Five-year survival of patients transplanted for HCC is excellent, with a steady improvement in survival over the past decade. It is possible that the published criteria for patient selection may have contributed to the better outcome.

Recent studies have shown that dopamine receptor agonists induce expression of Fos-like immunoreactivity in rat striatal neurons. The protooncogene c-fos belongs to a family of immediate early genes that are rapidly induced in fibroblasts by growth factors. In light of previous findings that several immediate early gene mRNAs that encode proven or putative transcription factors are differentially regulated by neuronal stimulation in vivo, we have examined the effect of dopaminergic agents on mRNA levels of several such genes using in situ hybridization and northern blot analysis. d-Amphetamine (2.5-10 mg/kg i.p.) causes a rapid but transient dose-dependent increase in zif268 and jun-B mRNA levels in striatum that was abolished by striatal 6-hydroxydopamine lesions or by pretreatment with the specific D1 receptor antagonist SCH-23390 but not by specific D2 receptor antagonists. Apomorphine, a dopamine agonist that acts at both D1 and D2 receptors, and SKF-38393, a specific D1 receptor agonist, produce similar mRNA changes in rats pretreated with either 6-hydroxydopamine or reserpine, whereas LY-171,555, a specific D2 receptor agonist, has no effect. Direct dopamine agonist effects on these immediate early gene mRNA levels are also blocked by D1 but not by D2 antagonists. We observed similar, although less robust, changes in c-fos and fos-B mRNA levels. These results demonstrate that striatal D1 dopamine receptors are coupled to activation of multiple transcription factor genes, including zif268 and jun-B as well as members of the fos family.

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The objective of this study was to characterize the prevalence of asymptomatic liver transminase (LT) abnormalities in a healthy, low-risk adult population and identify associated risk factors. We reviewed 2340 completed medical records of participants in our Executive Health Program, which provided screening medical evaluations for executives. LT (alanine aminotransferase and aspartate aminotransferase) were considered abnormal if they above normal range for our laboratory. Subjects were excluded if they had a history of viral hepatitis, nonviral liver disease, or an identifiable cause of LT elevation. Of the 2340 subjects 2294 met inclusion criteria and all had AST recorded, but only 1309 had ALT recorded. In all, 341 subjects (14.9%) were found to have abnormal LT and in those who had less than 3 drinks per day, 13.9% had elevated LT and 3.6% had LT twice the upper limit of normal. Of the 1309 subjects in whom both AST and ALT were measured, 20.8% had abnormal LT and 6.3% had LT twice the upper limit of normal. On univariate analysis age < 60 (P = 0.005), male sex (P < 0.0001), body mass index > or = 30 (P < 0.0001), cholesterol > or = 200 mg/dl (P = 0.018), and triglycerides > or = 200 mg/dl (P < 0.0001) were associated with abnormal LT; all these variables except cholesterol were significant by logistic regression analysis. The odds ratio of abnormal LT and LT 2 times normal was 1.79 (CI 1.20-2.68) and 2.50 (CI 1.04-6), respectively, in subjects with one risk factor, and 2.80 (CI 1.07-7.34) and 4.73 (CI 0.91-24.5), respectively, in subjects with four risk factors. In conclusion, there is a high prevalence of LT abnormalities in this healthy population. Subjects with multiple risk factors should be considered for screening.

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In patients with cirrhosis, anemia is common and is likely to be multifactorial, including decreased erythrocyte production, sequestration due to hypersplenism, hemolysis, and increased blood loss from gastrointestinal bleeding. Renal dysfunction is also common in liver disease and this may also cause anemia. However, an association between anemia and renal dysfunction has not been reported in patients with cirrhosis. Our objective was to determine whether anemia in cirrhotic patients is independently related to renal dysfunction. We conducted a retrospective chart review of patients in our institution listed for liver transplantation. We collected simultaneous data on age, hemoglobin, creatinine, albumin, liver enzymes, prothrombin time, and bilirubin. We excluded patients who were hospitalized or deceased to avoid confounding variables. Two hundred eighty-six (female n = 130) patients with a mean age of 52.8 +/- 9.7 (range, 18-73) years were studied. Renal dysfunction (creatinine > 1.2 mg/dL) was present in 55 (19%) patients, and anemia (hemoglobin < 12 g/dL) was seen in 115 (40%) patients. Anemia was more common in patients with renal dysfunction (64 versus 34%; P < 0.001) compared to those with normal renal function. Creatinine, prothrombin time, and bilirubin showed an inverse relationship (all P's < 0.001) with hemoglobin, and albumin showed a positive correlation with hemoglobin (P < 0.001). Multivariate analysis showed that creatinine (OR, 2.4; 95% CI, 1.05-5.3; P = 0.038), prothrombin time (P = 0.026), bilirubin (P = 0.035), and albumin (P = 0.001) were independent predictors of anemia. Renal dysfunction is an important cause of anemia in patients with cirrhosis. The role of erythropoietin in the management of anemia in patients with cirrhosis and renal dysfunction should be explored in prospective studies.

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