labelled LBP in the cells and supernatant was identified using immunoprecipitation with rat anti-rabbit LBP antibody. This antibody immunoprecipitates both the LBP polypeptide and the glycosylated protein. With a cell-free translation system a comparison of RNA from normal rabbit liver with that isolated from acute-phase rabbit liver indicated that a translatable LBP message is only found in the RNA from acute-phase liver. Studies with explanted rabbit hepatocytes showed that several forms of LBP distinguishable by migration in SDS-PAGE are secreted into the extracellular medium. This heterogeneity probably is a result of differences in glycosylation of LBP since pretreatment of the hepatocytes with tunicamycin results in accumulation of a single polypeptide with an apparent mass of 50 kD in SDS-PAGE. Explanted rabbit hepatocytes spontaneously synthesize and secrete LBP and express LBP mRNA as detected by cell-free translation; thus, it was not possible to upregulate the expression of LBP. Nevertheless, these studies form the basis for future investigations on the regulation of LBP biosynthesis.

Human T lymphocytes infiltrating the liver in chronic active hepatitis B (CAH-B) and primary biliary cirrhosis were isolated from liver biopsy cores, cloned by limiting dilution technique and expanded in vitro. Phenotypic and functional analysis demonstrates that this tissue infiltrate represents a heterogeneous cell population. However, when compared to peripheral blood lymphocytes of the same patients, a marked enrichment for T8+ cytotoxic T cells was found to exist at a local site in both types of chronic liver disease. These data provide support for the notion that liver cell injury in CAH-B and PBC may be mediated by a common immunologic mechanism likely executed by cells of the T lineage.

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