Effects of ascites resolution after successful TIPS on nutrition in cirrhotic patients with refractory ascites

OBJECTIVE: Malnutrition is common in patients with decompensated cirrhosis and refractory ascites. The use of transjugular intrahepatic portosystemic stent shunt (TIPS) is effective in eliminating ascites. The purpose of this study was to investigate the effect of TIPS and resolution of refractory ascites on the nutritional status of patients with decompensated cirrhosis. METHODS: Fourteen consecutive patients with refractory ascites and a Pugh score of 9.0+/-0.5 had a TIPS insertion. Biochemical data, resting energy expenditure (REE), total body nitrogen (TBN), body potassium (TBK), body fat (TBF), muscle force (MF), and food intake were recorded before TIPS, and at 3 and 12 months after the procedure. RESULTS: Ten patients completed the study. Baseline values for REE, TBN, TBF, MF, and energy intake were below normal at baseline. There was a significant increase in dry weight, TBN, and REE at 3 and 12 months compared with baseline. TBF improved significantly at 12 months. There was a trend toward an increase in energy intake (p = 0.072). There was no change in protein intake, TBK, MF, and Pugh score. CONCLUSION: In cirrhotic patients with refractory ascites, resolution of the ascites after TIPS placement resulted in improvement of several nutritional parameters, especially for body composition.     

Transjugular intrahepatic portosystemic shunt (TIPS) in patients with refractory ascites: effect on body weight and Child-Pugh score

Objective: This study suggests that patients with medically refractory ascites treated with transjugular intrahepatic portosystemic shunt (TIPS) may have improved in overall clinical status.
Methods: We performed a retrospective study of 35 patients with medically refractory ascites treated with TIPS. Body weight, ascites, and Child-Pugh score were assessed at baseline, at 2 months, and after a mean 8.8-month follow-up interval.
Results: After TIPS, there was significant improvement in Child-Pugh score from 9.7 ± 1.5 to 8.2 ± 2.3. Ascites completely resolved or improved in 23 of 24 patients (96%) who had long term follow-up. Two months after TIPS, there was a significant decrease in weight of 6.1 kg corresponding to a loss of ascites. Between 2 and 8.8 months, there was a significant mean weight gain of 5.5 kg.
Conclusion: This study suggests that patients treated with medically refractory ascites with TIPS may have improvement in overall clinical status, as measured by increase in lean body mass and improvement in Child-Pugh score.     

TIPS implantation raises leptin levels in patients with liver cirrhosis.

Increased leptin levels in patients with liver cirrhosis are postulated to result in malnutrition and increased energy expenditure. Since cirrhotic patients show improved nutritional status after a transjugular intrahepatic portosystemic stent shunt (TIPS), it was the aim of this study to evaluate plasma leptin levels and their influence on nutritional status prior to and after the TIPS procedure. We evaluated plasma leptin levels, body mass index (BMI), Child-Pugh score and pertinent biochemical parameters in 31 patients (19 men and 12 women) with severe complications of liver cirrhosis (74% ethyltoxic men, 50% ethyltoxic in women), prior to and after TIPS. Nineteen cirrhotic patients without TIPS served as controls. In women ascitic-free BMI significantly increased (from 22.8 +/- 4.6 kg/m2 to 23.9 +/- 4.9; p = 0.004 three months after TIPS), whereas in men only a tendency toward higher values (26.1 +/- 4.7 vs. 26.7 +/- 4.4; p = 0.28) was found. Analysis of peripheral venous leptin concentrations before and three months after TIPS revealed a significant increase in women (11.9 +/- 8.8 ng/ml vs. 18.6 +/- 14.9; p = 0.009) and in men (7.7 +/- 6.2 ng/ml vs. 12.2 +/- 9.0; p = 0.005). In addition, the leptin-BMI ratio increase significantly in women and men three months after TIPS implantation (women 0.49 +/- 0.29 vs. 0.73 +/- 0.52; p = 0.017; men 0.28 +/- 0.22 vs. 0.43 +/- 0.28; p = 0.002). On the other hand, patients without TIPS implantation showed no significant alterations of BMI and peripheral venous leptin concentrations. After TIPS implantation in liver cirrhotic patients, leptin levels were increased and the nutritional status improved. Therefore, our analysis suggests that in patients with predominantly ethyltoxic liver cirrhosis, elevated leptin levels are not a major reason for poorer body composition.     

Bioelectrical impedance analysis is a useful bedside technique to assess malnutrition in cirrhotic patients with and without ascites

Protein-calorie malnutrition is associated with poor prognosis in chronic liver disease, but reliable assessment is hampered by changes in body water. We prospectively evaluated the effect of fluid retention on bioelectrical impedance analysis (BIA) as a simple method for the estimation of body cell mass (BCM(BIA)) in 41 patients with cirrhosis (n = 20 with ascites; n = 21 without ascites) using total body potassium counting (BCM(TBP)) as a reference method. Arm muscle area and creatinine-derived lean body mass were compared with total body potassium data. In patients total body potassium was 24.4% lower than in controls and this loss was more severe in patients with ascites (-34.1%; P<.01). BCM(BIA) and BCM(TBP) were closely correlated in controls (r(2) =.87, P<.0001), patients without ascites (r(2) =.94, P <.0001) and patients with ascites (r(2) =.56, P<.0001). Removal of 6.2 +/- 3 L of ascites had only minor effects on BCM(BIA) (deviation of -0.18 kg/L ascites). Limits of agreement between both methods were wider in patients with ascites than in patients without (6.2 vs. 4.2 kg). In patients without ascites arm muscle area (r(2) =.64; P<.001) and lean body mass (r(2) =.55; P<.001) correlated significantly with total body potassium, but not in patients with ascites. For assessment of protein malnutrition in patients with cirrhosis, body cell mass determination by use of BIA offers a considerable advantage over other widely available but less accurate methods like anthropometry or the creatinine approach. Despite some limitations in patients with ascites, BIA is a reliable bedside tool for the determination of body cell mass in cirrhotic patients with and without ascites.     

Loss of total body potassium during rapid weight loss does not depend on the decrease of potassium concentration in muscles. Different methods to evaluate body composition during a low energy diet

OBJECTIVE: The aim of the study was to elucidate whether combustion of skeletal muscle glycogen during a very low calorie diet (VLCD) was associated with decreased muscle potassium content. A comparison between different methods was also performed to evaluate body composition during a VLCD and a low calorie diet (LCD). DESIGN: Dietary treatment of obese women by VLCD and LCD. Measurements after 1 and 2 weeks of VLCD and 6 months of LCD. SUBJECTS: Fifteen perimenopausal obese women aged 46.5+/-1.3 y and 15 of 48.0+/-0.7 y of age. MEASUREMENTS: Skeletal muscle biopsies under local anaesthesia. Body composition measurements by means of deal-energy X-ray absorptiometry (DEXA), and measurements of total body potassium (40K) and total body nitrogen (TBN). Measurements of electrolytes and glycogen concentration in muscle samples. RESULTS: In the first study (1 week of VLCD) skeletal muscle glycogen decreased (P<0.01), but muscle potassium increased (P<0.01). Muscle sodium decreased (P<0.01), while muscle magnesium was unaltered. Body weight decreased by 2.9+/-0.5 kg and 40K decreased. Fat-free mass (FFM) calculated from 40K and DEXA decreased by 2.7 vs 1.9 kg (P<0.001). Body fat measured with DEXA decreased by 1.1 kg (P<0.01), but not body fat calculated from 40K. TBN decreased by 0.03+/-0.01 kg (P<0.05) and FFM calculated from TBN by 2.9+/-0.5 kg (P<0.002). In the second study, 6 months on the LCD resulted in 17.0+/-2.0 kg weight reduction and this was mainly due to reduced body fat, 14. 0+/-2.0 kg measured with DEXA and from 40K (P<0.001). The decrease in FFM was slight. CONCLUSION: One week of VLCD resulted in muscle glycogen depletion but increased muscle potassium content in spite of decreased total body potassium. FFM contributed to the main part of body weight loss during short periods of severe energy restriction, but remained unchanged during long-term dietary treatment. Body fat became mostly responsible for the body weight loss during long-term LCD. Calculations of changes of FFM from 40K and TBN seem to overestimate the FFM decrease associated with short-term VLCD. International Journal of Obesity (2000)24, 101-107     

Modifications of cardiac function in cirrhotic patients treated with transjugular intrahepatic portosystemic shunt (TIPS)

OBJECTIVES: The implantation of a transjugular intrahepatic portosystemic shunt (TIPS) has been shown to exacerbate the hyperdynamic circulation and might induce a significant cardiac overload. We investigated cardiac function before and 1, 3, 6, and 12 months after the TIPS procedure in cirrhotic patients. METHODS: Eleven patients with nonalcoholic cirrhosis were evaluated. Cardiovascular parameters were assessed by two-dimensional Doppler echocardiography. RESULTS: After TIPS, the left ventricular diastolic diameter increased from 26.5 +/- 1.8 mm (basal) to 30.0 +/- 2.8 mm (6 months) (p < 0.05), whereas the ejection fraction showed a slight increase (basal, 64.5 +/- 3.3; 6 months, 68.1 +/- 3.2). The left ventricular pre-ejection period and the isovolumetric relaxation time decreased transiently at 1 month (p < 0.05). An increased velocity in all of the components of pulmonary venous flow (systolic, diastolic, and atrial) documented the accelerated fluxes induced by the procedure. The estimated pulmonary systolic arterial pressure also increased at 1 month (29.5 +/- 1.4 vs 44.1 +/- 1.4 mm Hg, p < 0.05). All of these modifications reverted after 6 months. CONCLUSIONS: Our study demonstrates that nonalcoholic cirrhotic patients, without cardiovascular pathologies, show transient modifications in cardiac dimension and function for 3-6 months after TIPS caused by the increased volume load shunted to the heart.     

Transjugular intrahepatic portosystemic shunt in five children with cystic fibrosis: long-term results

BACKGROUND/AIMS: The aim of this study was to report results of TIPS (transjugular intrahepatic portosystemic shunt) in 5 consecutive children with cystic fibrosis and monitor long-term follow-up results. METHODOLOGY: Five cystic fibrosis patients with multinodular cirrhosis of the liver and complications of portal hypertension (repeated variceal bleeding refractory to endoscopic treatment) underwent TIPS creation. There were 3 males and 2 females aged 8 to 18 years (median 14 yrs), their weight range was 27-51 (median 40) kg. A routine TIPS technique was used. The patients were followed by ultrasonography. RESULTS: The TIPS was successfully performed in all five patients. The mean portosystemic pressure gradient was reduced from 17 to 10 mmHg. There were no deaths related to the procedure. No clinical or laboratory signs of bleeding into the gastrointestinal tract were observed in any patient within the first 30 days following TIPS. There was recurrent bleeding 6 times and asymptomatic stenoses were revealed by ultrasonography 15 times during a follow-up period of 15-81 (median 70) months. All stenoses were successfully dilated. One patient had liver transplantation 15 months after TIPS. Two patients died 6.7 years and 4.5 years following the placement of TIPS due to respiratory insufficiency. CONCLUSIONS: Symptomatic portal hypertension was successfully managed with TIPS in long-term follow-up; multiple reinterventions were required for shunt stenoses. TIPS served as a bridge to liver transplantation in one case.     

Changes in body composition after transjugular intrahepatic portosystemic stent in cirrhosis: a critical review of literature

Change in body composition with reduced muscle mass with or without loss of fat mass occurs in 60–90% of patients with cirrhosis. This has an adverse impact on the outcome of these patients and is an understudied area. Transjugular intrahepatic portosystemic stent (TIPS) is now a standard therapy for portal hypertension but its beneficial impact on nutritional indices is not well recognized. We included all publications on TIPS that had any nutritional index as an outcome measure or end point. Given the heterogeneity of the patient population, differences in study design and outcome measures, a meta‐analysis was not feasible. Data were summarized and interpreted. A total of eight studies have been published on the changes in body composition after TIPS in cirrhosis in a total of 152 patients followed for 3–12 months. Improvement in fat‐free mass and fluid‐free or ascites‐free body weight was reported in all studies. Plasma leptin, IGF1, insulin sensitivity, rate of glucose disposal and growth hormone did not change after TIPS. One study measured muscle strength that improved. Direct measurement of skeletal muscle mass was not performed in any study. TIPS resulted in an improvement in body composition. Given the clinical significance of skeletal muscle and fat mass in cirrhosis, nutritional indices should be considered to be an important outcome measure in patients with TIPS. The mechanism of these is unclear, but its clinical implication is that this may contribute to the improved survival after TIPS.     

Fasting hyperglucagonemia in patients with transjugular intrahepatic portosystemic shunts (TIPS).

BACKGROUND: Hyperglucagonemia has been described to be associated with insulin resistance in patients with liver cirrhosis. Portosystemic shunts may be involved in the etiology of hyperglucagonemia. To test this hypothesis we investigated fasting peripheral plasma glucagon levels before and after portal decompression by transjugular intrahepatic portosystemic shunting (TIPS). METHODS: Glucagon, insulin, plasma glucose, HbA1c, and C-peptide were determined in peripheral venous samples from 21 non-diabetic (ND)- and 15 diabetic patients (D; 3 treated with insulin, 3 with sulfonylurea, 9 with diet alone) with liver cirrhosis, showing comparable clinical features (gender, age, BMI, creatinine, Child-Pugh-score, complications, and etiology of liver cirrhosis) before, 3 and 9 months after elective TIPS implantation. Insulin resistance was calculated as R (HOMA) according to the homeostasis model assessment (HOMA). RESULTS: Glucagon levels before TIPS were elevated in patients with diabetes compared to patients without diabetes (D: 145.4 +/- 52.1 pg/ml vs. ND: 97.3 +/- 49.8 pg/ml; p = 0.057). 3 and 9 months after TIPS implantation glucagon levels increased significantly in ND (188.9 +/- 80.3 pg/ml and 187.2 +/- 87.6 pg/ml) but not in D (169.6 +/- 62.4 pg/ml and 171.9 +/- 58.4 pg/ml). While plasma glucose, HbA1c, and C-peptide were significantly higher in D than in ND, they did not change significantly 3 and 9 months after TIPS implantation. Insulin was increased in D before TIPS (D: 31.6 +/- 15.9 mU/l vs. ND: 14.8 +/- 7.1 mU/l; p = 0.0001). 3 and 9 months after TIPS insulin significantly increased in ND (26.6 +/- 14.7 mU/l and 23.2 +/- 10.9 mU/l vs. 14.8 +/- 7.1 mU/l before TIPS) but not in D. In ND R (HOMA) also increased from 3.5 +/- 2 mU x mmol/l(2) to 5.7 +/- 3.3 mU x mmol/l(2) after 3 and 5.4 +/- 2.6 mU x mmol/l(2) after 9 months. BMI, liver and kidney function did not change with time. CONCLUSION: In non-diabetic cirrhotic patients TIPS implantation is followed by an increase of glucagon. However, this does not result in a worsening of glycemic control, probably because of a simultaneous increase of insulin.     

Loss of body cell mass in Cushing's syndrome: effect of treatment

Cushing's syndrome (CS) is associated with low fat-free mass, but it is unclear whether hypercortisolism causes a loss of whole body protein. Body composition was studied prospectively in 15 patients with untreated CS (n = 14 pituitary adenoma; n = 1 adrenal adenoma), in 15 nonobese healthy controls, and in 15 weight-matched obese controls by 3 different methods: total body potassium counting (TBP), bioelectrical impedance analysis (BIA), and anthropometry. In 6 patients, body composition was studied before and within 6 months after pituitary surgery. In CS patients and weight-matched controls, body weight and total body fat were significantly higher than in nonobese controls. In CS patients, TBP was 18.4% lower than predicted, whereas in weight-matched controls TBP was 7.1% higher than predicted. As compared with nonobese and weight-matched controls, in CS patients TBP indicated a significant loss of body cell mass (BCM) of -20.2 and -21.1%, respectively. A significantly reduced arm muscle area of -21.3% compared with weight-matched controls also indicated a loss of whole body protein. In CS, however, BIA overestimated BCM when compared with TBP by +18% and agreement between BIA and TBP in the individual patient was poor (limits of agreement plus minus 27.6%), indicating the invalidity of standard BIA equations in this population. Measurements performed before and 6 months after successful pituitary surgery demonstrated a significant loss of body weight (-11%) and body fat (-33%), but BCM and muscle mass remained on a constant low level. In conclusion, this study shows that, in patients with CS, a significantly reduced BCM indicates a true protein loss. The second interesting finding is that in the early recovery after successful treatment of hypercortisolism patients lose body fat without gaining BCM or muscle mass.     

Treatment of refractory hepatic hydrothorax with transjugular intrahepatic portosystemic shunt: long-term results in 40 patients

BACKGROUND/AIMS: Hepatic hydrothorax is a complication of portal hypertension secondary to ascites. In this study, we investigated retrospectively the effects of the transjugular intrahepatic portosystemic shunt (TIPS) on hepatic hydrothorax refractory to diuretic treatment. METHODS: Forty patients (Child-Pugh class B, 24 patients; Child-Pugh class C, 16 patients) with hydrothorax refractory to diuretic treatment, pleurocenteses or pleurodesis were included. The TIPS implantation was successful in all patients, who were then followed for 16 +/- 14 months (range 1 day-54 months). RESULTS: TIPS reduced the portosystemic pressure gradient from 26 +/- 6 to 10 +/- 5 mmHg. In the 17 patients whom we followed for 12 months or longer, improvements were found for the Child--Pugh score (8.6 +/- 1.8 v. 6.7 +/- 1.5), serum albumin concentration (3.1 +/- 0.5 v. 3.6 +/- 0.5 g/l), and urinary sodium excretion (22 +/- 29 v. 89 +/- 43 mmol/24 h) (P< 0.05). Two patients developed severe hepatic encephalopathy requiring shunt occlusion. Hydrothorax improved in 82% of patients and resolved in 71% of patients. Fifty per cent of patients developed shunt insufficiency within 7 +/- 9 months, contributing to a probability of relapse-free 1-year survival of 35%. In these patients, shunt revision resulted in a secondary response rate of 82.3%. The 1-year survival was 64%. Both hydrothorax response and survival showed a significant inverse correlation with age over 60 years (P< 0.01 and P< 0.003, respectively) but not with other biomedical variables. CONCLUSION: TIPS is effective for hydrothorax refractory to diuretic treatment and other standard interventions to bridge the time to transplantation. Patients older than 60 years have a poor response and short survival.     

Effects of testosterone administration in human immunodeficiency virus-infected women with low weight: a randomized placebo-controlled study

BACKGROUND: The prevalence of human immunodeficiency virus (HIV) disease is increasing among women, many of whom remain symptomatic with low weight and poor functional status. Although androgen levels may often be reduced in such patients, the safety, tolerability, and efficacy of testosterone administration in this population remains unknown. METHODS: A total of 57 HIV-infected women with free testosterone levels less than the median of the reference range and weight less than 90% of ideal body weight or weight loss greater than 10% were randomly assigned to receive transdermal testosterone (4 mg/patch) twice weekly or placebo for 6 months. Muscle mass was assessed by urinary creatinine excretion. Muscle function was assessed by the Tufts Quantitative Muscle Function Test. Treatment effect at 6 months was determined by analysis of covariance. Results are mean +/- SEM unless otherwise specified. RESULTS: At baseline, subjects were low weight (body mass index [calculated as weight in kilograms divided by the square of height in meters] 20.6 +/- 0.4), with significant weight loss from pre-illness maximum weight (18.7% +/- 1.2%), and demonstrated reduced muscle function (upper and lower extremity muscle strength, 83% and 67%, respectively, of predicted range). Testosterone treatment resulted in significant increases in testosterone levels vs placebo (total testosterone: 37 +/- 5 vs -2 +/- 2 ng/dL [1.3 +/- 0.2 vs -0.1 +/- 0.1 nmol/L] [P<.001]; free testosterone: 3.7 +/- 0.5 vs -0.4 +/- 0.3 pg/mL [12.8 +/- 1.7 vs -1.4 vs 1.0 pmol/L] [P<.001]) and was well tolerated, without adverse effects on immune function, lipid and glucose levels, liver function, or body composition or the adverse effect of hirsutism. Muscle mass tended to increase (1.4 +/- 0.6 vs 0.3 +/- 0.8 kg; P =.08), and shoulder flexion (0.4 +/- 0.3 vs -0.5 +/- 0.3 kg; P =.02), elbow flexion (0.3 +/- 0.4 vs -0.7 +/- 0.4 kg; P =.04), knee extension (0.2 +/- 1.0 vs -1.7 +/- 1.3 kg; P =.02), and knee flexion (0.7 +/- 0.5 vs 0.3 +/- 0.7 kg; P =.04) increased in the testosterone-treated compared with the placebo-treated subjects. CONCLUSIONS: Testosterone administration is well-tolerated and increases muscle strength in low-weight HIV-infected women. Testosterone administration may be a useful adjunctive therapy to maintain muscle function in symptomatic HIV-infected women.     

Transjugular intrahepatic portosystemic shunt (TIPS) for severe veno-occlusive disease of the liver following bone marrow transplantation

Severe veno-occlusive disease (VOD) of the liver is a leading cause of mortality after bone marrow transplantation (BMT). Vascular and parenchymal injuries account for acute portal hypertension and liver failure is frequently present. We describe the results of transjugular intrahepatic portosystemic shunt (TIPS) for the management of VOD after BMT. TIPS was performed in 10 patients with histologically proven severe VOD. Portal hypertension was controlled by TIPS in all patients (mean hepatic venous pressure gradient before, 20 +/- 11 vs 6 +/- 5 mm Hg after TIPS, P < 0.01) without technical complications. Five patients with rapidly worsening VOD died within 10 days of TIPS without any improvement. The five remaining patients with less advanced disease showed improvement in various clinical and biological parameters. Four patients subsequently died. The lone survivor continues to do well with resolution of VOD 6 months after TIPS. TIPS can be performed safely and controls portal hypertension in VOD after BMT. Arguments from the present series and from eight previously reported cases favour earlier application of TIPS to obtain improved overall survival. Bone Marrow Transplantation (2000) 25, 987-992.     

Gastric mucosal responses to intrahepatic portosystemic shunting in patients with cirrhosis

BACKGROUND & AIMS: The response of gastric mucosal lesions in cirrhotic patients with portal hypertension, namely, portal hypertensive gastropathy (PHG) and gastric vascular ectasia (GVE), to transjugular intrahepatic portosystemic shunts (TIPS) is not known. METHODS: Clinical and laboratory evaluation, upper gastrointestinal endoscopy, and Doppler ultrasonography were performed before placement of TIPS and 6 weeks, 3 months, and 6 months after TIPS in 54 patients. Thirty patients had mild PHG, 10 had severe PHG, and 14 had GVE. RESULTS: Approximately 75% of the patients with severe PHG responded to TIPS as shown by improvement in endoscopic findings and by a decrease in transfusion requirements; 89% of patients with mild PHG had endoscopic resolution. Patients with GVE had neither endoscopic resolution nor a decrease in transfusion requirements after TIPS. There was no difference in mortality between the 2 groups. CONCLUSIONS: The results support the position that severe PHG and GVE may be different lesions. Mild and severe PHG respond to TIPS. Because GVE does not respond to TIPS, we recommend that TIPS be avoided for the treatment of gastrointestinal bleeding associated with GVE.     

Effect of insulin treatment on the body composition of Type 2 diabetic patients.

OBJECTIVE: Insulin is used commonly in Type 2 diabetes and is often accompanied by weight gain. The composition of this weight gain is poorly understood. Predominant increases in fat mass could increase cardiovascular risks. The aim of the study was to evaluate insulin-induced body composition changes. RESEARCH DESIGN AND METHODS: Body weight and composition of 35 Type 2 diabetic patients during their first 6 months of insulin therapy was compared with those in 34 Type 2 diabetic individuals treated with insulin for at least 1 year prior to commencing the study. Body composition was determined by the simultaneous measurement of body water spaces and body density. RESULTS: Over 6 months, glycaemic control improved in the new treatment group only (HbA(1c): 7.26 +/- 0.81 vs. 9.66 +/- 1.60%; P < 0.0001), remaining stable in the previously treated group (7.67 +/- 1.25 vs. 7.76 +/- 1.26%; P = NS). Weight significantly increased over time in the newly treated group (+1.7 kg; P = 0.04), but not in the previously treated group (-0.3 kg). It comprised of both fat (+0.85 kg) and fat-free mass (+0.55 kg). Total body water remained unchanged. Using bioelectrical impedance analysis, the gain in fat mass was +2.2 kg; P = 0.048. CONCLUSIONS: Over 6 months, insulin therapy leads to a weight gain of 1.7 kg because of an increase in both fat and fat-free mass. When body composition is determined by bioelectrical impedance analysis, the results are biased by fluctuations in hydration.     

Potential causes of weight gain in type 1 diabetes mellitus

AIM: To investigate the potential causes of weight gain with insulin therapy and improved diabetic control in type 1 diabetes mellitus. METHODS: This was an open-label prospective study of insulin therapy of 6 months duration in an academic medical centre. Twenty-one subjects with type 1 diabetes were enrolled. The goal was to achieve an haemoglobin A1c (HbA1c) in the range of individuals without diabetes (<5.6%). At baseline, 3 and 6 months, weight, resting energy expenditure, appetite assessment, food intake, activity level, HbA1c and 24-h glycosuria and urea nitrogen were measured. Plasma leptin, ghrelin and adiponectin levels and body fat were measured at baseline and 6 months. RESULTS: At baseline, average weight was 73.7 +/- 17.4 kg and HbA1c was 10.0 +/- 2.2%. Weight increased by 2.15 kg (2.69% of baseline) by 6 months whereas the HbA1c dropped by 1.71% (16.3%) to 7.9%. Energy intake differences between 3 and 6 months had a negative correlation with weight gain, but the changes in glycosuria, appetite scores and the frequency of hypoglycaemia did not correlate with weight gain. Glycaemic control did not correlate with weight change but tended to correlate with fat mass increase (p = 0.064; r = -0.51). An increase in the activity levels between 3 and 6 months correlated with decreasing fat mass (p = 0.037; r = -0.74). The changes in the appetite scores had a negative correlation with fat mass gain (p = 0.035; r = -0.61). The changes in lean body mass correlated with protein and total energy intake (p = 0.007, r = 0.85 and p = 0.003, r = 0.73 respectively). The changes in leptin levels correlated with weight gain. CONCLUSIONS: The lipogenic effect of insulin with subsequent increase in fat mass may be the primary cause of this weight gain that can be attenuated by the increases in the activity levels. The negative correlation of energy intake and appetite scores with fat mass gain suggests that they do not play a significant role in fat mass gain whereas energy intake did correlate with lean body mass gain.     

Long‐term outcome of a covered vs. uncovered transjugular intrahepatic portosystemic shunt in Budd–Chiari syndrome

Background: The clinical outcome of a covered vs. uncovered transjugular intrahepatic portosystemic shunt (TIPS) for patients with Budd–Chiari syndrome (BCS) is as yet largely unknown. Objectives: To compare patency rates of bare and polytetrafluoroethylene (PTFE)‐covered stents, and to investigate clinical outcome using four prognostic indices [Child–Pugh score, Rotterdam BCS index, modified Clichy score and Model for End‐Stage Liver Disease (MELD)]. Methods: Consecutive patients with BCS who had undergone TIPS between January 1994 and March 2006 were evaluated in a retrospective review in a single centre. Results: Twenty‐three TIPS procedures were performed on 16 patients. The primary patency rate at 2 years was 12% using bare and 56% using covered stents (P=0.09). We found marked clinical improvement at 3 months post‐TIPS as determined by a drop in median Child–Pugh score (10–7, P=0.04), Rotterdam BCS index (1.90–0.83, P=0.02) and modified Clichy score (7.77–2.94, P=0.003), but not in MELD (18.91–17.42, P=0.9). Survival at 1 and 3 years post‐TIPS was 80% (95% CI: 59–100%) and 72% (95% CI: 48–96%). Four patients (25%) died and one required liver transplantation. Conclusions: A transjugular intrahepatic portosystemic shunt using PTFE‐covered stents shows better patency rates than bare stents in BCS. Moreover, TIPS leads to an improvement in important prognostic indicators for the survival of patients with BCS.     

Transjugular intrahepatic portal-systemic shunt in the treatment of refractory ascites: Effect on clinical,renal, humoral,and hemodynamic parameters

Seventeen cirrhotics with refractory ascites were treated with transjugular intrahepatic portosystemic shunt (TIPS) and followed for 15.5 ± 3.4 months. Five patients died, four within 3 months after TIPS (hepatocellular failure) and one after 22 months (cholangiocarcinoma). Six patients received transplants 1 to 10 months after the procedure. Actuarial survival at 6, 12, and 24 months was 75%, 75%, and 63%, respectively. Portosystemic venous pressure gradient decreased by 46% at 1 month and by 38% at 7 to 12 months. Eight patients presented 18 stenoses 1 to 18 months after TIPS. Twelve stenoses required balloon dilatation. Tense ascites was present before TIPS in 100% of the patients, whereas it was mild or absent in 56% at 1 month, in 66% at 3 to 6 months, in 57% at 7 to 12 months, and in 100% at 24 months after TIPS. Requirements for diuretics and paracentesis decreased after TIPS (P < .001, both). One month after TIPS, urinary and fractional sodium excretion increased (P < .001, both), plasma renin activity, plasma aldosterone (P < .005, both), and plasma norepinephrine (P < .05) decreased and cardiac output (P < .01) increased, systemic vascular resistances (P < .005) decreased, and arterial pressure did not change. Acute hepatic encephalopathy was frequent early after TIPS but was responsive to treatment and caused no long-term disability. In conclusion, TIPS is useful in the treatment of refractory ascites through lowering portal pressure and improving renal sodium excretion. This effect could be attributable to an increase in effective blood volume causing deactivation of vasopressor systems.     

Increase of serum estradiol in cirrhotic men treated by transjugular intrahepatic portosystemic stent shunt

BACKGROUND/AIMS: Liver cirrhosis is frequently associated with sexual dysfunction and hormonal abnormalities. To evaluate the effect of portosystemic shunting on sex steroid serum concentrations, a prospective study was performed in cirrhotic patients treated consecutively and electively by transjugular intrahepatic portosystemic stent shunt (TIPS). METHODS: In 27 patients with liver cirrhosis we measured serum levels of testosterone (T), sexual hormone binding globulin (SHBG), luteinizing hormone, follicle-stimulating hormone, dehydroepiandrosterone sulfate, androstenedione (A), estradiol (E2), 17-OH-progesterone and the T/SHBG ratio before and 3 months after TIPS. RESULTS: In men (n = 17) 3 months after TIPS, A and E2 significantly increased, with mean serum levels rising from 4.4 +/- 2.5 to 5.6 +/- 2.9 ng/ml (P = 0.04) and from 27 +/- 9 to 40 +/- 19 pg/ml (P = 0.003), respectively. In contrast to A the increase of E2 persisted at 9 and 15 months after TIPS. Erectile dysfunction increased from 30% before TIPS to 70% after TIPS. In women (n = 10) A and E2 levels did not change significantly after TIPS. CONCLUSIONS: TIPS aggravated hormonal dysbalance of sex steroids in favor of estrogens (hyperestrogenism) in men.     

Low-dose growth hormone treatment combined with diet restriction decreases insulin resistance by reducing visceral fat and increasing muscle mass in obese type 2 diabetic patients

OBJECTIVE: To evaluate the effects of low-dose growth hormone (GH) therapy combined with diet restriction on changes in body composition and the consequent change in insulin resistance in newly-diagnosed obese type 2 diabetic patients. DESIGN: Double-blind and placebo-controlled trial of 25-kcal/kg IBW diet daily with GH (n=9; rhGH, 0.15 IU/kg body weight/week) or placebo (n=9) for 12 weeks. SUBJECTS: Eighteen newly-diagnosed obese type 2 diabetic patients (age 42--56 y, body mass index 28.1+/-2.7 kg/m(2)). MEASUREMENTS: Body composition and fat distribution parameters (by bioelectrical impedance analyzer and CT scans), serum IGF-1; serum glucose, insulin and free fatty acid (FFA) during oral glucose tolerance test (OGTT); HbA(1c); serum lipid profiles; and glucose disposal rate (GDR) by euglycemic hyperinsulinemic clamp at baseline and after treatment. RESULTS: The fraction of body weight lost as fat lost was significantly greater (0.98+/-0.39 vs 0.52+/-0.32 kg/kg, P<0.05) and visceral fat area was decreased more in the GH-treated group compared to the placebo-treated group (27.9 vs 21.6%, P<0.05). Lean body mass and muscle area were reduced in the placebo-treated group, whereas an increase in both was observed in the GH-treated group. GDR the was significantly increased in only the GH-treated group (4.67+/-1.05 vs 6.95+/-0.91 mg/kg/min, P<0.05). The GH-induced increase in GDR was positively correlated with the decrease in the ratio of visceral fat area/muscle area (r=0.588, P=0.001). Serum glucose levels and insulin- and FFA-area under the curve during OGTT and HbA(1c) were significantly decreased after GH treatment. LDL-cholesterol level was decreased in only the GH-treated group. CONCLUSION: Low-dose GH treatment combined with dietary restriction resulted not only in a decrease of visceral fat but also in an increase of muscle mass with a consequent improvement of the insulin resistance observed in obese type 2 diabetic patients.