Martina Wichlas

PHYSICAL PERFORMANCE AND HEALTH-RELATED QUALITY OF LIFE IN MEN ON A LIVER TRANSPLANTATION WAITING LIST

Twenty-six men on a liver transplant waiting list (12 had alcoholic cirrhosis, 8 suffered from posthepatitic cirrhosis, and 6 from cirrhosis of other etiologies) were eligible for this observation. Nineteen subjects underwent exercise testing to determine oxygen uptake at anaerobic threshold. In all patients dynamometry was performed to determine isokinetic muscle strength of knee extensor muscles, and handgrip. Quality of life was evaluated in all patients with the MOS SF-36 questionnaire. Child-Pugh A patients showed 54 +/- 8%, Child-Pugh B patients 36 +/- 2%, and Child-Pugh C patients 31 +/- 4% of VO2 max predicted at the anaerobic threshold (Kruskal-Wallis ANOVA, p < 0.05). Isokinetic muscle strength of the quadriceps femoris (left/right) was 149 +/- 20/134 +/- 14 Nm in Child-Pugh A, 108 +/- 16/114 +/- 19 Nm in Child-Pugh B, and 89 +/- 10/81 +/- 11 Nm in Child-Pugh C patients (Kruskal-Wallis ANOVA, p < 0.05). MOS-SF36 revealed a Child-Pugh class dependent reduced functional status (Kruskal-Wallis ANOVA, p < 0.05). No significant differences in target parameters were found when analysed according to the etiology of cirrhosis. Patients on the liver transplant waiting list do have a stage dependent reduction in physical health. These data are the basis for longitudinal studies measuring the effects of preoperative rehabilitation programs in these patients.

Thrombopoietic cytokines and reversal of thrombocytopenia after liver transplantation.

OBJECTIVES Thrombopoietin (TPO), the key regulator of platelet production, is mainly produced by the liver and reduced expression of TPO could cause thrombocytopenia in liver cirrhosis. Reversal of thrombocytopenia by orthotopic liver transplantation seems to be mediated through an increase in TPO plasma levels after transplantation, but other cytokines with thrombopoietic activity could augment the actions of TPO on post transplant platelet recovery. DESIGN Measurement of thrombopoietic cytokines before and for 14 days post liver transplantation in a cohort of thrombocytopenic liver transplant patients. METHODS TPO, interleukin-3 (IL-3), IL-6, and IL-11 plasma levels as well as peripheral platelet count were analysed in thrombocytopenic patients with liver disease undergoing orthotopic liver transplantation (17 patients) and followed for 14 days after the intervention. RESULTS Before liver transplantation, TPO plasma levels were undetectable and IL-3, IL-6, and IL-11 levels were normal. Sixteen out of 17 patients showed a significant rise of TPO levels within 2 days after transplantation, with a peak between days 4 and 6, while IL-3 and IL-6 levels did not show a significant rise. IL-11 levels remained normal. Platelet counts were significantly higher than pretransplantation levels by day 14 post transplantation. CONCLUSION Restitution of normal TPO production by liver replacement seems to be of key importance for reversal of thrombocytopenia in liver disease. The early acting thrombopoietic factor IL-3 and the late acting factors IL-6 and IL-11 do not play a major role for recovery of peripheral platelet count after orthotopic liver transplantation.

Thalidomide in advanced hepatocellular carcinoma as antiangiogenic treatment approach: a phase I/II trial.

Background The high vascularity of hepatocellular carcinoma (HCC) seems to be a potential therapeutic target. We evaluated the efficacy, toxicity, and histologic response to thalidomide in advanced HCC in a single center phase I/II pilot trial. Methods Between September 2000 and August 2004 patients with HCC uneligible for any established therapy were enrolled in the study. The initial thalidomide dosage of 100 mg/day was escalated in 100 mg steps weekly up to 300 mg/day based on tolerability. Discontinuation and dose reduction were based on toxicity. Tumor biopsies were scheduled to assess tumor microvessel density and serum levels of angiogenic factors, vascular endothelial growth factor, basic fibroblast growth factor, and endostatin were determined. Results Twenty-eight patients with histologically proven HCC were entered into this study. The median maximum-tolerated dose of thalidomide was 300 mg/day. Most common toxicities were fatigue (75%), dizziness (64%), nausea (43%), and constipation (39%). Two patients had stable disease for 2.6 and 5.4 months, the remaining 26 patients had disease progression. The median overall survival was 5.1 months. Well preserved liver function was associated with longer overall survival on univariate analysis (P=0.0279). The serum concentrations of vascular endothelial growth factor and endostatin increased significantly (P=0.039 and P=0.024, respectively) after 3 months of thalidomide treatment. No clear differences were observed between the serum basic fibroblast growth factor concentrations at study entry and after 3 months (P=0.983). Microvessel density did not decrease significantly during thalidomide therapy (P=0.109). Conclusion Thalidomide is moderately tolerated and minimally effective in large HCC.

Preoperative TNM-classification is a better prognostic indicator for recurrence nof hepatocellular carcinoma after liver transplantation than albumin mRNA in peripheral blood

Abstract Background/Aims: Survival after orthotopic liver transplantation for hepatocellular carcinoma is limited by a high rate of tumor recurrence. A polymerase chain reaction assay based on the detection of albumin mRNA expression in peripheral blood for detection of hematogenous micrometastasis of hepatocellular carcinoma has been described, which may help to select candidates for orthotopic liver transplantation. Methods: The prognostic value of a highly sensitive nested reverse transcription-polymerase chain reaction assay was evaluated in comparison with the TNM-classification of the Internal Union against Cancer in a population of liver transplant candidates. Results: Eighty patients with liver disease and 42 control patients were evaluated. Six of 21 patients with hepatocellular carcinoma and 11 of 59 patients with other diseases of the liver were positive for albumin reverse transcription-polymerase chain reaction, making this assay an indicator of ongoing liver damage without absolute specificity for hepatocellular carcinoma. Twelve patients with hepatoma were followed after liver transplantation and seven of those patients had a tumor recurrence within 12 months. Six of these patients with recurrence had International Union against Cancer stage IV A tumors preoperatively, while only one of them was positive for albumin reverse transcription-polymerase chain reaction before transplantation. Only one patient with a stage I to III tumor had a recurrence within 12 months. Conclusions: Detection of albumin mRNA in peripheral blood by reverse transcription-polymerase chain reaction seems to be an unreliable marker for assessing hematogenous spread of hepatocellular carcinoma. With International Union against Cancer stage IV A being a much better predictor of tumor recurrence, the practical value of albumin mRNA reverse transcription-polymerase chain reaction for patient selection in liver transplant candidates seems to be very limited.