Search

Background: The prevalence of diabetes is high after transplantation. We hypothesized that liver transplantation induces additional alterations of glucose homeostasis because of liver denervation., Methods: Nondiabetic patients with a heart (n=9) or liver (n=9) transplant and healthy subjects (n=8) were assessed using a two-step hyperglycemic clamp (7.5 and 10 mmol/L). Thereafter, an oral glucose load (0.65 g/kg fat free mass) was administered while glucose was clamped at 10 mmol/L. Glucose appearance from the gut was calculated as the difference between glucose appearance (6,6 2H2 glucose) and exogenous glucose infusion. Plasma insulin, glucagon-like peptide (GLP)-1 and gastric inhibitory polypeptide(GIP) concentrations were compared after intravenous and oral glucose., Results: After oral glucose, the glucose appearance from the gut was increased 52% and 81% in liver- and heart-transplant recipients (P<0.05). First-pass splanchnic glucose uptake was reduced by 39% in liver-transplant and 64% in heart-transplant patients (P<0.05). After oral but not intravenous glucose, there was an impairment of insulin secretion in both transplant groups relative to the controls. Plasma concentrations of GIP and GLP-1 increased similarly in all three groups after oral glucose., Conclusions: First-pass hepatic glucose extraction is decreased after heart and liver transplant. Insulin secretion elicited by oral, but not intravenous glucose, is significantly reduced in both groups of patients. There was no difference between liver- and heart-transplant recipients, indicating that hepatic denervation was not involved. These data suggest an impairment in the beta-cell response to neural factors or incretin hormones secondary to immunosuppressive treatment.

Background: The liver can synthesize fatty acids from carbohydrate (de novo lipogenesis [DNL]). We hypothesized that stimulation of this process may be involved in the development of obesity and dyslipidemia, 2 conditions frequently encountered after liver transplantation., Methods: Hepatic fractional DNL and glucose metabolism were measured in 2 groups of 5 patients (age 36.8 +/- [SD] 14.9 years, BMI 26.3+/-5.3 kg/M2) 1 to 5 years after liver transplantation and 8 healthy subjects (age 28.1+/-5.3 years, BMI 27.2+/-4.5 kg/M2). Subjects were studied while receiving an isoenergetic nutrition (based on 1.1 x their basal energy expenditure) as hourly oral liquid formula during 10 hours. Their hepatic DNL was measured by infusing 1-13C acetate and measuring tracer incorporation in VLDL-palmitate. Their glucose metabolism was assessed by means of 6,6-2H2 glucose and indirect calorimetry., Results: Two liver transplant recipients and 4 healthy subjects were obese, as defined by a BMI > 27 kg/M2. Fractional hepatic DNL was not different in the 2 groups of subjects: liver transplant recipients 3.1+/-1.7% vs 3.2+/-2.1% in healthy subjects. In both groups, DNL increased in proportion to BMI. When both groups were analyzed together, BMI was positively correlated with DNL (DNL = 0.28 x BMI - 4.28, r2 = .445, p < .05). Whole body glucose turnover was 15.0+/-4.4 micromol/kg per minute in liver transplant recipients and 15.8+/-4.1 micromol/kg per minute in healthy subjects (NS). Net carbohydrate oxidation tended to be lower in liver transplant recipients (8.1+/-2.6 micromol/kg per minute) than in healthy subjects (10.4+/-2.4 micromol/kg per minute; NS). Net nonoxidative glucose disposal (4.0+/-2.7 in liver transplant recipients vs 1.9+/-1.8 in healthy subjects, NS) and energy expenditure (0.065+/-0.01 vs 0.065+/-0.01 kJ/kg per minute) were similar in both groups., Conclusions: These results indicate that fractional hepatic DNL is not altered by liver transplantation during near continuous nutrition. The disposal of orally administered carbohydrate is also essentially unchanged. This strongly argues against a role of hepatic DNL in the pathogenesis of obesity and dyslipidemia after liver transplantation.

From 1988 to June 2000 138 transplantations were performed in 129 adult patients. Actuarial patient and graft survivals have been 80.7% and 75.4% at one year and 67.8% and 63.5% at 10 years. This compares favourably with the statistics of the European Liver Transplant Registry that collected data from more than 30,000 grafts. Over the twelve years of activity, the indications have become more liberal and the techniques have been simplified. The waiting list has therefore grown and some patients are now unfortunately dying before a graft can be found because the number of brain dead donors remains stable. In order to palliate this shortage, older donors are now being accepted even with co-morbidities and/or moderate alterations of the liver function tests. The use of live donors and the split of the best cadaveric grafts for two recipients will also reduce the gap between the demand and the offer.

Hypothesis: Liver transplantation results in hepatic denervation. This may produce alterations of liver energy and substrate metabolism, which may contribute to weight gain after liver transplantation., Design: Prospective clinical study., Setting: Liver transplantation clinics in a university hospital., Patients: Seven nondiabetic patients with cirrhosis were recruited while on a waiting list for liver transplantation. Seven healthy subjects were recruited as controls., Intervention: Orthotopic liver transplantation., Main Outcome Measures: Evaluation of energy and substrate metabolism after ingestion of a glucose load with indirect calorimetry was performed before, 2 to 6 weeks after, and 5 to 19 months after transplantation. Whole-body glucose oxidation and storage and glucose-induced thermogenesis were calculated., Results: Patients with cirrhosis had modestly elevated resting energy expenditure and normal glucose-induced thermogenesis and postprandial glucose oxidation and storage. These measures remained unchanged after liver transplantation despite a significant increase in postprandial glycemia. Patients, however, gained an average of 3 kg of body weight after 5 to 19 months compared with their weight before transplantation., Conclusion: Liver denervation secondary to transplantation does not lead to alterations of energy metabolism after ingestion of a glucose load.

Background: In type I glycogenosis, mutation of the glucose-6-phosphatase gene results in absent glucose-6-phosphatase activity in liver cells leading to fasting hypoglycemia. Liver transplantation is expected to normalize glucose homeostasis., Methods: Endogenous glucose production (6,6 2H2 glucose) was measured after an overnight fast and during exogenous 13C-labeled glycerol infusion in a patient with glycogenosis type I 24 months after liver transplantation and in a group of healthy subjects., Results: Compared with healthy subjects, the glycogenosis patient had normal fasting glucose production and glucose and insulin concentrations after liver transplantation, but mildly elevated plasma glucagon concentrations. Gluconeogenesis from exogenous glycerol (13C glucose synthesis) was similar and did not lead to enhancement of glucose production in both healthy controls and the patient., Conclusions: Liver glucoregulatory function is restored by orthotopic liver transplantation in type I glycogenosis.

Background: The liver plays a central role in glucose homeostasis by releasing glucose in the fasting state and by taking up and converting into glycogen part of the glucose absorbed from the gastrointestinal tract after meal ingestion., Methods: To determine whether the hepatic denervation that accompanies liver transplantation interferes with these functions, we assessed glucose tolerance to an oral glucose load in seven patients at 2-6 weeks after orthotopic liver transplantation, in six patients after kidney transplantation, and in six healthy controls. Hepatic glycogen synthesis was non-invasively assessed over the 4 hours after ingestion of a glucose load by monitoring hepatic uridine diphosphoglucose turnover with 13C galactose and acetaminophen., Results: Liver and kidney transplant recipients had increased postprandial glucose concentrations but normal hepatic uridine diphosphoglucose turnover, indicating an unaltered hepatic glycogen synthesis., Conclusions: These results indicate that denervated liver transplants have an adequate glucoregulatory function. Postprandial hyperglycemia in liver transplant recipients is therefore not due to alterations of liver glucose metabolism.

Impaired glucose tolerance or diabetes mellitus are frequent complications after organ transplantation, and are usually attributed to glucocorticoid and immunosuppressive treatments. Liver transplantation results in total hepatic denervation which may also affect glucoregulation. We therefore evaluated postprandial glucose metabolism in a group of patients with liver cirrhosis before and after orthotopic liver transplantation. Seven patients with liver cirrhosis of various etiologies, 6 patients having received a kidney transplant, and 6 healthy subjects were studied. Their glucose metabolism was evaluated in the basal state and over 4 hours after ingestion of a glucose load with 6.6 (2) H glucose dilution analysis. The patients with liver cirrhosis were studied before, and again 4 weeks (range 2-6) and 38 weeks (range 20-76, n=6) after orthotopic liver transplantation. Basal glucose metabolism was similar in liver and kidney transplant recipients. Impaired glucose tolerance was present in both groups, but postprandial hyperglycemia was exaggerated and lasted longer in liver transplant patients. Postprandial insulinemia was lower in liver transplant recipients, while C-peptide concentrations were comparable to those of kidney transplant recipients, indicating increased insulin clearance. Glucose turnover was not altered in both groups of patients during the initial 3 hours after glucose ingestion, but was higher in liver transplant early after transplantation during the fourth hour. Postprandial hyperglycemia remained unchanged in liver transplant recipients 38 weeks after liver transplantation, despite substantial reduction of immunosuppressive and glucocorticoid doses. We conclude that liver transplant recipients have severe postprandial hyperglycemia which can be attributed to insulinopenia (secondary, at least in part, to increased insulin clearance) and a late increased glucose turnover. These changes may be secondary to hepatic denervation.

This paper presents the results of the first 7 orthotopic liver transplants performed in Lausanne between December 1988 and September 1990. 6 patients are surviving; their rehabilitation is excellent.