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The cytosolic β-glucosidase of mammalian liver has been implicated in the metabolic transformation of plant glycosides, such as vicine and amygdalin, which are associated with the development of toxic syndromes. We investigated which cell types express cytosolic β-glucosidase in guinea pig liver, and characterized the contribution of this enzyme to the hydrolysis of aromatic glucosides in cultured cells and in tissue slices. Cytosolic β-glucosidase was expressed in hepatocytes and not in Kupffer or endothelial cells as determined by enzyme-specific activity and Western blots of liver cell extracts. Intracellular β-glucosidase activity was visualized using the fluorescent β-glucosidase substrate, resorufin β-d-glucoside, and shown to be caused by the cytosolic β-glucosidase using the inhibitors, conduritol β-epoxide and dinitrophenol-2-deoxy-2-fluoro-β-d-glucopyranoside (DNP2FGlc). Staining of fresh liver slices with resorufin β-glucoside revealed that cytosolic β-glucosidase is expressed in all hepatocytes, with no significant portal-central gradient. These data indicate that cytosolic β-glucosidase is a hepatocyte-specific enzyme, and support the hypothesis that cytosolic β-glucosidase in the liver functions to hydrolyze small glucosides absorbed by the intestine. Furthermore, toxic injury to cultured hepatocytes by CCl4 resulted in release of cytosolic β-glucosidase in parallel with the hepatocyte marker enzymes alanine transaminase and lactate dehydrogenase. This suggests that acute increases in serum levels of cytosolic β-glucosidase in animal models of liver injury may reflect direct injury of hepatocytes.

One thousand one hundred and twenty-eight candidates for liver transplantation were stratified into five urgency-of-need categories by the United Network for Organ Sharing (UNOS) criteria. Most patients of low-risk UNOS 1 status remained alive after 1 yr without transplantation; the mortality while waiting was 3% after a median of 229.5 days. In contrast, only 3% of those entered at the highest risk UNOS 5 category survived without transplantation; 28% died while waiting, the deaths occurring at a median of 5.5 days. The UNOS categories in between showed the expected gradations, in which at each higher level fewer patients remained as candidates throughout the 1-yr duration of study while progressively more died at earlier and earlier times while waiting for an organ. In a separate study of posttransplantation survival during the same time period, the best postoperative results were in the lowest-risk UNOS 1 and 2 patients (88% combined), and the worst results were those in UNOS 5 (71%). However, a relative risk cross-analysis showed that a negative benefit of transplantation may have been the result in terms of 1-yr survival for the low-risk elective patients, but that a gain in life extension was achieved in the potentially lethal UNOS categories 3, 4 and 5 (greatest for UNOS 3). These findings and conclusions are discussed in terms of total care of patients with liver disease, and in the context of organ allocation policies of the United States and Europe. Many of the earlier presentations at this Consensus Development Conference have focused on specific diseases and the wisdom of performing liver replacement for disorders that are apt to recur (such as cancer, hepatitis and alcoholic cirrhosis). Others have discussed limiting the operation to prime-of-life candidates, with exclusion of the very young or aged. Expansion of the donor pool has been proposed in the “splitting” of livers that are shared between two candidates or in the use of liver fragments from living donors. These subjects have been judiciously addressed in the context of organ shortage and allocation, leaving the all-important questions of patient disease severity and complexity almost untouched. To focus on this problem, Bronsther et al. (1) have analyzed elsewhere and we present here in more detail the dynamics in a collection of more than a thousand adult patients who were given candidacy in our program. The results may be useful in policy determination about organ allocation and in definition of the role of liver transplantation in the total armamentarium available to treat hepatic diseases.