engleski

Short-term metabolic alterations following liver transplantation

INTRODUCTION: Liver cirrhosis is associated with multiple metabolic disturbances affecting carbohydrate, lipid and protein metabolism. Depletion of glycogen deposits necessitates active gluconeogenesis, using glycerol and alanine as substrates, thus contributing to enhanced lipolysis and muscle protein catabolism ; loss of liver parenchyma contributes to the development of an insulin resistant state via reduced insulin clearance. Aberrant accumulation of adipose tissue hormones is also documented, possibly contributing to insulin resistance (IR). Liver transplantation provides amelioration of the aforementioned disturbances, however with the onset of immunosuppressant related complications- development of metabolic syndrome or its components. OBJECTIVES: The aims of this research were: - to explore the dynamics of metabolic parameter changes, including adiponectin (ADN) and leptin (LPN), in the early post-transplant period - to determine the factors associated with insulin resistance prior and post liver transplantation METHODS: The study had a prospective design and included consecutive adult patients undergoing liver transplantation in a single centre. Patients with overt diabetes prior to transplantation were excluded. Protocol: Patients were evaluated for demographical, clinical and laboratory variables at three set time points- prior to transplantation, 3- and 6-months postoperatively. IR was assessed by the Homeostasis Model Assessment 2 (HOMA-2) model and ADN and LPN concentrations were determined by validated enzyme-immunoassay methods. Statistical analyses: One-way repeated measures analysis of variance (ANOVA) was conducted to investigate dynamics of metabolic parameters at different time points with follow up comparisons. Multiple linear regression was used to determine the factors associated with IR. RESULTS: A total of 68 patients (66% males) with a mean age of 55, 9 ± 8, 7 years was included in the study. The major causes of liver disease were alcohol in 49% and hepatitis C in 25% of cases. Significant metabolic changes were observed following liver replacement, with an increase of fasting blood glucose (FBG), glycosylated haemoglobin, insulin sensitivity, triglyceride and cholesterol levels, while a decrease of beta cell function, insulin resistance, leptin and adiponectin was noted. Almost no significant metabolic changes were observed between the 3 and 6 month timepoints. Insulin resistance was related to leptin levels in the pre-transplant setting, and to leptin, FBG and calcineurin inhibitor type in the posttransplant setting, and showed no relation to gender, creatinine level, HCV status, adiponectin and body mass index levels. CONCLUSIONS: Liver transplantation elicited a reduction in insulin resistance with probably consequent alleviation of beta-cell function and insulin levels. Levels of adiponectin and leptin also decrease, possibly reflecting re- establishment of adipocytokine homeostasis significantly afflicted by the end stage liver disease. Further follow-up is needed to elucidate the significance of the observed trend towards hyperlipidaemia and hyperglycaemia short-term after liver transplantation on the patient outcomes.

liver cirrhosis, transplantation, metabolic alterations, insulin resistance, adipokines

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